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Using Taproot And FROST To Improve Bitcoin Privacy – Bitcoin Magazine

Posted on October 19, 2022 by Danzig

This is an opinion editorial by Dan Gould and Nick Farrow. Gould is a developer who worked on TumbleBit, PayJoin and Chaincase App and has been sponsored by Human Rights Foundation and Geyser Grants. Farrow is an Australian Bitcoin engineer best known for his open source payment processor SatSale.

Hey, I just got an invite to this hackathon in Malaysia, said Evan Lin, interrupting my flow over my laptop in the Taipei Hackerspace. That sounds magic, I snapped back. Can I come?

Id been smacking my head on the desk for weeks. Lin had been tearing apart my idea of what bitcoin privacy was. Its a private event, not your typical hackathon. I can ask.

One flight, two weeks, and six minutes of voice message logistics later, we were walking down durian-lined streets of Kuala Lumpur, Malaysia, with Lloyd Fournier, ruminating over a shared passion to make bitcoin privacy stick. Now we were a team. We set out to upgrade Fedimint using half-polished cryptography, some scribbled-down notes, and then demo it at the first-ever Malaysian BitDevs meetup five days later.

Fournier had joined Nick Farrow to develop FROST, a new threshold cryptography that takes advantage of Taproot, in the months prior. Being a fountain of Bitcoin human resources, Fournier had also been working closely with Lin who is a Bitcoin Dev Kit (BDK) contributor. He and I had spent the last few weeks upgrading PayJoin privacy under fluorescent lights during the wee hours in Taipei, Taiwan, so wed established trust to jump in the deep end on a project together. Fourniers invitation was a step to the edge. To demonstrate the cutting edge cryptography to the world, we had to put FROST in an app. Fedimint had everyones eyeballs for its new threshold custody model. It was fit for the quest.

Self-custody is a novel, scary concept for most people. So many people store bitcoin in third-party custody on exchanges, leaving them exposed to censorship and indecent surveillance. Federated mints offer a third way: A federation of known guardians keep community funds safe. So how does it work?

Anyone can send bitcoin to a Fedimint in exchange for E-cash tokens. The guardians share custody of the communitys bitcoin in a multisignature wallet. The E-cash tokens are just some data: blind signatures redeemable for some amount of bitcoin later. Theyre superpowered banknotes. Submit a Lightning invoice and your E-cash tokens to peg out. You could get E-cash in a text and have the federation reissue signatures so nobody else can take it. The signatures are blinded, so it can be redeemed in total anonymity. Anyone can send E-cash to a Fedimint to get bitcoin.

In order to share custody between guardians, Fedimint uses legacy Bitcoin Script-based multisignature addresses. A threshold number of guardians sign in order to transfer funds. These funds are easy to spot on the blockchain since Script multisig writes the number of signers and the total number of guardians to the blockchain for anyone to see. Even though E-cash is anonymous, surveillance companies could identify peg-ins, peg-outs and cluster community funds. By harnessing Bitcoins latest upgrade, Taproot, our team solved this privacy issue by switching Script multisig to FROST.

FROST (Flexible Round Optimized Schnorr Threshold) is a powerful new kind of multisig that aggregates the key shares of federation members into a joint FROST key. To spend under this key, a threshold number of members must each produce a signature share. The shares are then combined to form a single signature that is valid under the joint FROST key. Members coordinate off chain. FROST transactions are indistinguishable from regular single-party Taproot spends, and so stop the creepy surveillance. On top of that, FROST allows for flexible federations, allowing new guardians to join without coordinating every member of the federation to generate new keys again.

Our first step was to understand how the federation reached a consensus each signing round. Fedimints consensus algorithm can tolerate bad behavior for up to a third of the federation and still reach consensus. It took a day on the white board to decode the consensus algorithm and another to configure the initial FROST key generation.

Coming to Fedimint consensus (picture supplied by authors)

We cheated key generation by doing it all in a single trusted devices memory. In best practice, a two-round ceremony keeps an individuals secret shares of the joint FROST key which only ever exists on that individuals device. The overall secret is never reconstructed.

We tested a peg-in transaction before we modified Fedimint wallet code and got perplexed. Because of a limitation of blind signatures, Fedimint E-cash tokens (akin to CoinJoin outputs), are limited to preset denominations so that each E-cash token transfer has an anonymity set. Waiting and waiting and waiting, Lin laughed that we must have messed something up.

Turns out, standard note denominations we set required the mint to generate around 300,000 signatures to issue enough E-cash to cover the peg-in amount. There are proposals to fix this by using anonymous credentials instead. We reset the mint to use much higher default denominations since we were just testing. Hackathons are for hacks, after all.

In a stroke of good luck, Bitcoiner Malaysia had just formed and was primed for their first event. Between the four of us hackers, a host of the largest Chinese bitcoin podcast and the scholar on track to earn the first Bitcoin Ph.D. in Malaysia, we planned to show our proof-of-work at BitDevs at the end of the week.

Our hardest task remained ahead of us: federated signatures. To produce a FROST share, signers must agree to common randomness, called nonces. In the case of Fedimint, the signers use consensus to agree on a unique nonce for each federation member joining a signing session. Then signing participants aggregate shares into a complete signature.

While we drafted our live demo for the meetup, we managed to get some nonce sharing semi-working and fixed some fee bugs too. Despite our hard work, dinner rolled around before our code worked. We crossed the threshold into the deepest hackathon territory huddled around the TV for triple-paired programming in Farrows hotel room.

With our tapwaters ready and Unreal Tournament soundboard cranked up, Fournier sat at the keyboard, while we hurled bug fixes, variable names and commands from the back seat. 1:30 a.m. rolled around and our eyelids were heavy. A few taps later, just like magic, the peg-out worked. Each signer would receive signature shares from the others and redeem anons E-cash in exchange for bitcoin. Flawless Victory rang out of the soundboard. We cheered in disbelief.

Except it did not work. The next day we ran the code and saw problems straight away. We only got lucky the night before. It worked only once out of three or four attempts. We combed over hackathon-quality code for hours. Well after lunch, we still worried wed have to cram in another late night. To our avail, we found the problem: a classic indexing error. At 5:00 p.m. FROSTimint was ready to present.

Once we circled up for BitDevs, locals took a self-described support group format for introductions. Fournier brought us back to reality with the technical. The inaugural meetup deliberated the future and foibles of custodians with delight. How would we choose guardians? Can they hold fractional reserves? Most importantly, how can my laksa noodle soup shop transcend fiat by using Fedimint?

This is a guest post by Dan Gould and Nick Farrow. Opinions expressed are entirely their own and do not necessarily reflect those of BTC Inc. or Bitcoin Magazine.

Originally posted here:

Using Taproot And FROST To Improve Bitcoin Privacy - Bitcoin Magazine

Increasing participation in the EMBO Programmes across Europe – EurekAlert

Posted on October 19, 2022 by Danzig

Heidelberg, 18 October 2022 EMBO launches further funding and support schemes for life scientists at all career stages in eleven countries. The schemes include grants for researchers displaced by the military invasion in Ukraine or other armed conflicts.

Until the end of 2024, life scientists in or going to Croatia, Czech Republic, Estonia, Greece, Hungary, Italy, Lithuania, Luxembourg, Poland, Slovenia, and Trkiye (Turkey) can apply for the schemes. These countries are member states of the EMBC (European Molecular Biology Conference), the intergovernmental organization that funds the EMBO Programmes. The initiative aims to increase participation of scientists from across Europe in the programmes, especially in countries that currently benefit less from the programmes.

The new schemes and support offerings are:

These new schemes and support offerings are in addition to those launched previously:

Details of all schemes and offerings, including eligibility criteria and the application process, are availablehere.

All these schemes and support offerings are funded with means from EMBC.

Disclaimer: AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert system.

See the article here:

Increasing participation in the EMBO Programmes across Europe - EurekAlert

A Decade of Breast Cancer at the Molecular Level: Pioneering Personalized Medicine – Targeted Oncology

Posted on October 19, 2022 by Danzig

Breast cancer treatment options have significantly expanded in the past decade, welcoming new classes of agents as well as treatments directed at specific patient populations (TIMELINE).

Many believe that these advancements in breast cancer care over the past 10 years owe much to the increased understanding of molecular factors contributing to breast cancer pathogenesis and heterogeneity.1-3

In looking back at the past decade of targeted therapy in breast cancer, Targeted Therapies in Oncology (TTO) spoke with 2 medical oncologists with extensive expertise in breast cancer about how biomarker advancements have transformed the practice of breast cancer management.

I think its fair to say that breast cancer in particular has led the way in molecular therapeutics in oncology, Dennis J. Slamon, MD, director of clinical/translational research at the UCLA Jonsson Comprehensive Cancer Center, told TTO. In part, thats because of all the investment that was made in research [and] because of defi ning this disease not just at a tissue level, but at a molecular level.

Classification of breast cancers into not just hormone receptor and HER2 positivity or negativity, but also into the luminal/basal subtypes has helped to identify treatments that may be more helpful for large groups of patients.1,3 For example, patients with basal-like disease, which is about 15% to 20% of all breast cancers, have triple-negative breast cancer (TNBC) and a poor prognosis. These patients tend to be responsive to chemotherapy treatment.1

The fact that molecular targets did not consistently translate to all breast cancers has become a key underpinning of our understanding of cancer.1 Not all patients benefi t from molecularly targeted treatments. For instance, HER2-positive breast cancer only accounts for about 25% of all breast cancer cases, thus HER2-targeted therapies may only benefi t 25% of all patients with breast cancer.

The same story is coming up again and again, not necessarily the same genes or the same targets or the same pathways, but the fact that there is a diversity of these diseases thats far beyond what we used to use to classify cancers by the tissue in which they arose, Slamon said.

Our understanding of cancer as a potentially more complex disease than previously supposed, began to develop well before 2012, explained Slamon.

That started in breast cancerbefore molecular medicine, as far back as 1899 or 98, when a surgeon recognized the fact that this disease occurred in women and the fact that it may have some hormonal component, said Slamon.4 After we found HER2, the methods of dissecting a tumor molecularly became much more sophisticated and widespread in their use and now, today, there are 14 molecular subtypes of breast cancer. And that is the underpinning of how breast cancer has led the way [in determining that patients with breast cancer] should not be treated with a one-size-fits-all approach. They should be treated with therapeutics that are directed to the appropriate subtype or the class in which they sit.

These molecular subtype characterizations have also shaped the therapeutic strategies within different breast cancer settings. Just thinking about advances in targeted therapies and how we use them to treat breast cancer in the last decade, I separate it into 2 categories1 is how we treat localized breast cancer,when our goal is to cure the cancer, so stages I to III. Most patients are being diagnosed with those earlier stages of breast cancer, Marina Sharifi , MD, PhD, assistant professor and medical oncologist at the University of Wisconsin Carbone Cancer Center, told TTO.

I think one of the major themes over the last 10 years for these nonmetastatic breast cancers is what I refer to as right-sizing therapy. We know that some of the women who have these early breast cancers can have recurrence down the road and we want to try and prevent that. So, 10 to 15 years ago, all of those women got chemotherapy, but even back then we knew that not every woman needs chemotherapy, and we knew that there were some breast cancers that could potentially benefit from more targeted types of therapies. But in the past 10 years, there have been a few developments that have allowed us to determine which women need chemotherapy and which women we can safely avoid exposing to the [adverse] effects of chemotherapy, said Sharifi.

This new prognostic ability has been fueled by advances in genomic testing.5,6 In addition to hormone receptors and molecular subtypes, other prognostic biomarkers that have been incorporated into practice include transcriptomic and proteomic levels and Ki-67 levels. Other biomarkers utilize combinations of genes to determine potential responses to treatment as well as the possibility of recurrence.

