Department of Genetic Medicine | Johns Hopkins Medicine

The McKusick-Nathans Institute of Genetic Medicine | Department of Genetic Medicineseeks to further the understanding of human heredity and genetic medicine and use that knowledge to treat and prevent disease.

The Department of Genetic Medicineis working to consolidate all relevant teaching, patient care and research in human and medical genetics at Johns Hopkins to provide national and international leadership in genetic medicine. The Department of Genetic Medicineserves as a focal point for interactions between diverse investigators to promote the application of genetic discoveries to human disease and genetics education to the public. It builds upon past strengths and further develops expertise in the areas of genomics, developmental genetics and complex disease genetics. The Department of Genetic Medicineworks to catalyze the spread of human genetic perspectives to other related disciplines by collaboration with other departments within Johns Hopkins.

There are more than 300 dedicated employees in the Department of Genetic Medicine, fulfilling the Johns Hopkins tripartite mission of research, teaching and patient care. They include 45 full-time faculty, 15 residents, more than 70 graduate students and 200 staff.

All too often, when we see injustices, both great and small, we think, that's terrible, but we do nothing. We say nothing. We let other people fight their own battles. We remain silent because silence is easier. Qui tacet consentire videtur is Latin for 'Silence gives consent.' When we say nothing, when we do nothing, we are consenting to these trespasses against us.Roxane Gay

The indifferent and arrogant murder of George Floyd is but one of many searing examples of racism, oppression and sheer wickedness imposed on members of the African-American community over the last 400 years. Repeatedly, over these many years, periods of apparent progress have been undercut by horrific acts of racially-based evil that expose an underlying hard core of racial bias and systematic racism. The sadness, anger and frustration we all feel are compounded by the failure of our society to respond to these events with real and sustained justice. We cannot, however, let these events undermine our quest for meaningful and sustained progress towards correcting the systemic problems and beliefs leading to these events. To quote Martin Luther King Jr., Change does not roll in on the wheels of inevitability, but comes through continuous struggle.

How can we break out of this cycle of modest progress punctuated by horrific failures? The answers to this question are neither simple nor obvious. Success will require a sustained and multi-faceted effort from all of us. Some reactions seem obvious and personally attainable; we must treat all members of our society equally and fairly. In these difficult times, we much reach out to those directly affected with understanding, respect, and support. All of us must commit to and participate in these positive interactions. Beyond these responses of the moment, we must search for ways that we can change the social, economic and personal environment to minimize the likelihood of recurrence and maximize progress towards real equality for all. As geneticists, we treasure diversity and understand many of the biological factors underlying it. Perhaps, one special responsibility for us is to help others in society understand and value diversity and individuality.

As members of the Human Genetics program and Department of Genetic Medicine community, we recognize there are some among us who are more vulnerable to the biases illuminated by the death of George Floyd and many, many others; whose fear of an encounter with the police is amplified by personal and community experience; and whose experience of pain and suffering far exceeds what most of us can fully understand. To those most vulnerable in our Department of Genetic Medicinefamily, we stand with you and raise our voices to support you. We are ready to listen and act in pursuit of a learning environment of which you can be proud and a world into which you will move and feel free to change.

Finally, as we search for appropriate responses, we are grateful to have your voices, your guidance to help illuminate a path forward. We recognize and are encouraged by the outpouring of activism, passion, rage and love from our students, our department, our community and even our own families. We also recognize that this journey, which began centuries ago, will be long, sometimes uncomfortable and inelegant and studded with setbacks. We are, however, committed to do everything in our power to speed its progress.

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Department of Genetic Medicine | Johns Hopkins Medicine

Genetic Medicine | Internal Medicine | Michigan Medicine …

As use of genomic technologies continue to increase in research and clinical settings, the Division of Genetic Medicine serves a key role in bringing together basic, clinical, and translational expertise in genomic medicine, with multidisciplinary faculty comprised of MDs, PhD scientists, and genetic counselors. Demand for expertise in genetics continues to increase, and the Division of Genetic Medicine is committed to advancing scientific discovery and clinical care of patients.

In addition to our Medical Genetics Clinic, genetics services are available through several other Michigan Medicine clinics and programs, including the Breast and Ovarian Cancer Risk Evaluation Program, Cancer GeneticsClinic,Inherited Cardiomyopathies and Arrhythmias Program,Neurogenetics Clinic, Pediatric Genetics Clinic, and Prenatal Evaluation Clinic.

Our faculty are focused on various research areas including cancer genetics, inherited hematologic disorders, neural stem cells,the mechanisms and regulation of DNA repair processes in mammalian cells, predictive genetic testing,understanding the mechanisms controlled by Hox genes, birth defects, bleeding and thrombotic disorders, and human limb malformations.

Division of Genetic Medicinefaculty are actively engaged in the education, teaching, and mentorship of clinicians, and clinical and basic scientists, including undergraduate and graduate students, medical students, residents, and fellows from various subspecialties.

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Genetic Medicine | Internal Medicine | Michigan Medicine ...

Genetic Medicine | Department of Medicine

Advances in molecular biology and human genetics, coupled with the completion of the Human Genome Project and the increasing power of quantitative genetics to identify disease susceptibility genes, are contributing to a revolution in the practice of medicine. In the 21st century, practicing physicians will focus more on defining genetically determined disease susceptibility in individual patients. This strategy will be used to prevent, modify, and treat a wide array of common disorders that have unique heritable risk factors such as hypertension, obesity, diabetes, arthrosclerosis, and cancer.

The Division of Genetic Medicine provides an academic environment enabling researchers to explore new relationships between disease susceptibility and human genetics. The Division of Genetic Medicine was established to host both research and clinical research programs focused on the genetic basis of health and disease. Equipped with state-of-the-art research tools and facilities, our faculty members are advancing knowledge of the common genetic determinants of cancer, congenital neuropathies, and heart disease. The Division faculty work jointly with the Vanderbilt-Ingram Cancer Center to support the Hereditary Cancer Clinic for treating patients and families who have an inherited predisposition to various malignancies.

Genetic differences in humans at the molecular level not only contribute to the disease process but also significantly impact an individuals ability to respond optimally to drug therapy. Vanderbilt is a pioneer in precisely identifying genetic differences between patients and making rational treatment decisions at the bedside.


Genetic Medicine | Department of Medicine

Genomics and Medicine – Genome.gov

It has often been estimated that it takes, on average, 17years to translate a novel research finding into routine clinical practice. This time lag is due to a combination of factors, including the need to validate research findings, the fact that clinical trials are complex and take time to conduct and then analyze, and because disseminating information and educating healthcare workers about a new advance is not an overnight process.

Once sufficient evidence has been generated to demonstrate a benefit to patients, or "clinical utility," professional societies and clinical standards groups will use that evidence to determine whether to incorporate the new test into clinical practice guidelines. This determination will also factor in any potential ethical and legal issues, as well economic factors such as cost-benefit ratios.

The NHGRIGenomic Medicine Working Group(GMWG) has been gathering expert stakeholders in a series of genomic medicine meetingsto discuss issues surrounding the adoption of genomic medicine. Particularly, the GMWG draws expertise from researchers at the cutting edge of this new medical toolset, with the aim of better informing future translational research at NHGRI. Additionally the working group provides guidance to theNational Advisory Council on Human Genome Research (NACHGR)and NHGRI in other areas of genomic medicine implementation, such as outlining infrastructural needs for adoption of genomic medicine, identifying related efforts for future collaborations, and reviewing progress overall in genomic medicine implementation.

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Genomics and Medicine - Genome.gov

Blood lipid levels may be altered in some autistic people – Spectrum

Blood biomarker: Levels of lipids, such as cholesterol and triglycerides, may be altered in a subgroup of people with autism.

Sebastian Kaulitzki / Science Photo Library / Getty Images

Nearly 7 percent of autistic people in the United States have abnormal blood levels of fatty compounds called lipids, according to a study published today in Nature Medicine1. The studys approach, drawing on multiple datasets, could help researchers parse autism into subtypes, the researchers say.