And more recently, research has turned to the use of circulating DNA and circulating tumor cells to help identify further prognostic and predictive bbiomarkers for patients with breast cancer.6

Specifically, for estrogen-driven (estrogen receptor [ER] positive) breast cancers, which are the most common type of breast cancer, we have genomic tests that are now used routinely to help us identify women who can safely avoid chemotherapy with that type of breast cancer. Both the MammaPrint and the OncoType DX are genomic tests that we know are effective in identifying which women do need chemotherapy to help maximize their chances of cure and which women have lower-risk breast cancers where the chemotherapy actually wont help them because they dont need it.7,8 That has been a huge development in the fi eld in the last 10 yearsto go from knowing that these tests were out there but not having that confirmation that we know that they predict chemotherapy benefit to having 2 major trials come out in the last 10 years that demonstrate that they can predict chemotherapy benefit, both in women who have those ER-positive breast cancers without lymph node involvement and also women who have ER-positive breast cancer with lymph node involvement. That has been a major advance for the most common type of breast cancer thats diagnosed across the country.9,10

Both the TAILORx (NCT00310180) and RxPONDER (NCT01272037) trials validated the usefulness of the 21-gene Oncotype DX recurrence score assay in patients with hormone receptorpositive, HER2-negative breast cancer. The TAILORx trial showed that among patients with node-negative disease, those with an intermediate Oncotype DX score, or intermediate risk of recurrence, could benefit from treatment with endocrine therapy alone and avoid receiving chemotherapy. Younger patients (.50 years) with a recurrence score of 16 to 25 still showed some benefit from the combination of chemotherapy and endocrine therapy.9 I n R xPONDER, adjuvant chemotherapy use was not considered necessary in most postmenopausal women with node-positive disease and recurrence scores between 0 and 25. Alternatively, premenopausal women were more likely to benefit from adjuvant chemotherapy.10

On the fl ip side, said Sharifi , somehave high-risk TNBC or high-risk HER2-positive breast cancer, those are types of breast cancer where historically we have struggled to cure women. There weve had a number of different advances. In TNBC, weve had the introduction of immunotherapies into our treatment. The KEYNOTE-522 trial [NCT03036488] showed that if wecombine pembrolizumab [Keytruda] with chemotherapy, that has significantly increased the number of women were able to cure of that higher-risk TNBC.11

Approval of neoadjuvant pembrolizumab in combination with chemotherapy for patients with high-risk, early-stage TNBC followed by single-agent adjuvant pembrolizumab by the FDA in 2021 was a signifi cant advancement for the treatment of patients with TNBC.12 Data from the KEYNOTE-522 trial were considered practice changing early on, showing a pathological complete response in 64.8% of patients treated with the regimen.11

Likewise, for HER2-positive breast cancer, we have seen the development of multiple drugs that target HER2, from trastuzumab [Herceptin] and pertuzumab [Perjeta], to ado-trastuzumab emtansine [T-DM1; Kadcyla], that have increased the number of women who were able to cure of their HER2-positive breast cancers, Sharifi said.

Slamon also commented on the proliferation of HER2-targeting therapies in addition to the expansion of other types of targeted agents, benefi tting patients in the TNBC space. [Since] our initial fi nding of HER2 and trastuzumab, now theres a ton of HER2 targeting trastuzumab deruxtecan [Enhertu] and emtansine [Kadcyla], margetuximab [Margenza]the list goes on and on of anti- HER2 therapeutics. Then there are new therapeutics for TNBC; they look at the TROP-2 target on tumor cells, and sacituzumab govitecan [Trodelvy] is the new therapeutic for that.13 As we identify new targets that we can approach with an antibody thatll attach to it, [it could be possible to] make an antibody- drug conjugate [ADC] to allow that antibody to go right to the target protein on the tumor cell and have it released internally and that takes away the systemic effect of the chemotherapy and delivers it right into the cell. Thats a whole new strategy thats coming into its own in a big way now, Slamon told TTO.

The phase 3 ASCENT study (NCT02574455) showed that sacituzumab produced a PFS and overall survival (OS) benefi t over physicians choice of chemotherapy in patients with relapsed or refractory metastatic TNBC. The median PFS with sacituzumab was 5.6 months compared with 1.7 months with chemotherapy. Median OS was 12.1 months with the ADC and 6.7 months with chemotherapy.13

The emergence of these newer targeted therapies has permitted a risk-based tailoring of neoadjuvant and adjuvant therapies in the non-metastatic breast cancer space, observed Sharifi . Another major development over the last 10 years, particularly for the [patients with] TNBC and HER2-positive breast cancers, is a shift towards neoadjuvant chemotherapy, which allows us to identify women with higher risk of recurrence after our standard pre-operative chemotherapy, and then add additional therapy after surgery to reduce their risk. For instance, that is how ado-trastuzumab emtansine is used in HER2-positive breast cancer, and there are other targeted options in this space, including olaparib [Lynparza] for women with germline BRCA mutations, she said.

We have also made great strides in precision oncology in the metastatic breast cancer space, with an expansion of different types of targeted approaches, including mutation-targeted inhibitors, immunotherapy, and ADCs. While all of these developments have helped patients live longer and better with metastatic breast cancer, I think ADCs are the most game-changing new development for treating metastatic breast cancer, Sharifi told TTO. As an example, the ADC trastuzumab deruxtecan, is a HER2-targeting agent [encompassing] trastuzumab linked to a chemotherapy that was initially found to be extremely effective for HER2-positive metastatic breast cancer, even in women who have had multiple prior treatments with different other agents. Even more importantly, however, it has recently been shown to be effective also in women who have low HER2 expression, who would previously have been classifi ed as HER2 negative.14 This has dramatically expanded the group of women with metastatic breast cancer who can benefit from trastuzumab deruxtecan to include what we are now calling HER2-low breast cancers, which are far more common than HER2-positive breast cancers. So thats been an important advance for us in the ADC space just in the last year, said Sharifi.

Data from the phase 3 DESTINY-Breast04 trial (NCT03734029) showed that patients with low HER2 expression can still possibly benefit from HER2-targeted therapy. The trial demonstrated a median progression-free survival (PFS) of 10.1 months with trastuzumab deruxtecan therapy vs 5.4 months with physicians choice of therapy in patients with HER2-low (IHC 1+/IHC 2+, ISH-) metastatic breast cancer who had received 1 to 2 prior lines of chemotherapy. The median OS was 23.9 months with trastuzumab deruxtecan and 17.5 months with physicians choice of chemotherapy.14 These findings led to the FDA approval of trastuzumab deruxtecan in this disease setting just this year.15

The Importance of Individualization

Turning to mutation-targeted therapies, this has also been an active area in metastatic breast cancer treatment in the past 5 years, including the first FDA approval of a drug targeting PIK3CA mutations, [which] are common in many types of cancer and found in almost half of women who have ER-positive metastatic breast cancer, where the drug alpelisib [Piqray] has been approved for women with this type of mutation, Sharifi told TTO.

Approval for alpelisib in breast cancer was supported by fi ndings from the phase 3 SOLAR-1 trial (NCT02437318), which showed that the PI3K inhibitor in combination with fulvestrant led to a median PFS of 11.0 months vs 5.7 months with fulvestrant in patients with PIK3CA-mutant, HR-positive, HER2-negative advanced breast cancer.16

patient with metastatic breast cancer should be getting molecular profi ling to identify possible targeted therapy options, and many patients will now have ADC treatment options that they may be eligible for at some point in their disease trajectory. For patients with localized breast cancer, I think weve also come a long way in being able to individualize therapy and avoid exposing patients to unnecessary [adverse] effects while also being able to augment treatment for patients who are at higher risk of recurrence and cure more women with this diagnosis, Sharifi said.

The basis of this personalized therapy derived from breast cancer-based research, observed Slamon. The gamechanger clearly was [the molecular advancements]. [When] looking at what is big in oncology, its this appreciation that originated in breast cancer and now has spread throughout the field of human oncology about this molecular diversity defining, a) different subtypes, and b) new potential therapeutic targets or pathways, he said.

Sharifi looks to the continued development of ADCs as a cancer treatment modality. Theres a real untapped well of potential targets that were just starting to explore in terms of developing new ADCs and combining them with targeted and immunotherapy approaches, and I think this will move the bar in how were able to combat treatment resistance, said Sharifi.

Slamons view of the future also comprises targeted strategies : As we identify more targets...therell probably be more and newer, perhaps even better, therapeutics than we have currently. Breast cancer has led this field.

REFERENCES:

1. Bettaieb A, Paul C, Plenchette S, Shan J, Chouchane L, Ghiringhelli F. Precision medicine in breast cancer: reality or utopia? J Transl Med. 2017;15(1):139. doi:10.1186/s12967-017-1239-z

2. Cocco S, Piezzo M, Calabrese A, et al. Biomarkers in triple-negative breast cancer: state-of-the-art and future perspectives. Int J Mol Sci. 2020;21(13):4579. doi:10.3390/ijms21134579

3. Low SK, Zembutsu H, Nakamura Y. Breast cancer: The translation of big genomic data to cancer precision medicine. Cancer Sci. 2018;109(3):497-506. doi:10.1111/cas.13463

4. Beatson GT. On the treatment of inoperable cases of carcinoma of the mamma: suggestions for a new method of treatment, with illustrative cases. Trans Med Chir Soc Edinb. 1896;15:153-179.

5. Hou Y, Peng Y, Li Z. Update on prognostic and predictive biomarkers of breast cancer. Semin Diagn Pathol. 2022;39(5):322-332. doi:10.1053/j.semdp.2022.06.015

6. Nicolini A, Ferrari P, Duff y MJ. Prognostic and predictive biomarkers in breast cancer: past, present and future. Semin Cancer Biol. 2018;52(Pt 1):56-73. doi:10.1016/j.semcancer.2017.08.010

7. Cardoso F, vant Veer LJ, Bogaerts J, et al; MINDACT Investigators. 70- gene signature as an aid to treatment decisions in early-stage breast cancer. N Engl J Med. 2016;375(8):717-729. doi:10.1056/NEJMoa1602253

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A Decade of Breast Cancer at the Molecular Level: Pioneering Personalized Medicine - Targeted Oncology

Developing New Tools to Fight Cancer – Duke University School of Medicine

Posted on October 19, 2022 by Danzig

For decades, medical cancer treatment has generally meant chemotherapy, radiation, or surgery, alone or in combination. But things are changing rapidly. Today, new approaches such as immunotherapies and targeted therapies are becoming available, with many more in research and development. In many cases, the new treatments are more effective, with fewer side effects.

Its an exciting time to be in cancer research and cancer discovery, said Colin Duckett, PhD, professor of pathology, interim chair of the Department of Pharmacology and Cancer Biology, and vice dean for basic science."

Were moving into this era where we have a new set of tools we can use to treat cancer.-Colin Duckett, PhD

Researchers in the Duke Cancer Institute (DCI) and across the School of Medicine are helping to create these new tools, fueled by the knowledge and experience of experts from a wide range of disciplines.

Indeed, cancer research has always been a team-based endeavor at DCI.

DCI was specifically created a decade ago to break down barriers between disciplines to stimulate collaborative research and multidisciplinary interaction, said DCI Executive Director Michael Kastan, MD, PhD, the William and Jane Shingleton Distinguished Professor of Pharmacology and Cancer Biology.

Adding fuel to the fire is the Duke Science and Technology (DST) initiative, which aims to catalyze and support collaborative research in service of solving some of the worlds most pressing problems, including cancer.

The new tools, though varied, all represent advances in personalized cancer medicine. Targeted treatments are chosen based on the genetic signature of a patients tumor. Some immunotherapies take personalization even further, by manipulating a patients own immune cells to create a treatment for that individual alone.

To match treatments to patients, the multidisciplinary Duke Molecular Tumor Board, led by John Strickler, MD, HS11, and Matthew McKinney, MD06, HS06-09, HS10-13, helps providers identify best practices, newly approved treatments, or clinical trials for advanced cancer patients based on genetic sequencing of their tumors.

In precision cancer medicine the right therapy for the right patient at the right time all these things come together, the targeted therapies, the immunotherapy, even standard chemotherapy, all of that is part of precision cancer medicine.-Michael Kastan, MD, PhD

Immunotherapy aims to harness the power of the immune system to fight cancer. That can mean activating the immune system, energizing exhausted immune cells, or helping immune cells find cancer cells by guiding them there or by removing cancers good guy disguises.

Dukes Center for Cancer Immunotherapy supports these efforts by identifying promising basic science discoveries and building teams to translate those ideas into treatments.

"There are so many world-class basic research scientists here making discoveries..."-Scott Antonia, MD, PhD

...discoveries that are potentially translatable as immunotherapeutic strategies, said Scott Antonia, MD, PhD, professor of medicine and the centers founding director. Thats what motivated me to come to Duke, because of the great opportunity to interact with basic scientists to develop new immunotherapeutics and get them into the clinic.

Antonia believes immunotherapy has the potential to revolutionize cancer treatment, but more work remains to be done to realize its promise. The proof of principle is there, he said, but still only a relatively small fraction of people enjoy long-term survival. If we can hone immunotherapeutic approaches, thats our best opportunity.

Among the most exciting immunotherapy work being facilitated by the center involves removing a patients own T cells (a type of lymphocyte), manipulating them in the lab to make them more effective against tumors, then injecting them back into the patient.

T cells can be manipulated in the lab in a number of different ways. In one approach, called CAR T-cell therapy, the T cells are engineered with an addition of synthetic antibody fragments that bind to the patients tumor, effectively directing the T cells directly to the tumor cells.

In another approach, called tumor-infiltrating lymphocyte (TIL) adoptive cell therapy, the subset of a patients T cells that have already managed to find their way into the tumor are extracted and then grown to large numbers before being returned to the patient. Antonia and his colleagues recently published a paper demonstrating the effectiveness of TIL expansion in lung cancer. Were now doing the preparative work to develop clinical trials using this approach in brain tumors, and our intention is to expand into many other cancers as well, he said.

Antonia points out that innovations in CAR T-cell therapy and TIL therapy happening at Duke are possible because of collaborations with scientists in an array of disciplines, including antibody experts like Barton Haynes, MD, HS73-75, the Frederic M. Hanes Professor of Medicine, and Wilton Williams, PhD, associate professor of medicine and surgery, at the Duke Human Vaccine Institute, and biomedical engineers like Charles Gersbach, PhD, the John W. Strohbehn Distinguished Professor of Biomedical Engineering at the Pratt School of Engineering.

Furthermore, clinical trials for these kinds of cellular therapies require special facilities to engineer or expand the cells, which are provided by Dukes Marcus Center for Cellular Cures, led by Joanne Kurtzberg, MD, the Jerome S. Harris Distinguished Professor of Pediatrics, and Beth Shaz, MD, MBA, professor of pathology. Its been a very productive collaboration highlighting how Duke is uniquely positioned to develop immunotherapeutic strategies, Antonia said.

Targeted therapies exploit a tumors weak spot: a genetic mutation, for example. The benefit is that the treatment kills only cancer cells and not healthy cells. The prerequisite is knowing the genetics and biology of the specific tumor, no simple task.

Trudy Oliver, PhD05, who joined the Department of Pharmacology and Cancer Biology faculty as a Duke Science and Technology Scholar, studies cancer development and the biology of tumor subtypes, particularly squamous cell lung cancer and small cell lung cancer.

Even within small cell lung cancer, there are subsets that behave differently from each other, she said. Some of the treatments shes identified are in clinical trials

Our work suggests that when you tailor therapy to those subsets, you can make a difference in outcome.-Trudy Oliver, PhD'05

Some of the treatments shes identified are in clinical trials.

Sandeep Dave, MD, Wellcome Distinguished Professor of Medicine, is leading an ambitious project to analyze the genomics of the more than 100 different types of blood cancer. His project will streamline the diagnosis of blood cancer and uncover potential therapy targets.

All cancers arise from genetic alterations that allow cancer to survive and thrive at the expense of the host, he said. These genetic alterations are a double-edged sword they allow these cancer cells to grow, but on the other hand they do confer specific vulnerabilities that we can potentially exploit.

Dave said his background in computer science, genetics, and oncology helped him as he designed the project, which uses huge datasets.

Weve done the heavy lifting in terms of tool development and methodology, which is ripe to be applied to every other type of cancer."-Sandeep Dave, MD

Cancer disparities are caused by a complex interplay of elements, including access to health care and other resources, institutional barriers, structural racism, and biology, such as ancestry-related genetics. For example, some genetic biological factors and social elements contribute to disparities in many types of cancer.

Cancer treatment is approaching this personalized space where patients are no longer treated with a one-size-fits-all paradigm."-Tammara Watts, MD, PhD

"Its becoming increasingly apparent that there are differences in outcome with respect to race and ethnicity, said Tammara Watts, MD, PhD, associate professor of head and neck surgery & communication sciences, and associate director of equity, diversity, and inclusion at DCI. The very broad hypothesis is that there are genetic ancestry-related changes that may play a critical role in the disparate clinical outcomes we see every day in our cancer patients.

For example, self-identified white patients with throat cancer associated with the human papilloma virus (HPV) have better outcomes compared to self-identified Black patients, even when controlling for elements such as health care access, education, and socioeconomic status.

Watts is collaborating with bioinformatics experts at DCI to try to identify significant differences in gene expression among the two groups.

Im trying to tease out differences that may be impactful for disadvantaged patients based on race and ethnicity, she said. But there could be differences that emerge that could be useful for designing targeted treatments for a broad group of patients.

Thats because a targeted treatment for a particular genetic expression that might occur more commonly in Black people would help all patients with that expression, regardless of race or ethnicity.

Watts is far from alone in doing cancer disparity research at DCI. Tomi Akinyemiju, PhD, associate professor in population health sciences, uses epidemiology to study both biological factors and social elements that contribute to disparities in many types of cancer.

Jennifer Freedman, PhD, associate professor of medicine, Daniel George, MD92, professor of medicine, and Steven Patierno, PhD, professor of medicine and deputy director of DCI, are studying the molecular basis for why prostate, breast, and lung cancer tend to be more aggressive and lethal in patients who self-identify as Black. Patierno, who has been a national leader in cancer disparities research for more than 20 years, leads the Duke Cancer Disparities SPORE (Specialized Program of Research Excellence), funded by the National Cancer Institute. The SPORE grant supports these researchers as well as other DCI teams working on cancers of the breast, lung, stomach, and head and neck.

One of the things that impresses me is that [cancer disparities research] is a high priority within DCI, said Watts, who joined the faculty in 2019. These groups are actively engaged and collaborating and asking the questions that will drive change for patients who have worse outcomes that are related to ancestry.

Even better than a cancer cure is avoiding cancer altogether.

At DCI, Meira Epplein, PhD, associate professor in population health sciences, and Katherine Garman, MD02, MHS02, HS02-06, HS09, associate professor of medicine, are looking to decrease the incidence of stomach cancer by improving detection and treatment of the bacteria Helicobacter pylori, which can set off a cascade leading to stomach cancer. Epplein and Garman, also funded by the Duke Cancer Disparities SPORE grant, hope their work will reduce disparities because H. pylori infections and stomach cancer are both more prevalent among African Americans than whites.

When preventing cancer isnt successful, the next best thing is to detect and treat early. A relatively new concept in cancer care is interception, which means catching cancer just as, or even just before, it begins.

The point is to prevent it from progressing to full blown malignancy, said Patierno. In other words, stop the cancer from getting over its own goal line.

Patierno envisions a future where patients with pre-cancerous conditions or early cancer could take a pill to halt cancer development without killing cells in other words, a non-cytotoxic treatment, unlike standard chemotherapy.

We know its there, but were not going to poison it or burn it or cut it out because all of those have side effects. Were going to find a non-cytotoxic way to prevent it from progressing. Thats the goal.-Steven Patierno, PhD

Read About Alumni Making a Differencein Cancer Research and Care:

Changing theStatus Quo: Lori Pierce MD'85

Treatingthe WholePerson:Arif Kamal, MD,HS12, MHS15

Targetingthe Seeds ofCancer Growth:Eugenie S. Kleinerman, MD75, HS75

A DiscoveryThat Comes Outof Nowhere:Bill Kaelin, BS79, MD82

Story originally published in DukeMed Alumni News, Fall 2022.

Skin and brain cancers: New discovery may help improve treatment – Medical News Today

Posted on October 19, 2022 by Danzig

Cancer is a disease where the cells of the body grow uncontrollably and can invade other parts of the body. These cells can destroy healthy cells by blocking essential nutrients and changing the function of organs.

Cancer impacts millions of people in the United States alone. Treatment options have improved in recent decades, but many underlying mechanisms of cancer remain unknown.

A recent study published in Nature Structural & Molecular Biology explored a specific molecular pathway that may underlie several cancer types, including basal cell carcinoma of the skin, which is the most common form of skin cancer, and medulloblastoma, the most common brain tumor affecting children.

Understanding how this pathway works could open the door for new cancer treatment options.

In 2020, cancer was the second leading cause of death in the U.S. Experts are still working to understand what triggers and contributes to cancer development and growth.

Researchers have collected some data on risk factors for specific cancer types so that people can understand their risks and work to take preventative steps.

Treatment options for cancer have increased in recent decades, with more targeted therapies becoming available that cause less damage to the rest of the body. Cancer treatment can involve a combination of several treatments, such as radiation, immunotherapy, hormone therapy, or surgery.

To develop new treatments with greater success rates and fewer side effects scientists are working to better understand the biological mechanisms which can increase an individuals risk of developing the disease.

Studying what happens at the cellular and molecular levels can identify new targets for treatment.

Researchers involved in this study looked at a key signaling pathway in organ development, known as the Hedgehog pathway. Underactivity of this pathway has been linked to birth defects, while overactivation has been shown to drive certain cancers.

Study author Dr. Benjamin Myers, assistant professor in the Department of Oncological Sciences at the Huntsman Cancer Institute, University of Utah School of Medicine, explained the underlying mechanism of interest in this current study.

This study was focusing on a system in our bodies known as a signaling pathway. A signaling pathway is a bit like a telephone wire in our cells that helps relay important information from the outside of the cell to the inside, he explained.

The signaling pathway that we are studying, known as Hedgehog, is very important in helping our tissues and organs develop correctly. Also, errors in this signaling pathway can lead to birth defects or cancers, including some fairly common skin tumors and pediatric brain tumors, the study author further noted.

Researchers focused on the Smoothened protein (SMO). They found that the SMO protein physically blocks a key signaling enzyme in the Hedgehog pathway called the PKA catalytic subunit (PKA-C).

The lack of PKA-C causes the release of gene-regulating proteins which are usually inhibited and the promotion of the Hedgehog pathway.

Dr. Myers explained:

For many years, scientists knew that Hedgehog played all these critical roles in development and disease but didnt understand how the actual telephone wire worked what type of molecular signal was encoded, and how did it travel from the outside of the cell to the inside? Our study helps to resolve this longstanding mystery by revealing the underlying molecular basis for how Hedgehog signals travel along this telephone wire.

Dr. Santosh Kesari, director of neuro-oncology at Providence Saint Johns Health Center and chair of the Department of Translational Neurosciences and Neurotherapeutics at Saint Johns Cancer Institute in Santa Monica, CA, who was not involved in this study, offered a further explanation to Medical News Today.

This study elaborates on the mechanism of how these tumors grow when a signal on the surface of the tumor cell initiates a signaling program that makes these grow uncontrolled. They found a novel mechanism whereby hedgehog signaling goes through PKA-C to activate the pathway. This opens up a new understanding and possible a new drug target, he told us.

The study offered significant findings and is a critical step towards understanding an underlying mechanism in particular cancer development. However, it only utilized mouse and cellular models, which can only provide a certain level of information. Further research is going to be essential when it comes to translating this information into clinical practice.

Dr. Kesari noted: Future research will focus on confirming this signaling pathway and how it affects tumor growth. This pathway can be looked at as a target for drug development to try to prevent this activation of tumor growth program.

Ideally, the data from this study can help to forward the development of more targeted cancer treatments. Dr. Myers was optimistic about what they had found and what it could mean for the future.

Our study helps to explain at a molecular level how errors in Hedgehog signaling can lead to birth defects or cancer. Having this knowledge help scientists and clinicians understand these diseases at a more fundamental level. In the future, our research may enable new types of drugs to correct the faulty Hedgehog signaling events that occur in cancer and thereby provide therapeutic benefit to cancer patients in the clinic, he said.

This was very difficult in the past due to a lack of knowledge about how the Hedgehog pathway worked at a molecular level, but the insights provided by our study may help to realize this long-term therapeutic goal in the future, added Dr, Myers.

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Skin and brain cancers: New discovery may help improve treatment - Medical News Today

The XBB family of Omicron has landed in the U.S. Here’s what it means for this fall’s COVID wave – Fortune

Posted on October 19, 2022 by Danzig

XBBa new, extremely immune-evasive Omicron variant surging in Singaporehasnt yet been detected in the U.S. But its child has.

XBB.1 was first detected in the U.S. on Sept. 15 and made up 0.26% of cases that were genetically sequenced over the past 15 days, Raj Rajnarayanan, assistant dean of research and associate professor at the New York Institute of Technology campus in Jonesboro, Ark., told Fortune. He cited data from GISAID, an international research organization that tracks changes in COVID and the flu virus.

Only 16 XBB.1 cases have been detected in the U.S. so far, and most have been found in New Yorkconsidered a bellwether state because of its volume of incoming international travelers and robust genetic sequencing capabilities, Rajnarayanan said.

XBB is a combination of two different Omicron spawns. It, along with BQ.1.1, is considered to be the most immune-evasive COVID variant so far, surpassing the immune-evasiveness of shared ancestor BA.5, which was dominant around the globe this summer.

Scientists, including top U.S. infectious disease expert Dr. Anthony Fauci, expect a fall and winter wave of cases in the U.S. that begins to surge in October and peaks in January. Its still unclear which COVID variant may fuel that wave. On Friday the U.S. Centers for Disease Control and Prevention announced that heavyweight Omicron spawn BQ.1 and BQ.1.1 are in the U.S., and quickly rising. With XBB present as well, the scene has been set for a potential battle royal between two formidable variants.

Compared to XBB, XBB.1 features just one small change to the spike protein, which the virus uses to attach to and infect cells. The impact of the alteration is unknown, according to Rajnarayanan.

Its one of multiple XBB offspring being eyed by variant trackers globally that are helping fuel Singapores wavedespite a significantly vaccinated and boostered population.

Rajnarayanan isnt worried about one variant in particular right now, as current Omicron spawn are all picking up similar mutations that confer advantages like increased transmissibility and additional ability to evade immune systems.

Hes keeping a close eye on XBB. But hes keeping a closer eye on BQ.1.1, which, along with parent BQ.1, was estimated to make up more than 11% of cases in the U.S. last weekthis on the first day the two variants were broken out into their own categories from ancestor BA.5.