Past studies have shown a link between this metabolic condition, called dyslipidemia, and autism in people with rare genetic conditions2.But this is the first in-depth, multidimensional analysis to establish a robust association with autism more broadly, says Yuan Luo, study investigator and associate professor of preventive medicine at Northwestern University in Chicago, Illinois.

The study used a comprehensive approach integrating large datasets, including healthcare claims, electronic health records, familial gene sequences and an atlas of developmental gene-expression patterns.

Just as combining geographical data from various maps can help navigation tools create a more comprehensive view of the world, integrating datasets about various facets of autism can help us better understand the condition, says lead investigator Isaac Kohane, professor of biomedical informatics at Harvard University.

Using one modality gives you only one perspective, whereas using multiple modalities gives you a holistic perspective, he says.

Autism is a highly varied condition, with multiple genetic and environmental influences. Analyzing large and diverse datasets can help researchers parse the condition into smaller subgroups with shared phenotypes and devise bespoke treatments, Kohane says.

The new work may also help clinicians identify biological markers for screening autistic children early in development, rather than relying on behavioral traits.

This is important because currently autism diagnosis is only based on symptoms. But when you actually see these symptoms, its already too late, Luo says. [These findings] could be of immediate clinical utility, and we plan to directly test those by future studies, including clinical trials.

First the team mapped out how genes work in concert during prenatal human brain development, a critical time window for autism. They used the BrainSpan online atlas to obtain data on the expression patterns of exons the parts of genes that code for proteins in 26 brain regions. They then narrowed in on clusters of exons that are expressed differently between boys and girls, given sex differences seen in autism.

Next, the researchers identified autism-related mutations found in the exons of autistic people. To do so, they searched a database of genetic sequences for 3,531 people from 50 families with two to five autistic children, looking for mutations shared by all autistic siblings within each family, as well as 1,704 families with autistic and unaffected sibling pairs, focusing on the mutations found only in the children with autism.

They then looked for overlaps between the exon clusters identified via the atlas and those with autism mutations, identifying 33 in common. Some contain the exons of genes involved in lipid protein regulation; mutations in them could lead to low levels of lipoproteins, cholesterol and triglycerides in the blood. The findings point to a possible association between autism and dyslipidemia, the researchers say.

To test this theory, the team analyzed medical records of 2.75 million people at Boston Childrens Hospital in Massachusetts, 25,514 of whom are children with autism. As a group, autistic children show significant alterations in blood lipid profiles compared with age-matched controls. For example, children with autism have higher triglyceride levels, regardless of age, medication, sex or metabolic conditions, such as obesity or diabetes.

The team examined healthcare claims for more than 34 million people across the United States, including 80,714 autistic people. They found that 6.6 percent of people with autism have dyslipidemia.

The study also found that parents with a history of dyslipidemia have up to 16 percent greater odds of having autistic children a result the researchers hope to investigate further in future studies, Luo says.

The findings jibe with previous research showing that dyslipidemia-associated genes are involved with several mechanisms key to neuronal function, such as controlled cell death.

However, its still unclear how lipids may affect the human brain, says Michael Snyder, professor of genetics at Stanford University in Palo Alto, California, who was not involved in the study. More research manipulating lipid levels by either knocking out dyslipidemia-associated genes in mice or using medication may offer a clearer understanding of this association.

In particular, researchers should try using lipid-lowering drugs, such as statins, in autistic people with dyslipidemia to determine whether the treatment improves their lipid levels and eases autism traits, Snyder says.

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Blood lipid levels may be altered in some autistic people - Spectrum

LogicBio Therapeutics Reports Second Quarter 2020 Financial Results and Provides Business UpdatesFDA Clears IND Application for LB-001 for the…

LEXINGTON, Mass., Aug. 10, 2020 (GLOBE NEWSWIRE) -- LogicBio Therapeutics, Inc. (Nasdaq:LOGC) (LogicBio or the Company), a company dedicated to extending the reach of genetic medicine with pioneering targeted delivery platforms, today reported financial results for the quarter ended June 30, 2020, provided a business update and announced the U.S. Food and Drug Administration (FDA) has cleared the Companys Investigational New Drug (IND) application for LB-001 for the treatment of methylmalonic acidemia in pediatric patients. LogicBio released a separate press release this morning providing further details on the planned Phase 1/2 clinical design for LB-001.