BQ.1.1 is surging in New York and also rising in European countries like Germany, where Oktoberfest celebrations may have served as super-spreader events. Its extreme immune evasiveness sets it up to be the principal driver of the next U.S. wave in the weeks ahead,Dr. Eric Topol, a professor of molecular medicine at Scripps Research and founder and director of the Scripps Research Translational Institute, tweeted on Friday.

On Thursday, he told Fortune that scientists wont know to what extent it evades vaccine protection, if it does, until it reaches 30% to 50% of cases somewhere.

Its not going to wipe out vaccine efficacy, but it could put a dent in protection against hospitalizations and death, he said.

Both XBB and BQ.1.1 are known to escape antibody immunity, rendering useless monoclonal antibody treatments used in high-risk individuals with COVID. According to a study last month out of Peking Universitys Biomedical Pioneering Innovation Center in China, both escape immunity from Bebtelovimab, the last monoclonal antibody drug that is effective on all variants, as well as Evusheld, which works on some. And both could lead to more severe symptoms, the authors wrote.

The ability of XBB to evade immunity is extreme, approaching the level of immune evasion shown by SARS, a coronavirus that infected thousands and caused nearly 800 deaths in the early 2000s, the authors added.

BQ.1.1 and XBB are so distinct from other Omicron strains that they should be granted new Greek letter names, like Pi or Rho, by the World Health Organization, Topol told Fortune last week.

Whether the two strains eventually battle for dominance in the U.S.or anywhere elseremains to be seen. They may even find themselves sparring in one hostand the result could be a strain that combines the two, Ryan Gregory, a professor of evolutionary biology at the University of Guelph in Ontario, Canada, told Fortune. Or descendants of the two might find themselves battling it out instead.

With the viruss record rate of evolution, the possibilities are seemingly endless.

If people arent boosted and havent been infected in a little while, youre going to see lots of transmission, youre going to see direct competition, Gregory said, speaking of the highly immune-evasive variants. Were basically going to see them both move into whatever hosts are available.

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The XBB family of Omicron has landed in the U.S. Here's what it means for this fall's COVID wave - Fortune

Projects for Progress, two years in | Penn Today – Penn Today

Posted on October 19, 2022 by Danzig

In 2021, three Projects for Progress (P4P) teams set out to improve the quality of life in West Philadelphia: one by addressing the primary care needs of homeless and underserved people, one by revamping the Cobbs Creek Community Environmental Center, and one by addressing the COVID-induced learning gap in elementary school students and educators. An Oct. 17 event celebrated the work of these teams and their 2022 counterparts. Six P4P groups have received awards since the initiatives inception.

First awarded in 2021, the Projects for Progress are managed by Penns Office of Social Equity & Community, which distributed $100,000 each to three teams of Penn students, faculty, and staffworking to promote equity and inclusion in Philadelphia by addressing health care, education, and environmental justice.

For Caroline Watts of the Graduate School of Education, the awards timing was crucial. When the pandemic hit in March 2020, many students in the School District of Philadelphia were out of the classroom for more than a year. A joint team from theGraduate School of Education and the Netter Center for Community Partnerships worked to address this gap, wrapping Netters annual summer programming in an added layer of academic and mental health support. The award also funded school-year support for educators at 15 schools in West and Southwest Philadelphia, including professional development, algebra readiness clubs, and mental health consultation.

With the Projects for Progress award, we were able to put our ideas into action at a time when resources were urgently needed to help students and teachers return to in-person learning, Watts says. This award enabled us to respond to critical learning and development needs and to provide children with a joyful in-person experience after a long period of isolation.

Ricky Brathwaite, a Ph.D. student at the Perelman School of Medicine, is part of a 2022 P4P team that is working to lower the burden of cancer disparities in West Philadelphia. The award provides funding for cancer education and screening kits while helping the team demystify cancer research participation through conversation, all concentrated in West Philadelphia. It helps us change from their community to our community by actively reallocating resources through service to meet people where they are, Brathwaite says.

The group has partnered with other agencies and organizations to extend their reach, and plans to expand their mission beyond colorectal cancer to include HPV testing as new at-home tests become available, in addition to providing free breast and cervical cancer early detection at events with mobile health units. The group is looking to best serve the community with the work we do, Brathwaite says.

The additional groups in the 2022 P4P cohort include the Economic Justice Partnership, which trains first-generation college students, students of color, and high school students to do peer coaching on financial education, and The Public Schools as Equity Infrastructure Studio+, a collaborative partnership working to design and implement public school campus upgrades that embody a new system-wide vision for schools as equity infrastructure.

The 2023 applications will go live on Jan. 17. Applications are due by Jan. 29.

Evelyn Gotlieb, Wharton 2021 undergraduate, concentration in health care management and policy, minor in chemistry

Junduo Liu, College of Arts & Sciences 2022 undergraduate, double major in biochemistry and health & societies, minor in Bbioethics

Michael Hagan, College of Arts & Sciences 2022 undergraduate, major in neuroscience

Ian McCurry, Perelman School of Medicine 2022 doctor of medicine program

Deepti Tantry, College of Arts & Sciences 2022 undergraduate, major in neuroscience, minor in health care management

Mentor:Joseph Teel, Perelman School of Medicine associate professor of clinical family medicine and community health

Bridging Gaps and Building Capacity: Student and Educator Supports for School Reopening in Learning Network 2

Caroline Watts, Graduate School of Education director, Office of School & Community Engagement; senior lecturer, Professional Counseling Programs

Diane Waff, Graduate School of Education professor of practice; director, Philadelphia Writing Project

Zachary Herrmann, Graduate School of Education executive director, Center for Professional Learning

Marsha Richardson, Graduate School of Education senior lecturer, human development & qualitative methods

Regina Bynum, Netter Center for Community Partnershipsdirector of teaching and learning, University Assisted Community Schools

A Collaborative Initiative to Renovate and Optimize the Cobbs Creek Community Environmental Center

Erica DePalma, formerly of the Water Center research program coordinator, Earth and Environmental Science Department

Chinedu Ocek Eke, School of Engineering and Applied Science director for graduate students programming, Office of Diversity, Equity and Inclusion

Anna Balfanz, Netter Center for Community Partnerships senior research coordinator

Cooper Yerby, School of Arts & Sciences 2023 doctoral program in earth and environmental science

The Economic Justice Partnership:

Brian Peterson, director of Makuu: The Black Cultural Center

Khusi Shelat, Wharton 2023 undergraduate, statistics

Soloman Thomas, Wharton 2023 undergraduate, management/entrepreneurship & innovation.

An initiative to lower the burden of cancer in West Philadelphia:

Roderick Brathwaite, Perelman School of Medicine Ph.D. student, cell and molecular biology, cancer biology

Carmen Guerra, Perelman School of Medicine Ruth C. and Raymond G. Perelman Associate Professor of Medicine

Erin Hollander, Perelman School of Medicine MD/Ph.D. student, cell and molecular biology, cancer biology concentration

Claudia Melendez, School of Arts & Sciences 2023 undergraduate, neuroscience/international relations, chemistry minor

Michael Noji, Perelman School of Medicine Ph.D. student, cell and molecular biology, cancer biology concentration

Armenta Washington, Abramson Cancer Center and Perelman School of Medicineresearch coordinator senior, Office of Diversity and Outreach

Public Schools as Equity Infrastructure Studio+:

Anna Balfanz, Netter Center for Community Partnerships Academically Based Community Service coordinator

Ellen Neises, Weitzman School of Design executive director of PennPraxis and Laurie Olin Professor of Practice

Akira Rodriguez, Stuart Weitzman School of Designassistant professor, Department of City & Regional Planning

Elinor Williams, Graduate School of Education Ph.D. student, education policy

Corey Wills, Stuart Weitzman School of Design and School of Arts & Sciencesgraduate student, master of city planning, master of environmental studies

Visit theProjects for Progress websitefor more information,or emailprojectsforprogress@sec.upenn.edu.

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Projects for Progress, two years in | Penn Today - Penn Today

UT Southwestern ranked top health care institution globally for published research by Nature Index – UT Southwestern

Posted on October 19, 2022 by Danzig

DALLAS Oct. 12, 2022 For the third year in a row, UTSouthwestern is ranked as the top health care institution globally by Nature Index for publishing high-quality research inall subjects and in the life sciences.

Joan Conaway, Ph.D.

We are incredibly proud of the outstanding work by our scientists and clinical researchers that is reflected in these Nature Index 2022 rankings, said Joan Conaway, Ph.D., Vice Provost and Dean of Basic Research at UTSW. Our discoveries impact multiple fields in basic science and are making a real difference in developing diagnostic and therapeutic applications for patients at our institution and beyond.

The Nature Index compiles affiliation information from research articles published in 82 premier science journals, providing perspective on high-quality scientific discoveries around the globe.

UTSW also ranked second globally this year among health care institutions in chemistry; among the top 10 in biochemistry and cell biology, earth and environmental, and physical sciences; and among the top 25 in neurosciences. Other peer institutions on the global listings include Massachusetts General Hospital, Mount Sinai Health System, Memorial Sloan Kettering Cancer Center, the University of Texas MD Anderson Cancer Center, and Brigham and Womens Hospital System in the United States; along with the Scientific Institute for Research, Hospitalization, and Healthcare in Italy, the West China School of Medicine/West China Hospital of Sichuan University in China, and Renji Hospital in China.

UTSW's ranking is a testament to the consistent strength and impact of our research community. Our scientists are currently leading about 5,800 research projects with nearly $610 million in support from the National Institutes of Health, the state of Texas, foundations, individuals, and corporations, said W. P. Andrew Lee, M.D., Executive Vice President for Academic Affairs, Provost, and Dean of UTSouthwestern Medical School, who holds the Atticus James Gill, M.D. Chair in Medical Science.

UTSW faculty members have received six Nobel Prizes, and its faculty includes 24 members of the National Academy of Sciences, 17 members of the National Academy of Medicine, 16 members of the American Academy of Arts and Sciences, 14 Howard Hughes Medical Institute Investigators, and three recipients of the prestigious Breakthrough Prize in Life Sciences. The Medical Center houses one of HHMIs 12 principal laboratories nationwide, has four HHMI Faculty Scholars on campus, and has more than 100 early-career researchers, who have come to UTSW through the Medical Centers acclaimed Endowed Scholars Program in Medical Science, subsequently establishing themselves as leaders in their fields.

The UTSW Graduate School of Biomedical Sciences, with more than 1,000 predoctoral and postdoctoral students, educates biomedical students, engineers, clinical researchers, and psychologists. The Graduate School has two Divisions: Basic Science and Clinical Science, which together offer 11 programs leading to the Ph.D. degree Biological Chemistry; Biomedical Engineering; Cancer Biology; Cell and Molecular Biology; Clinical Psychology; Genetics, Development, and Disease; Immunology; Molecular Biophysics; Molecular Microbiology; Neuroscience; and Organic Chemistry. In addition, an M.S. degree and graduate certificate are offered in Clinical Science.

Dr. Conaway holds the Cecil H. Green Distinguished Chair in Cellular and Molecular Biology.

About UTSouthwestern Medical Center

UTSouthwestern, one of the nations premier academic medical centers, integrates pioneering biomedical research with exceptional clinical care and education. The institutions faculty has received six Nobel Prizes, and includes 24 members of the National Academy of Sciences, 17 members of the National Academy of Medicine, and 14 Howard Hughes Medical Institute Investigators. The full-time faculty of more than 2,900 is responsible for groundbreaking medical advances and is committed to translating science-driven research quickly to new clinical treatments. UTSouthwestern physicians provide care in more than 80 specialties to more than 100,000 hospitalized patients, more than 360,000 emergency room cases, and oversee nearly 4 million outpatient visits a year.

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UT Southwestern ranked top health care institution globally for published research by Nature Index - UT Southwestern

BQ.1.1 is among the most immune-evasive COVID variants yet. Its coming in hot in the U.S. – Yahoo Finance

Posted on October 19, 2022 by Danzig

Omicron spawn BQ.1 and its offspringthe highly immune-evasive BQ.1.1are coming in hot in the U.S.

The duo comprises more than 11% of COVID cases, according to updated projections released Friday by the U.S. Centers for Disease Control and Prevention. The agency hadn't listed the variants until then because they were estimated to comprise less than 1% of those circulating. Previously, they had been reported under parent lineage BA.5.

Combined, the two are less than one percentage point away from taking the No. 2 spot in the nation, currently held by BA.4.6, estimated to comprise 12.2% of cases. Cases of leading variant BA.5 are on the decline, estimated to comprise less than 70% of cases as of Friday.

Important update of US genomic surveillance with noteworthy transition as BA.5 fades, BQ.1.1 quickly gains, along with other variants (BF.7, BA.2.75.2).https://t.co/jjl2AnwOWX pic.twitter.com/FuXdB42QuM

— Eric Topol (@EricTopol) October 14, 2022

"When you get variants like that, you look at what their rate of increase is as a relative proportion of the variants, and this has a pretty troublesome doubling time," Dr. Anthony Fauci, the nation's top infectious disease expert and the president's chief medical adviser, told CBS News on Friday.