We are thrilled to have received clearance to move forward with this first-in-human clinical trial with our lead product candidate, LB-001, for the treatment of methylmalonic acidemia, a life-threatening congenital genetic disease with no current therapeutic treatment options. This represents a significant milestone in our goal of bringing a treatment to MMA patients as well as for our GeneRide platform. We have maintained continuous dialogue with the centers of excellence that are planned to participate in the Phase 1/2 clinical trial, and we look forward to activating these sites as quickly as possible, said Fred Chereau, CEO of LogicBio. We have instituted systems attempting to mitigate COVID-19 dynamics on our study start-up process and, based on our best estimates, we plan to enroll our first patient in early 2021.

Commenting on the Next Generation Capsid Program, Mr. Chereau said, We are very excited about the recent advances in our novel capsid program, which has generated liver-tropic capsids intended for use in gene editing technologies such as GeneRide and other gene therapy approaches. We are focused on executing across all of our programs and look forward to sharing further details on our novel capsids in early 2021.

Appointment of Daniel Gruskin, M.D. to SVP, Head of Clinical Development

Daniel Gruskin, M.D. was appointed as SVP, head of clinical development in August 2020. Dr. Gruskin has served as interim head of clinical development of LogicBio since June 2020. In April 2020, Dr. Gruskin started consulting with the Company as a special advisor. Previously, Dr. Gruskin served in roles of increasing responsibility at Sanofi Genzyme, most recently as vice president, head of global medical affairs, rare disease, in which capacity he oversaw medical affairs, life cycle management, scientific affairs and other medical and development activities related to metabolic, rare and/or genetic diseases. Prior to his role at Sanofi Genzyme, Dr. Gruskin served as assistant professor, human genetics and pediatrics at Emory University School of Medicine, where he was also the chief of the genetics section at Childrens Healthcare of Atlanta.

Daniel has been instrumental in leading LB-001 clinical development efforts including getting the IND cleared. His deep experience in genetic medicines and metabolic diseases will serve LogicBio well as we look to execute on our goals for both the GeneRide and Next Generation Capsid platforms in search of transformative medicines, said Mr. Chereau.

Anticipated Milestones for 2020 and 2021:

Second Quarter 2020 Financial Results

Three Months Ended June 30, 2020 and 2019

About LogicBio Therapeutics

LogicBio Therapeuticsis dedicated to extending the reach of genetic medicine with pioneering targeted delivery platforms.

LogicBios proprietary genome editing technology platform, GeneRide, enables the site-specific integration of a therapeutic transgene without nucleases or exogenous promoters by harnessing the native process of homologous recombination. LogicBio has received FDA clearance for the first-in-human clinical trial of LB-001, a wholly owned genome editing program leveraging GeneRide for the treatment of methylmalonic acidemia. Patient enrollment is expected to begin in early 2021. In addition, LogicBio has a collaboration with Takeda to research and develop LB-301, an investigational therapy leveraging GeneRide for the treatment of the rare pediatric disease Crigler-Najjar syndrome.

LogicBio is also developing a Next Generation Capsid platform for use in gene editing and gene therapies. Data presented have shown that the capsids deliver highly efficient functional transduction of human hepatocytes with improved manufacturability with low levels of pre-existing neutralizing antibodies in human samples. Top-tier capsid candidates from this effort demonstrated significant improvements over benchmark AAVs currently in clinical development. LogicBio is developing these highly potent vectors for internal development candidates and potentially for business development collaborations.

LogicBio is headquartered inLexington, Mass. For more information, please visitwww.logicbio.com.