BQ.1.1 is surging in New York, considered by experts to be a "bellwether" state due to its volume of incoming international travelers and robust sequencing capabilities. It's also rising in European countries like Germany, where Oktoberfest celebrations may have served as super-spreader events.

Along with XBBa combination of two Omicron strains spiking in Singapore and BangladeshBQ.1.1 is thought to be the most immune-evasive new variant, according to Dr. Eric Topol, a professor of molecular medicine at Scripps Research and founder and director of the Scripps Research Translational Institute.

BQ.1.1's extreme immune evasiveness "sets it up to be the principal driver of the next U.S. wave in the weeks ahead," Topol tweeted Friday.

On Thursday, he told Fortune that scientists won't know to what extent it challenge vaccines, if it does, until it reaches 30%-50% of cases somewhere.

Story continues

"It's not going to wipe out vaccine efficacy, but it could but a dent in protection against hospitalizations and death," he said.

BQ.1.1 is already known to escape antibody immunity, rendering useless monoclonal antibody treatments used in high-risk individuals with COVID. According to a study last month out of Peking Universitys Biomedical Pioneering Innovation Center in China, BQ.1.1 escapes immunity from Bebtelovimab, the last monoclonal antibody drug effective on all variants, as well as Evusheld, which works on some. Along with variants CA.1 and XBB, BQ.1.1 could lead to more severe symptoms, the authors wrote.

BQ.1.1 is one of two variants, including XBB, Topol says should be granted new Greek letter names, like Pi or Rho, because they differ enough from BA.5, the strain they derived from. He also said he would have assigned a Greek letter to BA.5, which was significantly distinct from ancestors BA.1 and BA.2.

The good news, if there is any, about BQ.1 and BQ.1.1 is that new Omicron boosters will "almost certainly" provide "some" protection against them because they were designed to tackle close relative BA.5, Fauci told CBS on Friday.

BQ.1 and BQ.1.1 were first detected in mid-July, according to a Oct. 5 risk assessment from the Ontario, Canada, public health department. It rates the risk level of increased transmissibility, reinfection, and reduced vaccination effectiveness against infection as high, with a high degree of uncertainty.

Some experts, including those at theInstitute for Health Metrics and Evaluationat the University of Washington, as well as Fauci, predict a coming wave of infections that will swell this month and peak in late December or early January.

As of Thursday, the seven-day average of cases reported to the CDC sat just under 38,000 a day. With testing at all-time lows, it's widely accepted that case numbers reported to the agency, and thus reported by it, pale in comparison to the actual number of cases in the U.S.

This story was originally featured on Fortune.com

Without a nasal vaccine, the U.S. edge in fighting Covid is on the line – POLITICO

Posted on October 19, 2022 by Danzig

India, Russia and Iran have authorized nasal vaccines. And while none of those have yet been proven to stop Covid transmission, officials say the U.S. could find itself at a global disadvantage, particularly if a deadlier variant emerges.

Intranasal vaccines vaccines that are variant-resistant those are critical tools to have in the toolbox for protecting Americans, not just for Covid but also for future pandemics and also for future biosecurity threats, Ashish Jha, the administrations Covid-19 response coordinator, told POLITICO.

Researchers working on nasal vaccines are hopeful that they could stop virus transmission by generating immunity against it in the nose and other parts of the upper respiratory system where the coronavirus enters the body. If that bears out in clinical trials, nasal vaccines would be superior to existing mRNA vaccines, which prevent severe disease but dont stop transmission.

Officials at the National Institute of Allergy and Infectious Diseases are attuned to the danger of failing to develop such a nasal vaccine since it would protect people in case of a more contagious and deadlier coronavirus variant, said Karin Bok, the acting deputy director for pandemic preparedness and emergency response at the agencys Vaccine Research Center.

The center has mapped the nasal and oral Covid vaccines in development in the U.S. and abroad. It is also testing nasal versions of the Moderna vaccine and two other types of injectable Covid-19 vaccines in monkeys, Bok said. But that probably wont lead to a nasal Covid vaccine being approved in the U.S. anytime soon because funding for clinical trials and production is lacking.

Bok and Jha say the cost is high. If China were to develop a nasal vaccine capable of stopping Covid transmission, that could turn the tables on the current pandemic trajectory, which has the U.S. emerging and much of China stuck in lockdown.

Even though India, Iran, China and Russia havent proved their non-injectable vaccines stop transmission, the potential is there, experts said.

Countries where transmission is reduced are going to be healthier, are going to have stronger economies. And the U.S. needs to catch up, said Marty Moore, the founder and chief scientific officer of Meissa Vaccines, a small biotech company thats trying to develop a nasal vaccine in the U.S.

Many scientists believe the nose could hold the secret to stopping coronavirus transmission, but theres no consensus yet on whether nasal vaccines could be more effective than injectable ones, as evidence from clinical trials is necessary to prove it.

Disagreement in Congress about how to pay for additional aid or whether its needed, as well as disinterest from major drugmakers in spending their own money on something that may not be very profitable, could mean a foreign rival gets an advantage.

Writing in Science Immunology in July, Eric Topol, a professor of molecular medicine at Scripps Research, and Akiko Iwasaki, an immunobiology professor at Yale, endorsed the potential of a nasal vaccine to stop coronavirus transmission. Breaking the chain of transmission at the individual and population level will put us in a far better position to achieve containment of the virus, they wrote, adding that the prospect of achieving this with nasal vaccines is high.

They called for U.S. government support in developing Operation Warp Speed 2.0, modeled on the initiative that created the first Covid-19 vaccines in record time. The Biden administration is working on that, but funding woes and pandemic fatigue have hampered its efforts.

Beyond effectiveness, a nasal vaccine could appeal to people who are squeamish about needles and to parents of young children who have mostly declined to get their kids inoculated. As of early October, only 9 percent of children ages 6 months to 5 years have gotten the shots, which were authorized by the FDA in June.

Outside of the government-funded research cited by Bok, two Washington University School of Medicine professors, David T. Curiel, a radiation oncologist, and Michael S. Diamond, a molecular microbiologist, invented the nasal vaccine authorized in India.

Curiel and Diamond told POLITICO they created it with the needs of the developing world in mind, given the lack of ultracold freezers needed to store mRNA vaccines. The two scientists licensed their vaccine to the Indian drugmaker Bharat Biotech, which tested it in clinical trials partially financed by the Indian government. They have also tried to solicit interest from large U.S. pharmaceutical companies about it and there was not as much excitement as we would have thought, Diamond said.

Their vaccine, named iNCOVACC in India, is based on an adenovirus that delivers the coronavirus spike protein.

Bharat Biotech tested it both as a primary vaccination series and as a booster for people who were vaccinated with injectable Covid shots available in India. The company said the clinical trials had successful results and that side effects were comparable to those from other Covid-19 vaccines, but it has not yet published the data in a peer-reviewed scientific journal.

The Indian drug regulator approved the two-dose vaccine, which comes in the form of nasal drops, for adults who have not had a previous Covid-19 shot, Bharat Biotech said. The company has the right to sell it in India and most of the rest of Asia and Africa.

Elsewhere, the Coalition for Epidemic Preparedness Innovations, a global partnership financing vaccine development for epidemic threats, is developing a plan for nasal vaccine research projects.

For example, we are looking into whether nasal vaccines could be an option for our all-in-one coronavirus vaccine program funding the development of vaccines against both Covid-19 variants and other coronaviruses, said Melanie Saville, CEPIs executive director of vaccine research and development.

CEPI awarded nearly $5 million in seed funding to the Dutch company Intravacc for a nasal vaccine candidate that could work against multiple coronaviruses.

There are now 95 nasal vaccines under development around the world, according to health data company Airfinity. Six have reached the final Phase 3 in clinical trials.

But some scientists doubt that a nasal vaccine will be a game-changer.

William Haseltine, a former professor at Harvard Medical School with expertise in HIV/AIDS and genomics, believes that enthusiasm should be tempered about the potential of nasal vaccines to prevent infection, given that natural nasal exposure to the virus doesnt prevent people from getting reinfected.

Why in the world do you think that if you [spray] a vaccine up the nose you can do any better? he asked POLITICO.

Attempts to develop a nasal version of the AstraZeneca Covid-19 vaccine, the injectable version of which was widely used globally at the beginning of the vaccination campaign, experienced a setback after only a minority of participants in an early stage clinical trial showed some immune response in respiratory mucous membranes.

Haseltine argued that scientists still dont have a good understanding of nasal immunity and that government funding would be better directed to antiviral drugs that keep Covid-19 in check.

And Bok doesnt think any of the existing non-injectable vaccines stop Covid-19 transmission. I would be very surprised if India or China licensed it with data proving that an intranasal vaccine is better than the ones we have, she said.

Curiel and Diamond have licensed their vaccine for potential use in the U.S. to Pennsylvania-based biotech Ocugen.

The company is looking for both regulatory and financial support from the U.S. government to develop the vaccine as a booster, CEO Shankar Musunuri told POLITICO.

But without another Operation Warp Speed, there will be substantial delays in large-scale manufacturing, regulatory approval and distribution of a nasal vaccine, argued Topol and Iwasaki.

Iwasaki, who is working to develop a booster Covid-19 nasal vaccine, said she will probably need tens of millions of dollars to test it in clinical trials. Just trying to do this as a small academic lab is very different from a Warp Speed, she told POLITICO.

Thats unlikely to happen.

Congress last month passed a short-term measure to continue funding the government until Dec. 16 without any additional money for Covid-19. The White House had asked for $8 billion to fund the next generation of vaccines and therapeutics, including nasal vaccines.

There is no plan B: If Congress does not fund this, it will not happen, Jha said. America will fall further behind China and other countries.

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Without a nasal vaccine, the U.S. edge in fighting Covid is on the line - POLITICO

American Molecular Labs selects 1health.io for its Direct-to-Consumer Test and Ordering Platform – Business Wire

Posted on October 19, 2022 by Danzig

SAN FRANCISCO--(BUSINESS WIRE)--American Molecular Laboratories (AML), a state-of-the-art molecular diagnostic and biotech development company based in Chicago, Illinois, selects 1health.io, an industry-leading software company revolutionizing the way laboratories expand testing into the at-home markets, to deliver its innovative new lab tests direct-to-consumers.

American Molecular Laboratories specializes in the diagnosis of infection, disease, and early detection cancer screening predominantly in the gastrointestinal tract. The Company is most notable for its proprietary Helicobacter pylori (H. pylori) bacterial test.

H. pylori is one of the most common chronic bacterial infections found in humans, affecting approximately 4.4 billion individuals worldwide (Hooi et al., 2017, Global Prevalence of Helicobacter pylori Infection: Systematic Review and Meta-Analysis. Gastroenterology), and it is considered a major contributor to the pathogenesis of peptic ulcer disease and other gastric malignancies including cancer and mucosa-associated lymphoid. H. pylori infection is one of the leading causes of Antibiotic resistance in the world and AMLs PyloriDx is the new gold standard to facilitate the most effective antibiotic treatment for H pylori.

The new partnership between 1health and American Molecular Laboratories will enable AML to establish a market presence, selling its food sensitivity, food allergy, and other patent-pending tests, into the direct-to-consumer lab testing market which is forecast to grow at a 22.6% compound annual growth rate over the next ten years, hitting $8.8 billion by 2031 according to research group, Transparency Marketing in its report North America Direct-to-Consumer Laboratory Testing Market Insights, 2021-2031 published in Q1 2022.

We have a strong science team that is driving innovation, accuracy, and efficiency within American Molecular Labs. Because of this unique differentiator, we can offer products that are reliable, easy to collect, and affordable, states President & Founder, Sam Zhang. Now, with the 1health platform, we have a solution that enables us to offer some of our most popular tests, at competitive price points, directly to consumers, clinicians, and even other lab partners. We are able to deploy these tests quickly and end-to-end which gives us another competitive advantage in the marketplace, Zhang adds.

1health offers clinical and direct-to-consumer solutions that connect into its platform enabling labs to sell tests to their customers via an intuitive user portal. The lab can then manage patient information securely, including kit registration, sample tracking, notifications, and reporting, among a host of other features.

American Molecular Laboratories offers the only test in the world, its H. pylori test, that uses a non-evasive mechanism to test gastric malignancies, including certain types of cancer and lymphomas. This test can help save thousands of lives, states 1health CEO Mehdi Maghsoodnia. Now, with our platform, AML can now take this highly-specialized test and its other innovative health and wellness tests to many channels, including selling to physicians, labs, and consumers, Maghsoodnia continues.

We are proud they have selected the 1health platform to meet their needs in both the clinical and direct-to-consumer markets, added Maghsoodnia.

About American Molecular Laboratories

American Molecular Laboratories (AML) is a state-of-the-art molecular diagnostic and biotech development company that was founded by Sam Zhang and an expert scientific team in molecular diagnostics.