Forward Looking Statements

This press release contains forward-looking statements within the meaning of the federal securities laws, including those related to the Companys plans to initiate, advance and complete its planned SUNRISE Phase 1/2 clinical trial of LB-001 in MMA; the timing, progress and results of the Companys research and development activities, including those related to the GeneRide technology platform and Next Generation Capsid Program; its plans for LB-301 in Crigler-Najjar; and the sufficiency of its cash and cash equivalents to fund operating expenses and capital expenditure requirements. These are not statements of historical facts and are based on managements beliefs and assumptions and on information currently available. They are subject to risks and uncertainties that could cause the actual results and the implementation of the Companys plans to vary materially, including the risks associated with the initiation, cost, timing, progress and results of the Companys current and future research and development activities and preclinical studies and potential future clinical trials. In particular, the impact of the COVID-19 pandemic on the Companys ability to progress with its research, development, manufacturing and regulatory efforts, including the Companys plans to initiate, advance and complete its Phase 1/2 clinical trial for LB-001 in MMA, and the value of and market for the Companys common stock, will depend on future developments that are highly uncertain and cannot be predicted with confidence at this time, such as the ultimate duration of the pandemic, travel restrictions, quarantines, social distancing and business closure requirements in the United States and in other countries, and the effectiveness of actions taken globally to contain and treat the disease. These risks are discussed in the Companys filings with the U.S. Securities and Exchange Commission (SEC), including, without limitation, the Companys Annual Report on Form 10-K filed on March 16, 2020 with the SEC, the Companys Quarterly Report on Form 10-Q filed on May 11, 2020, and the Companys subsequent Quarterly Reports on Form 10-Q and other filings with the SEC. Except as required by law, the Company assumes no obligation to update these forward-looking statements publicly, even if new information becomes available in the future.


Investors:Brian LuqueAssociate Director, Investor Relationsbluque@logicbio.com951-206-1200

Media:Stephanie SimonTen Bridge CommunicationsStephanie@tenbridgecommunications.com617-581-9333


LogicBio Therapeutics Reports Second Quarter 2020 Financial Results and Provides Business UpdatesFDA Clears IND Application for LB-001 for the...

New Approach to Treating Osteoarthritis Advances | NYU Langone News – NYU Langone Health

Injections of a natural energy molecule prompted regrowth of almost half of the cartilage lost with aging in knees, a new study in rodents shows.

The study results revolve around the long-established idea that machines within animal and human cells turn the sugars, fats, and proteins we eat into energy used by the bodys millions of cells. The molecule most used to store that energy is called adenosine triphosphate, or ATP. Along with this central role in metabolism, adenosine also helps signal other cells and serves as a building block of genetic material, and so is central to the growth of human tissue.

Previous research had shown that maintaining supplies of adenosine, known to nourish the chondrocyte cells that make cartilage, also prevented osteoarthritis in similar animal models of the disease.

In the new NYU Grossman School of Medicineled study, researchers injected adenosine into the joints of rodents whose limbs had been damaged by inflammation resulting from either traumatic injury, such as a torn ligament, or from massive weight gain placing pressure on joints. The biological damage in these cases is similar, researchers say, to that sustained in human osteoarthritis.

Published online in the journal Scientific Reports on August 10, the study rodents received 8 weekly injections of adenosine, which prompted regrowth rates of cartilage tissue between 50 percent and 35 percent as measured by standard laboratory scores.

Our latest study shows that replenishing adenosine stores by injection works well as a treatment for osteoarthritis in animal models of the disease, and with no apparent side effects, says lead study author Carmen Corciulo, PhD, a postdoctoral fellow at NYU Langone.

Dr. Corciulo says it is too soon to use this experimental model as a therapy in people. Clinical trials must await a test drug that can be safely stored for days if not weeks, and experiments in larger mammals.

Study senior investigator Bruce N. Cronstein, MD, the Dr. Paul R. Esserman Professor of Medicine at NYU Langone Health, says the teams research is important because the few existing drug therapies for osteoarthritis such as acetaminophen and COX-2 inhibitor drugs, including naproxen and ibuprofen, only numb joint pain, or like hyaluronic acid just lubricate its tissues. None stall disease progression or reverse the damage. Painkillers, such as opioids, are often prescribed, but are also highly addictive, he cautions.