Located in Chicagos north suburbs, AML utilizes molecular analytic tools and methodologies to design, develop, and implement cutting-edge diagnostic medicine solutions. Its research and product development programs are focused on the diagnosis of infection, disease, and early detection cancer screening predominantly in the gastrointestinal tract.

AML provides testing services and products to hospitals, clinics, and labs. The Company also serves major pharmaceutical companies by providing molecular testing solutions in drug development and research. Learn more at http://www.amlaboratories.com.

About 1health.io

1health is driving healthcare innovation by revolutionizing the way laboratories service medical providers and consumers. By providing a modern, secure, and easy-to-use software platform, 1health enables diagnostic testing results to be accurately delivered in minutes, not days or weeks, thereby reducing costs and expanding growth opportunities for laboratories. The result is stronger, more-trusted relationships between laboratories and their customers, better healthcare outcomes for consumers, and ultimately more lives saved.

1health is proud to help leading-edge laboratories like St. Jude Labs, Thomas Scientific, Apollo Laboratories, Premier Lab Solutions, Gene by Gene, and many others and provides testing services to hundreds of leading enterprise companies including Raleys, Starbucks, Cruise, and the U.S. Air Force. Learn more at: http://www.1health.io.

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American Molecular Labs selects 1health.io for its Direct-to-Consumer Test and Ordering Platform - Business Wire

Kyverna Therapeutics Submits IND for Novel CAR T-Cell Therapy to Treat Lupus Nephritis – PR Newswire

Posted on October 19, 2022 by Danzig

- Company files its first Investigational New Drug application for its lead program KYV-101, a novel fully human CD19 CAR T-cell therapy, for the treatment of lupus nephritis

- Kyverna's therapeutic platformcombines advanced T-cell engineering and synthetic biology technologies to suppress and eliminate autoreactive immune cells at the root cause of inflammatory disease

EMERYVILLE, Calif., Oct. 18, 2022 /PRNewswire/ -- Kyverna Therapeutics ("Kyverna"), a cell therapy company with the mission of engineering a new class of therapies for serious autoimmune diseases, today announced the filing of its first Investigational New Drug (IND) application to the U.S. Food and Drug Administration (FDA) for KYV-101, a novel therapy for the treatment of lupus nephritis.

Lupus nephritis (LN) is a serious complication of systemic lupus erythematosus (SLE), more commonly known as lupus. Approximately 40 percent of adults diagnosed with lupus eventually develop LN and 60 percent of LN patients will fail standard of care and approved treatments1. Aside from modest efficacy, current treatments expose these young adults to the well-demonstrated detrimental consequences of chronic treatment with corticosteroids and other powerful immunosuppressants. Up to 10 percent of patients with LN and 40 percent with diffuse LN (class IV) will ultimately develop kidney failure, requiring dialysis or a kidney transplant to stay alive2.

KYV-101 is an autologous version of a novel, fully human clinical-stage anti-CD19 chimeric antigen receptor T-cell (CAR T) construct with properties well suited for use in B cell-driven autoimmune diseases such as lupus nephritis and other B-cell driven autoimmune diseases. In a 20-patient Phase 1/2 study in oncology, expected anti-lymphoma activity was associated with a significant reduction of cytokines releasedthat translated into a strong reduction of cytokine-driven side effects such as the rate of immune effector cells-associated neurotoxicity syndrome (ICANS)3. The fully human anti-CD19 CAR also translated into reduced immunogenicity that favorably impacted cell persistence at one month. Kyverna recognized that these properties singled out KYV-101 as a product ideally poised for use in autoimmune disease patients, and the company obtained exclusive, worldwide licenses from the National Institutes of Health (NIH) to use this CD19 construct in both autologous and allogeneic CAR T-cell therapies. Pending results of the FDA review, Kyverna is actively working with clinical sites in the U.S. and Europe to support initiation of the Phase 1/2 study in LN.

"We are extremely proud to be leading a possible revolution in how we treat severe immune-related and inflammatory diseases. The filing of this IND for KYV-101 in lupus nephritis is an important milestone for Kyverna and we are excited by the prospect of KYV-101 opening a new era in the care of patients with LN. We strongly believe that KYV-101 may drastically change the course of this devastating disease," said Peter Maag, Ph.D., chief executive officer of Kyverna Therapeutics. "We look forward to working with the FDA to initiate the KYV-101 clinical study."

"Patients with lupus nephritis too often experience serious complications from the medications used to control the disease process or from the disease itself. We applaud the team at Kyverna for developing novel treatment approaches for these patients that today have very limited treatment options," said Richard A. Furie, M.D., The Marilyn and Barry Rubenstein Chair in Rheumatology, professor, Institute of Molecular Medicine, Feinstein Institutes for Medical Research, chief of Division of Rheumatology, Northwell Health, and professor of medicine, Donald and Barbara Zucker School of Medicine at Hofstra University/Northwell Health.

About KYV-101KYV-101 is an autologous version of a novel fully human clinical-stage anti-CD19 chimeric antigen receptor T-cell (CAR T) construct with properties well suited for use in B cell-driven autoimmune diseases such as lupus nephritis, systemic sclerosis, and inflammatory myopathies. Kyverna has obtained exclusive, worldwide licenses from the National Institutes of Health (NIH) to use this CD19 construct in both autologous and allogeneic CAR T-cell therapies.

About Kyverna TherapeuticsKyverna Therapeutics is a cell therapy company with the mission of engineering a new class of therapies for autoimmune and inflammatory diseases. The Kyverna therapeutic platform combines advanced T-cell engineering and synthetic biology technologies to suppress and eliminate the autoreactive immune cells at the origin of autoimmune and inflammatory diseases. In addition to aiming to develop next-generationchimeric antigen receptor T-cell (CAR T) therapies in both autologous and allogeneic settings, Kyverna is creating synReg T cells, a synthetic version of Regulatory T cells (Tregs), powerful natural immune cells that control immune homeostasis through multiple immunosuppressive mechanisms. By offering more than one mechanism for taming autoimmunity, Kyverna is positioned to act on its mission of transforming how autoimmune diseases are treated. For more information, please visithttps://kyvernatx.com.

1 E. Carter et al., Nature Reviews Rheumatology, 12, Oct. 2016, 605-620.2 Adv Chronic Kidney Dis. 2019;26(5):313.3 Brudno et al., Nature Medicine 2020; 26:270-280.

SOURCE Kyverna Therapeutics

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COVID-19: Multiple variants dominate the world. What will happen next? – WION

Posted on October 19, 2022 by Danzig

The health department of India's southern state Maharashtra has raised an alert over coronavirus (COVID-19) cases that may increase after the detection of new variants like BA.2.3.20 and BQ.1 reported from the state. For the first time, the variants have been detected in the country.

Health officials in the country are also concerned and have cautioned people as cases are expected to rise especially during the winter and the festive season.

The Maharashtra health department noted that the new XBB variant of coronavirus has a growth advantage over BA.2.75 and has immune evasive properties.

The bulletin said: "Some experts are predicting a rise in the coming winter season, especially in the festive environment. In WGS (whole genome sequencing), the proportion of BA.2.75 has decreased to 76 per cent from 95 per cent."

The variants are fueling cases globally. In some countries, including the United Kingdom, Germany and the United States, some are emerging as a strain responsible for maximum cases, especially BQ.1.

The US Centers for Disease Control and Prevention (CDC) noted that the BQ.1 and BQ.1.1 infections were currently 11 per cent of the country's caseloadacross the nation in the week ending October15.Less than a month ago, the pair were in just 1 per cent of cases. The steep rise is concerning the experts.

Watch this report:

Covid and its variants

When it comes to coronavirus variants, people have probably given up on keeping track of all the variants that are emerging now and then mostly the offspring of the Omicron variant. Notably, the variants are different in different parts of the world right now.

News outlet Fortune reported that the way Omicron variants are quickly growing globally is "unprecedented". The other feature concerning traits as some have improved immune evasion, increased transmissibility, or in some cases both.

As per the experts, the coronavirus could end up something like mild flu, or it might become bigger than what it is right now.

Dr Eric Topol, who is a professor of molecular medicine at Scripps Research and founder and director of the Scripps Research Translational Institute, told Fortune: "There have been times when different variants were on the move in different parts of the world, like the Gamma variant in South America, and Beta in South Africa."

"But this is different because now we have variants with extreme levels of immune evasion, and in any given country, potentially a few that could be in play at the same time," Dr Topol added.

Will it end up like flu?

It is vital that appropriate analysis is done timely to learn about the spread of variants as the fragmented cluster of Covid variants has been scattered around the globe.

Dr Ali Mokdad, a professor at the University of Washington's Institute for Health Metrics and Evaluation, told Fortune: "Many people globally are becoming susceptible all over again due to waning immunity from the vaccine and infections. People who have gotten Omicron BA.5 are susceptible five, six months later. Therefore anything circulating out there, theyre going to catch it."

According to Mokdad, the Covid virus will eventually become like the flu, which spear most during the winter season. In some years, the impact of the virus is worse than in others. He said that such a phenomenon with Covid could make it possible to target the virus with a single annual shot.

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COVID-19: Multiple variants dominate the world. What will happen next? - WION

Researchers uncover how breast cancer cells become resistant to therapy – EurekAlert

Posted on October 19, 2022 by Danzig

About one-fourth of recurrent estrogen receptor-positive (ER+) breast cancers lose ER expression, which renders them resistant to endocrine therapy and able to grow uncontrolled. A team of researchers at Baylor College of Medicine has investigated how these cells lose their ER, and in the current study published in theProceedings of the National Academy of Sciences, they reveal a mechanism that not only explains the process but also offers possibilities to overcome it.

For years, our goal has been to tease out the complex puzzle of breast cancer progression to understand how the players interact with each other to confer resistance to therapy and persistent growth, said corresponding author Dr. Weei-Chin Lin, professor of medicine hematology and oncology and of molecular and cellular biology at Baylor. Our goal is to overcome this hurdle to restore ER receptor expression in these cancers so they become susceptible to therapy again, giving patients a better chance for recovery.

How breast cancer cells lose their ER

Two cellular proteins known as 14-3-3 and ER36 have been previously implicated in the development of breast cancer resistance to endocrine therapy.

Working with a mouse model of human ER+ breast cancer, we were surprised to find that over-expressing 14-3-3 in these tumors led to all the cancer cells becoming ER-negative (ER-), said Lin, a member of the Dan L Duncan Comprehensive Cancer Center. I still remember the day I saw the data. The change was dramatic all the tumors had lost their ER!

Studying the mechanism in animal models would be labor intensive, time consuming and expensive, so the researchers developed an alternative model. First author Lidija A. Wilhelms Garan, a student in Baylors Cancer and Cell Biology Graduate Program working in the Lin lab, developed a spheroid model of human breast cancer cells that mimics the progression from ER+ to ER- and provides a very useful experimental tool for future investigation.

In a patient, a breast tumor can take years to progress from ER+ to ER-, in our animal model it takes several months but in our spheroid model it switches from ER+ to ER- in 1 to 2 weeks, Garan said.

In the lab spheroid model the team found that once 14-3-3 is over-expressed in cancer cells under the right conditions, the cells will increase their levels of ER36 and this is followed by ER loss.

Other molecular players, such as AKT and GATA3, also are required, Garan said. Importantly, we also found that factors produced by the tumor microenvironment, which includes fibroblasts and immune cells that are part of the tumor mass and cross talk with the cancer cells, also are essential for the progression from ER+ to ER-.

We knew that 14-3-3, ER36, AKT and GATA3 were the key players involved in turning ER+ breast cancer cells into ER- cells. Here we have determined how they functionally interact with each other, laying out a map of the road that leads to ER loss, Lin said. I am very excited that with our spheroid breast cancer model we now have a valuable tool to study not only the cellular changes involved in breast cancer progression but also to test drugs for their ability to inhibit the process that leads to ER loss.

The protein 14-3-3 is overexpressed in about 60% of breast cancers. Not all patients that have high 14-3-3 will lose the ER, but for those who do, our findings may one day help restore their tumors to a therapy-sensitive state, Garan said. The translational aspect of this research has always been close to my heart to bring discoveries to the clinic and improve peoples lives.

Yang Xiao at Baylor College of Medicine also was an author of this work.

This work was supported by NIH Grants R01CA203824, R01CA100857, R21CA198041, T32GM136560 and T32CA174647 and Department of Defense Grants W81XWH-18-1-0329 and W81XWH-19-1-0369.

About one-fourth of recurrent estrogen receptor-positive (ER+) breast cancers lose ER expression, which renders them resistant to endocrine therapy and able to grow uncontrolled. A team of researchers at Baylor College of Medicine has investigated how these cells lose their ER, and in the current study published in the Proceedings of the National Academy of Sciences, they reveal a mechanism that not only explains the process but also offers possibilities to overcome it.

How breast cancer cells lose their ER

Two cellular proteins known as 14-3-3 and ER36 have been previously implicated in the development of breast cancer resistance to endocrine therapy.