People with osteoarthritis desperately need more treatment options with fewer side effects, and our research advances that effort, says Dr. Cronstein, who also serves as the director of NYU Langones Clinical and Translational Science Institute. He notes that other experimental medications are being developed elsewhere, including parathyroid hormone to stimulate bone growth, WNT inhibitor drugs to block the bone and cartilage degradation, and growth factor chemicals to promote cartilage growth.

Dr. Cronstein, Dr. Corciulo, and NYU Grossman School of Medicine have a patent application pending for the use of adenosine and other agents that help with its binding to chondrocytes, called A2A receptor agonists, for the treatment of osteoarthritis.

Among the studys other key findings was that a cell-signaling pathway, known as transforming growth factor beta (TGF-beta) and involved in many forms of tissue growth, death, and differentiation, was highly active in cartilage tissue damaged by osteoarthritis, as well as in cartilage tissue undergoing repair after being treated with adenosine. Additional testing in lab-grown chondrocytes from people with osteoarthritis showed different chemical profiles of TGF-beta signaling during breakdown than during growth, providing the first evidence that the pathway switched function in the presence of adenosine (from assisting in cartilage breakdown to encouraging its repair.)

Developing treatments to halt or slow the disease is important, Dr. Cronstein says, because well over 100 million people worldwide are estimated to have osteoarthritis, which is tied to aging, especially in women. This figure, he says, is only expected to grow as more people live longer and obesity rates climb.

Right now, the only way to stop osteoarthritis is to have affected joints surgically replaced, which not only comes with pain and risk of infection, but is also quite costly, says Dr. Cronstein. If new therapies can delay or prevent disease onset and progression, then fewer joint replacements will save people from a lot of pain and expense.

The study was funded by National Institutes of Health grants R01 AR056672 and R01 AR068593, NYU-HHC Clinical and Translational Science Institute grant UL1 TR000038, and the Arthritis Foundation.

Dr. Corciulo and Dr. Cronstein have a patent for the methods and compositions for treating osteoarthritis and promoting cartilage formation (U.S. Patent 10,441,541), which has been assigned to NYU Grossman School of Medicine. They are cofounders of Regenosine Inc., a company that is developing new treatments for osteoarthritis, and in which they hold a financial interest. Dr. Cronstein has consulted for Eli Lilly, Horizon Pharmaceuticals, Bristol Myers Squibb, and Astrazeneca. He also has grants from Arcus Biopharma. All relationships are being managed in accordance with the policies and practices of NYU Langone.

Besides Dr. Cronstein and Dr. Corciulo, other NYU Langone investigators involved in this study are Cristina Castro, MD; Thomas Coughlin, PhD; Samson Jacob, MS; David Fenyo, PhD; Daniel B. Rifkin, PhD; and Oran Kennedy, PhD.

David MarchPhone: 212-404-3528david.march@nyulangone.org

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New Approach to Treating Osteoarthritis Advances | NYU Langone News - NYU Langone Health

Californian company claims ‘advantages over other vaccines and therapies’ for COVID-19 – The Pharma Letter

Ligandal, a genetic medicine company that uses nanotechnology to develop targeted and personalized therapies,

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Californian company claims 'advantages over other vaccines and therapies' for COVID-19 - The Pharma Letter

Stoke Therapeutics Reports Second Quarter Financial Results and Provides Business Updates – Business Wire

BEDFORD, Mass.--(BUSINESS WIRE)--Stoke Therapeutics, Inc. (Nasdaq: STOK), a biotechnology company pioneering a new way to treat the underlying cause of genetic diseases by precisely upregulating protein expression, today reported financial results for the second quarter of 2020 and provided business updates.