In a patient, a breast tumor can take years to progress from ER+ to ER-, in our animal model it takes several months but in our spheroid model it switches from ER+ to ER- in 1 to 2 weeks, Garan said.

In the lab spheroid model the team found that once 14-3-3 is over-expressed in cancer cells under the right conditions, the cells will increase their levels of ER36 and this is followed by ER loss.

Yang Xiao at Baylor College of Medicine also was an author of this work.

This work was supported by NIH Grants R01CA203824, R01CA100857, R21CA198041, T32GM136560 and T32CA174647 and Department of Defense Grants W81XWH-18-1-0329 and W81XWH-19-1-0369.

Proceedings of the National Academy of Sciences

Experimental study

Human tissue samples

14-3-3 drives estrogen receptor loss via ER36 induction and GATA3 inhibition in breast cancer

17-Oct-2022

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Researchers uncover how breast cancer cells become resistant to therapy - EurekAlert

The magic of active matter – EurekAlert

Posted on October 19, 2022 by Danzig

Biology solves a myriad of seemingly impossible physical challenges through the magic of active matter. Consider our lungs, for example. Using active-matter surfaces, they clear an astronomically large number of particulate contaminants that accompany each of the ten thousand liters of air we respire every day, ensuring that the lungs gas exchange surfaces remain functional.

Scientists and engineers are interested in active matter because it operates out of thermodynamic equilibrium, taking energy from its environment and using it to move or do work. That includesSho Takatori, an assistant professor of chemical engineering at UC Santa Barbara, who with his research group is working to achieve a deeper understanding of active matter, studying how it generates internal forces to control physical and chemical processes. That fundamental knowledge of the dynamics and unique properties of active matter may enable the design of synthetic materials with tunable properties, like the gas exchange and self-cleaning surfaces in our lungs.

Most engineered surfaces are designed to perform only a single task, like gas exchange or chemical catalysis. And they often have a chronic problem of surface contamination that clogs and deactivates the surface, explained Takatori. My lab envisions the development of multifunctional surfaces that enable the simultaneous operation of molecular sensing, recognition and catalysis. Active matter will play a central role in our mission.

In support of his leading-edge study of active matter, Takatori has received a prestigious Packard Fellowship for Science and Engineering from theDavid and Lucile Packard Foundation.

I am extremely honored and grateful to join this prestigious group of scientists and engineers as a Packard Fellow, said Takatori, who earned his Ph.D. in chemical engineering from the California Institute of Technology. Many scientists and engineers who I have respected and admired since I was a Ph.D. student have been Packard Fellows. Their accomplishments have inspired me to dream, which is why this fellowship is especially meaningful to me. The funding will also allow my lab to take creative approaches to high-risk, high-reward projects.

Takatori is one of only twenty early-career scientists and engineers from across the country who were named tothis years class of Packard Fellows, who each receives $875,000 over five years to take creative approaches to their research, dare to think big and follow new ideas wherever they lead. Since its creation in 1988, the Packard Foundation has awarded nearly $500 million to support more than 680 scientists and engineers. Packard Fellows have gone on to receive major awards and recognitions, including Nobel Prizes, Fields Medals and elections to the National Academies of Engineering, of Sciences, and of Medicine.

The College of Engineering is tremendously proud of Professor Takatori for receiving a Packard Fellowship, the largest non-governmental fellowship and one of the most prestigious early-career awards, saidTresa Pollock,the interim dean of the College of Engineering and Alcoa Distinguished Professor of Materials. He has already established himself as a leader in the fields of active matter and cell membrane engineering, and this recognition allows him to push the boundaries of discovery even further to improve our quality of life.

In his project, Takatori seeks to use basic active-matter components mechanical motor, driven constituent and energy source to engineer synthetic surfaces that actuate multifunctional properties.

Our goal is to direct the flow of matter by orchestrating these living molecules found within biological systems, guided by new fluid mechanics models and advanced computations, said Takatori.

In order to transform their vision into reality, his group must overcome key obstacles in the fields of fluid mechanics and surface science, which is the study of the physical and chemical phenomena that occur at the interface of two phases. A major goal is generating surface flows in the absence of any externally imposed force, a grand challenge in fluid mechanics. In most systems, like water flowing through a pipe, an externally imposed pressure drop is required to create flow and movement in the system. Takatori wants to createinternalforces to actuate surface flows by directing active matter, which can be used to control the transport of molecules on surfaces. Possible applications for such a technology include sensors that can detect the presence of molecular species in the fluid, surfaces that instinctively self-assemble in a specific geometry and catalytic surfaces that increase the rate of chemical reactions in the system.

Our new theoretical framework is the key enabling breakthrough that will allow us to predict and design nonequilibrium active matter, said Takatori. This is significant because existing textbook theories often fail to predict the behavior of materials driven out of equilibrium, like batteries, biological tissues and other systems that dynamically change with time and/or space. Active matter serves as a good model system to advance new theories that may be applied to a variety of chemical and physical systems.

Takatori said that his research group possesses the ability to complete this project by combining theory, simulation and experiments to control and design active-matter surfaces with desired properties.

The successful realization of this technology would generate tunable, living surfaces that combine the dynamic programmability of active matter and the molecular specificity of biological membranes, he said. Our hope is that this project will lead to the design of multifunctional surfaces that can perform sensing and communication in ways that have never been achieved.

Takatori is the fourth Packard Fellow among the chemical engineering departments eighteen faculty members an indication, he said, of the high-quality research and teaching that takes place within the department and across the university.

Packard Fellows are dared to think big, explore new frontiers and follow uncharted paths that may lead to groundbreaking discoveries, said Takatori. The fact that more than 20% of our faculty are recipients is one of the many testaments to the creative science and engineering that the faculty direct. It also displays the strength and innovativeness of our departments exceptionally talented students and postdoctoral researchers who take off with exciting, out-of-the-box ideas.

We are thrilled that the David and Lucile Packard Foundation recognizes and supports the high-impact potential of Professor Takatoris research, saidRachel Segalman,chair of chemical engineering. This award affords him the opportunity to take risks in pursuit of scientific breakthroughs that would improve peoples lives and revolutionize everything from medicine to robotics.

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Replay establishes distinguished Scientific Advisory Board of genomic medicine and cell therapy experts – GlobeNewswire

Posted on October 19, 2022 by Danzig

Replay establishes distinguished Scientific Advisory Board of genomic medicine and cell therapy experts

San Diego, California and London, UK, October 17, 2022 Replay, a genome writing company reprogramming biology by writing and delivering big DNA, today announced that it has established a scientific advisory board (SAB) comprising ten experts across a broad range of areas of scientific importance in genomic medicine and cell therapy.

The newly formed SAB will provide input into Replays strategy, portfolio of next-generation genomic and cell therapy medicines, and associated technology platforms. The SAB complements Replays industry seasoned management team and board.

Adrian Woolfson, Executive Chairman, President and Co-founder of Replay, commented: The multi-disciplinary nature of our scientific advisory board reflects Replays commitment to invoking innovation from a broad range of scientific specialties and leveraging this across our research and development programs. Our new advisors represent some of the best scientific minds of their generation and bring a unique and differentiated portfolio of expertise into the Company. Their contribution to Replay will be invaluable as we continue to address some of the most significant challenges in genomic medicine and cell therapy.

Lachlan MacKinnon, Chief Executive Officer and Co-founder of Replay, added: Following on from our recent launch, the formation of our uniquely distinguished scientific advisory board further demonstrates Replays commitment to developing a cutting-edge portfolio of medicines guided by world-class science. The combined inter-disciplinary expertise of our scientific advisory board brings tremendous knowledge and experience into the Company as we continue to expand our operations, with a view to developing transformative genomic medicines.

Replays SAB will be chaired by Professor Roger Kornberg, PhD, a biochemist whose laboratory work has focused on the molecular basis of eukaryotic transcription and in particular the structure of RNA polymerase and the nucleosome.

Professor Roger Kornberg, PhD, Chairman of Replays Scientific Advisory Board, said: Replays scientific advisory board incorporates expertise across several areas relevant to Replays genomic medicine and cell therapy technology platforms. I am excited to be working with this exceptional group of scientists and believe we can make a compelling contribution and help Replay realize its vision for genomic medicine.

Replays SAB members are as follows:

Professor Roger D. Kornberg PhD (Chairman), is the Winzer Professor of Medicine in the Department of Structural Biology at Stanford University School of Medicine. He was awarded the Nobel Prize in Chemistry (2006).

Professor Carl H. June, MD, is the Richard W. Vague Professor in Immunotherapy in the Department of Pathology and Laboratory Medicine at the Perelman School of Medicine at the University of Pennsylvania. He is Director of the Parker Institute for Cancer Immunotherapy at the University of Pennsylvania, Director of the Center for Cellular Immunotherapies at the Perelman School of Medicine, and Director of Translational Research at the Abramson Cancer Center. He was the co-founder of TMunity.

Professor Robert S. Langer, ScD, FREng,is one of 12 Institute Professors at the Massachusetts Institute of Technology (MIT), co-founder of Moderna, and was formerly Chair of the FDAs Science Board. He has been awarded 40 honorary doctorates, written over 1,500 articles, and received over 220 awards.

Professor Lynne E. Maquat, PhD, is the J. Lowell Orbinson Endowed Chair and Professor of Biochemistry and Biophysics, University of Rochester Medical Center, and founding Director of the Center for RNA Biology, University of Rochester, Rochester NY. She was awarded the Wolf Prize in Medicine from Israel (2021) and the Warren Alpert Foundation Prize from Harvard Medical School (2021).

Professor Dame Carol Robinson, DBE FRS FMedSci FRSC, is the Dr Lees Professor of Physical and Theoretical Chemistry, the Founding Director of the Kavli Institute for Nanoscience Discovery at Oxford, and a Founder of OMass Therapeutics. She is a Professorial Fellow at Exeter College, Oxford, and was formerly President of the Royal Society of Chemistry.

Professor David V. Schaffer, PhD, is the Hubbard Howe Professor of Chemical and Biomolecular Engineering, Bioengineering, and Neuroscience at the University of California, Berkeley, where he is Director of theBakar BioEnginuity Hub and Director of the California Institute for Quantitative Biosciences (QB3). He was the co-founder of 4D Molecular Therapeutics, Ignite Immunotherapies, Rewrite, and 5 additional companies.

Professor Stuart L. Schreiber, PhD, is the Morris Loeb Professor of Chemistry and Chemical Biology at Harvard University. He is a co-founder of the Broad Institute at Harvard University and MIT and co-founder of Harvards Institute of Chemistry and Cell Biology. He was awarded the Wolf Prize in Chemistry (2016).

Professor Pamela Silver, PhD, is the Elliot T. and Onie H. Adams Professor of Biochemistry and Systems Biology in the Department of Systems Biology at Harvard Medical School, and a founding member of the Wyss Institute for Biologically Inspired Engineering at Harvard Medical School.

Professor Sir John E. Walker, FRS FMedSci, is Emeritus Director and Professor at the MRC Mitochondrial Biology Unit at the University of Cambridge, England, and a fellow of Sidney Sussex College, Cambridge. He was awarded the Nobel Prize in Chemistry (1997).

Professor John Fraser Wright, PhD, is Professor of Pediatrics, Division of Hematology, Oncology, Stem Cell Transplantation and Regenerative Medicine, and Director of Technology Innovation at the Center for Definitive and Curative Medicine at Stanford University. He is co-founder and was Chief Technology Officer at Spark Therapeutics and is co-founder and Chief Scientific Advisor at Kriya Therapeutics.

Ends

About Replay

Replay is a genome writing company, which aims to define the future of genomic medicine through reprogramming biology by writing and delivering big DNA. The Company has assembled a toolkit of disruptive platform technologies including a high payload capacity HSV platform, a hypoimmunogenic cell therapy platform, and a genome writing platform to address the scientific challenges currently limiting clinical progress and preventing genomic medicine from realizing its full potential. The Companys hub-and-spoke business model separates technology development within Replay from therapeutic development in product companies that leverage its technology platforms. For example, Replays synHSV technology, a high payload capacity HSV vector capable of delivering up to 30 times the payload of AAV, is utilized by Replays four gene therapy product companies, bringing big DNA treatments to diseases affecting the skin, eye, brain, and muscle. The Company has, additionally, established an enzyme writing product company that leverages its evolutionary inference machine learning and genome writing technology to optimize enzyme functionality. Replay is led by a world-class team of academics, entrepreneurs, and industry experts.

The Company raised $55 million in seed financing in July 2022 and is supported by an international syndicate of investors including: KKR, OMX Ventures, ARTIS Ventures, and Lansdowne Partners.

Replay is headquartered in San Diego, California, and London, UK. For further information please visit http://www.replay.bio and follow us on LinkedIn and Twitter.