Today we are announcing that the first patient has been dosed with STK-001, which we believe has the potential to be the first-disease modifying medicine for Dravet syndrome, a severe and progressive genetic epilepsy that is characterized by developmental delays and cognitive impairment, in addition to seizure activity, said Edward M. Kaye, M.D., Chief Executive Officer of Stoke Therapeutics. The start of MONARCH also marks Stokes official transition to a clinical-stage biotech company. We enter this new stage in a strong financial position to execute on our plans for STK-001 in Dravet syndrome and continue to advance the potential of our TANGO platform for additional genetic diseases.

Second Quarter 2020 Business Highlights and Recent Developments

Upcoming Anticipated Milestones

Second Quarter and Year-to-Date Results

About STK-001

STK-001 is an investigational new medicine for the treatment of Dravet syndrome. Stoke believes that STK-001, a proprietary antisense oligonucleotide (ASO), has the potential to be the first disease-modifying therapy to address the genetic cause of Dravet syndrome. STK-001 is designed to upregulate NaV1.1 protein expression by leveraging the non-mutant (wild-type) copy of the SCN1A gene to restore physiological NaV1.1 levels, thereby reducing both occurrence of seizures and significant non-seizure comorbidities. Stoke has generated preclinical data demonstrating proof-of-mechanism and proof-of-concept for STK-001. STK-001 has been granted orphan drug designation by the FDA as a potential new treatment for Dravet syndrome.

About Phase 1/2a Clinical Study (MONARCH)

The MONARCH study is a Phase 1/2a open-label study of children and adolescents ages 2 to 18 who have an established diagnosis of Dravet syndrome and have evidence of a pathogenic genetic mutation in the SCN1A gene. The primary objectives for the study will be to assess the safety and tolerability of STK-001, as well as to characterize human pharmacokinetics. A secondary objective will be to assess the efficacy as an adjunctive antiepileptic treatment with respect to the percentage change from baseline in convulsive seizure frequency over a 12-week treatment period. Stoke also intends to measure non-seizure aspects of the disease, such as quality of life as secondary endpoints. Stoke plans to enroll approximately 40 patients across 20 sites in the United States.

About Dravet Syndrome

Dravet syndrome is a severe and progressive genetic epilepsy characterized by frequent, prolonged and refractory seizures, beginning within the first year of life. Dravet syndrome is difficult to treat and has a poor long-term prognosis. Complications of the disease often contribute to a poor quality of life for patients and their caregivers. The effects of the disease go beyond seizures and often include severe intellectual disabilities, severe developmental disabilities, motor impairment, speech impairment, autism, behavioral difficulties and sleep abnormalities. Compared with the general epilepsy population, people living with Dravet syndrome have a higher risk of sudden unexpected death in epilepsy, or SUDEP. Dravet syndrome affects approximately 35,000 people in the United States, Canada, Japan, Germany, France and the United Kingdom, and it is not concentrated in a particular geographic area or ethnic group.

About Stoke Therapeutics

Stoke Therapeutics (Nasdaq: STOK) is a biotechnology company pioneering a new way to treat the underlying causes of severe genetic diseases by precisely upregulating protein expression to restore target proteins to near normal levels. Stoke aims to develop the first precision medicine platform to target the underlying cause of a broad spectrum of genetic diseases in which the patient has one healthy copy of a gene and one mutated copy that fails to produce a protein essential to health. These diseases, in which loss of approximately 50% of normal protein expression causes disease, are called autosomal dominant haploinsufficiencies. Stoke is headquartered in Bedford, Massachusetts with offices in Cambridge, Massachusetts. For more information, visit https://www.stoketherapeutics.com/ or follow the company on Twitter at @StokeTx.