Contacts:

Replay

Dr Adrian Woolfson/Lachlan MacKinnon

info@replay.bio

Consilium Strategic Communications Media relations

Amber Fennell/Tracy Cheung/Andrew Stern

replay@consilium-comms.com

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Replay establishes distinguished Scientific Advisory Board of genomic medicine and cell therapy experts - GlobeNewswire

In Depth | Deep Impact (EPOXI) NASA Solar System Exploration

Posted on October 19, 2022 by Danzig

What was Deep Impact (EPOXI)?

The primary mission of NASA's Deep Impact was to probe beneath the surface of a comet. The spacecraft delivered a special impactor into the path of Tempel 1 to reveal never-before-seen materials and provide clues about the internal composition and structure of a comet.

Impactor:1. Impact or Targeting Sensor (ITS)

Jan. 12, 2005: Launch

July 1, 2005: Comet P/Tempel 1 rendezvous

July 4, 2005: Comet impact

Aug. 2005: End of the primary mission

Nov. 4, 2010: Flyby of 103P/Hartley 2 comet

Aug. 11-Aug. 14, 2013: Communications lost

Sept. 20, 2013: NASA ends efforts to contact spacecraft

Unlike previous cometary flyby missions, such as Vega, Giotto, and Stardust, the Deep Impact spacecraft, the eighth mission in NASAs Discovery program, was intended to study the interior composition of a comet by deploying an impact probe that would collide with its target.

The spacecraft was comprised of two parts: the main flyby spacecraft and an impactor. The flyby spacecraft weighed 1,325 pounds (601 kilograms), was solar-powered, and carried two primary instruments.

The high-resolution instrument (HRI), the main science camera for Deep Impact, was one of the largest space-based instruments ever built for planetary science. It combined a visible-light multi-spectral CCD camera (with a filter wheel) and an imaging infrared spectrometer called the spectral imaging module (SIM). The medium-resolution instrument (MRI) was the functional backup for the HRI, and like the HRI, it served as a navigation aid for Deep Impact.

The impactor weighed 820 pounds (372 kilograms) and carried the impactor targeting sensor (ITS), nearly identical to the MRI, but without the filter wheel, which was designed to measure the impactors trajectory and to image the comet from close range before impact.

One of the more unusual payloads onboard was a compact disc with the names of 625,000 people collected as part of a campaign to Send Your Name to a Comet!

After launch, Deep Impact was put into low Earth orbit, then an elliptical orbit (about 100 x 2,600 miles or 163 4,170 kilometers), and after a third stage burn, the spacecraft and its PAM-D upper stage departed on an Earth escape trajectory.

There were some initial moments of anxiety when it was discovered that the spacecraft had automatically entered safe mode shortly after entering heliocentric orbit. By Jan. 13, 2005, Deep Impact had returned to full operational mode following a program to tumble the vehicle using its thrusters.

The spacecraft traveled 267 million miles (429 million kilometers) in six months (including course corrections on Feb. 11 and May 4, 2005) to reach Comet 9P/Tempel.

As the spacecraft approached its target, it spotted two outbursts of activity from the comet on June 14 and June 22, 2005.

On July 3, 2005, at 06:00 UT (or 06:07 UT Earth-receive time), Deep Impact released the impactor probe, which, using small thrusters, moved into the path of the comet, where it hit the following day, July 4, at 05:44:58 UT. The probe was traveling at a relative velocity of about 23,000 miles per hour (37,000 kilometers per hour) at the time of impact.

The impact generated an explosion the equivalent of 4.7 tons of TNT and a crater estimated to be about 490 feet (150 meters) in diameter.

Minutes after the impact, the flyby probe passed the nucleus at a range of about 310 miles (500 kilometers) and took images of the crater (although it was obscured by the dust cloud), ejecta plume, and the entire nucleus.

Simultaneous observations of the impact were coordinated with ground-based observatories as well as space-based ones, including the European Rosetta (which was about 50 million miles or 80 million kilometers from the comet), Hubble, Spitzer, the Swift X-ray telescope, and XMM-Newton.

The impactor also took images up to 3 seconds before impact that were transmitted via the flyby vehicle back to Earth.

Controllers registered about 4,500 images from the three cameras over the next few days. Based on the results of Deep Impacts investigations, scientists concluded that Comet Tempel 1 had probably originated in the Oort Cloud. The data also showed that the comet was about 75% empty space.

Although Deep Impacts primary mission was over, because the flyby vehicle still had plenty of propellant, on July 3, 2007, NASA approved a new supplemental mission for Deep Impact, known as EPOXI. The name was derived from the combination of the two components of this extended flight: Extrasolar Planet Observations (EPOCh) and Deep Impact Extended Investigation (DIXI).

This so-called mission of opportunity was originally focused on Comet 85P/Boethin. On July 21, 2005, Deep Impact was set on a trajectory to conduct a flyby of Earth in anticipation of intercepting Boethin. Unfortunately, scientists lost track of Comet Boethin, possibly because the comet had broken up.

Deep Impact was redirected toward Comet 103P/Hartley (or Hartley 2), starting with an engine burn on Nov. 1, 2007. EPOXIs new plan set Deep Impact on three consecutive Earth flybys, spread over two years (December 2007, December 2008, and June 2010) before the final trek to meet Comet Hartley 2.

These flybys essentially stole some energy from the spacecraft, thus dropping Deep Impact into a smaller orbit around the Sun.

Before the second Earth flyby, Deep Impact performed its EPOCh mission using the HRI instrument to perform photometric investigations of extrasolar planets around eight distant stars, returning nearly 200,000 images.

In the fall of 2010, Deep Impact began its investigations of Comet Hartley 2, conducting its flyby of the target at a range of about 430 miles (694 kilometers) at 15:00 UT Nov. 4, 2010. As with the encounter with Comet Tempel 1, Deep Impact used its three instruments to study Hartley 2 for three weeks.

Some of the images were so clear that scientists were able to identify jets of dust with particular features on the comets nucleus. The data showed that the two lobes of Hartley 2 were different in composition.

Once past this second cometary encounter, Deep Impact had little propellant for further cometary investigations, but there was a possibility that the spacecraft, if still in working condition, could be used for a flyby of Near Earth Asteroid 2002 GT in 2020.

With that goal in mind, thrusters were fired in December 2011 and October 2012 for targeting purposes. In the meantime, the spacecraft was used for the remote study of faraway comets such as C/200P1 (Garradd) in early 2012 and C/2012 S1 (ISON) in early 2013.

Communication with Deep Impact was lost sometime between Aug. 11 and Aug. 14, 2013, and after considerable effort to contact the spacecraft, NASA announced on Sept. 20, 2013, that it had officially abandoned efforts to contact Deep Impact.

NASA Deep Impact Mission Profile

NASA Jet Propulsion Laboratory: Deep Impact Page

Siddiqi, Asif A. Beyond Earth: A Chronicle of Deep Space Exploration, 1958-2016. NASA History Program Office, 2018.

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In Depth | Deep Impact (EPOXI) NASA Solar System Exploration

Injuries and slow start hurt the Comets in loss to Ortonville – Fergus Falls Daily Journal

Posted on October 19, 2022 by Danzig

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HALIFAX PLAYERS OF THE WEEK: Round two of new feature to spotlight top Comets – YourGV.com

Posted on October 19, 2022 by Danzig

Ive been a sportswriter going on six years now. In that time, Ive been called every name in the book, and a creative few I didnt know existed. Last year, after releasing my River City Sports All-District Football teams, a gentleman took to Twitter and called me the Rain Man of Danville/Pittsylvania County sports because I left a few players off the list he felt shouldve made it. I guess he didnt realize how smart Dustin Hoffmans Raymond Babbitt was and that he helped his brother, Tom Cruises Charles Babbitt, win $86,000 in Las Vegas.

Over the same list, I had another man leave me a message on the RCS Facebook page that featured language that wouldve made a sailor with Tourettes blush and was written in English so jumbled it could only be described as blibberish.

Its happened so much; Ive often thought about featuring a weekly Mean Tweets segment as shown on Jimmy Kimmel Live. However, Im smart enough to realize that like elbows, everybody has an opinion they are entitled to and that Im bound to tick somebody off by not choosing or highlighting little Johnny or Suzies perceived accomplishments.

When I released my inaugural Player of the Week segment last week, I expected my email account to fill up with comments and complaints such as the ones mentioned above. However, thats not what happened as Ive received nothing but great feedback over the column.

In that spirit, please enjoy Round 2 of the Halifax County High School Players of the Week.

Halifax County trekker Cheyenne Cline runs up hill at a meet earlier this year.

Girls cross country player of the week: Cheyenne Cline

Clines stock continued to rise last Wednesday at the Martinsville Piedmont District meet. Cline ran a 23:59.97 to finish ninth at the meet for her second consecutive Top-15 finish and her sixth of the year. Its also the fifth time the freshman has finished in the Top-10 with her highest placing coming at Tunstall where she checked in at seventh. She also finished ninth at the Comets meet at Bassett earlier this season.

With the season winding down, expect to see Cline making a run pun intended at both districts and regionals and maybe the Class 4 state tournament.

Halifax County cross country runner Brennan Hunt finishes a race at Smith River Complex earlier this season.

Boys cross country player of the week: Brennan Hunt

Along with Cline, Hunt continued to impress as he ran a 19:10.22 to finish 13th at Wednesdays Martinsville meet. The freshmans finish comes off the heels of his sixth place finish last week at Magna Vista where he ran a 20:55.15. It was the third consecutive meet where Hunt finished within the Top-15.

Similar to Cline, expect Hunt to make a run at both the district and regional tournaments.

Halifax County senior Kamyria Woody-Giggetts records a dig against Bassett last week.

Volleyball player of the week: Kamyria Woody-Giggetts

This was a tough race as several Halifax player were up for nomination. Junior Peyton Irby paced the Comets with seven kills against Bassett while Irby and junior Makayla Powell led with a pair of service aces. Defensively, Halifax was paced by senior Kamyria Woody-Giggetts eight digs while senior Jadyn Harlow checked in with seven against the Bengals. Junior Emma Payne recorded a team-high 10 assists.

Payne relinquished the top spot in assists against Mecklenburg County to Harlow who led with six while Irby and senior Shamya Hankins finished close behind with four. Junior Erin Satterfield led with a team-high seven kills while Hankins, Irby and Harlow were close behind with four apiece against the Phoenix. Defensively, Woody-Giggetts led with a team-high 10 digs.

Defense wins championships and with Woody-Giggetts leading the way in all three matches, her selection as Player of the Week just felt natural.

Halifax Countys Javeion Gooden makes a tackle in the Comets non-district matchup against Jefferson Forest earlier this season.

Football player of the week: Javeion Gooden

Really, Halifaxs entire defensive line shouldve been given this award as a collective and as I write this right now, Goodens individual selection may change by the time I get done writing this.

Gooden, a senior, was all over the field this past Friday against rival George Washington, making tackles at will. Going through my photos Sunday morning, it seemed all I saw was Gooden, along with fellow seniors Ahmad Moon, Semaj Jeffreys and Jyquez Ferrell, making stops on GW ballcarriers.

The Comets defense forced the Eagles into a pair of turnover on downs in the second half and made a pair of red zone stops to keep GW out of the end zone in the third and fourth quarters in Halifaxs close loss this past Friday.

At the end, after hard thought, Goodens individual selection stands as he serves a solid leadership role for the Comets.

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HALIFAX PLAYERS OF THE WEEK: Round two of new feature to spotlight top Comets - YourGV.com

Kevin Dineen and imon Nemec on Uticas team strengths prior to season-opener Saturday – WUTR/WFXV – CNYhomepage.com

Posted on October 19, 2022 by Danzig

UTICA, N.Y. (WUTR/WFXV/WPNY) Utica Comets Head Coach Kevin Dineen spoke to the media for the first time this season on Thursday morning, he was then followed by 2022 NHL Entry Draft number two overall selection imon Nemec, who had his first day of practice with the AHL squad after being sent down on Wednesday in exchange for fellow defenseman Kevin Bahl.

In his availability, Coach Dineen named his Captains for the upcoming season, Ryan Schmelzer will wear the C for the second consecutive year while Robbie Russo, Joe Gambardella, and Tyler Wotherspoon will be the Alternates. He also revealed that Akira Schmid will be the teams opening night starter, but that going into every game he is confident in his netminder pairing which includes Schmid and Nico Daws.

From @UticaComets Head Coach Kevin Dineen this morning:

Ryan Schmelzer will return as our Captain, Joe Gambardella, Robbie Russo and Tyler Wotherspoon will be our leadership group.

He added, I think we have players that are much more vocal that Ryan, infectious in the way they are around the locker room, but we feel that Ryan represents how we conduct ourselves on and off the ice. I think he plays with heart and passion on a nightly basis, hes a gamer.

Nemec took to the stand next, answering questions for the first time as a Comet. He started by giving the media a pronunciation of his name (Shee-mone Nyee-mits), followed that with some elaboration about the differences between the European and North American games, mainly rink size and physicality, and said that hes heard about the passion of Comets fans already before rounding out his availability with a vote of confidence, I know [the] players I know [the] coaches, I know all the staff, I think it will be good.