Cautionary Note Regarding Forward-Looking Statements

This press release contains forward-looking statements within the meaning of the safe harbor provisions of the Private Securities Litigation Reform Act of 1995, including, but not limited to: future operating results, financial position and liquidity, the direct and indirect impact of COVID-19 on our business, financial condition and operations, including on our expenses, supply chain, strategic partners, research and development costs, clinical trials and employees; our expectation about timing and execution of anticipated milestones, responses to regulatory authorities, expected nomination of a second product candidate and timing thereof, and our ability to use study data to advance the development of STK-001; the ability of STK-001 to treat the underlying causes of Dravet syndrome; and the ability of TANGO to design medicines to increase protein production and the expected benefits thereof. These forward-looking statements may be accompanied by such words as aim, anticipate, believe, could, estimate, expect, forecast, goal, intend, may, might, plan, potential, possible, will, would, and other words and terms of similar meaning. These forward-looking statements involve risks and uncertainties, as well as assumptions, which, if they do not fully materialize or prove incorrect, could cause our results to differ materially from those expressed or implied by such forward-looking statements. These statements involve risks and uncertainties that could cause actual results to differ materially from those reflected in such statements, including: our ability to develop, obtain regulatory approval for and commercialize STK-001 and future product candidates; the timing and results of preclinical studies and clinical trials; the risk that positive results in a clinical trial may not be replicated in subsequent trials or success in early stage clinical trials may not be predictive of results in later stage clinical trials; risks associated with clinical trials, including our ability to adequately manage clinical activities, unexpected concerns that may arise from additional data or analysis obtained during clinical trials, regulatory authorities may require additional information or further studies, or may fail to approve or may delay approval of our drug candidates; the occurrence of adverse safety events; failure to protect and enforce our intellectual property, and other proprietary rights; failure to successfully execute or realize the anticipated benefits of our strategic and growth initiatives; risks relating to technology failures or breaches; our dependence on collaborators and other third parties for the development, regulatory approval, and commercialization of products and other aspects of our business, which are outside of our full control; risks associated with current and potential delays, work stoppages, or supply chain disruptions caused by the coronavirus pandemic; risks associated with current and potential future healthcare reforms; risks relating to attracting and retaining key personnel; failure to comply with legal and regulatory requirements; risks relating to access to capital and credit markets; environmental risks; risks relating to the use of social media for our business; and the other risks and uncertainties that are described in the Risk Factors section of our most recent annual or quarterly report and in other reports we have filed with the U.S. Securities and Exchange Commission. These statements are based on our current beliefs and expectations and speak only as of the date of this press release. We do not undertake any obligation to publicly update any forward-looking statements.

Financial Tables Follow





































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Stoke Therapeutics Reports Second Quarter Financial Results and Provides Business Updates - Business Wire

Here’s Why Shares of Editas Medicine and Beam Therapeutics Are Soaring Today – Motley Fool

What happened

Shares of Editas Medicine (NASDAQ:EDIT) and Beam Therapeutics (NASDAQ:BEAM) rose as much as 23% and 29%, respectively, today after the pair were rumored to be considering a merger. Although investors shouldn't invest based on speculation, a merger would make sense on multiple fronts.

The duo already have an agreement in place to collaborate on genetic medicines, but the struggling pipeline of Editas Medicine could receive a significant boost from Beam Therapeutics. It would also allow Editas shareholders to avoid many of the technical pitfalls of first-generation CRISPR gene-editing tools, which have yet to be adequately reflected in stock prices. Of course, the flip side is that the merger doesn't make as much sense for Beam Therapeutics.

As of 12:50 p.m. EDT, both small-cap stocks had settled to gains of about 14%.

Image source: Getty Images.

There are multiple reasons a merger makes sense. Consider that:

There's not much to the report that Editas Medicine and Beam Therapeutics are considering a merger. Only one digital publication mentions "chatter" without providing any follow-up details. The rumors are at least plausible given the ties to the Broad Institute and overlap of the scientific founders, but investors simply don't have much to go on. That said, a merger would make more sense for Editas Medicine than Beam Therapeutics, as the latter has a much stronger technical foundation to lean on for the long haul.

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Here's Why Shares of Editas Medicine and Beam Therapeutics Are Soaring Today - Motley Fool

Grant will fund study into COVID outcome disparities in NYC – Cornell Chronicle

Weill Cornell Medicines Clinical and Translational Science Center (CTSC) has been awarded a grant from the National Institutes of Health to investigate the role of social and biological factors in determining COVID-19 severity and outcomes in New York City patients.

The two-year, $1.5 million grant will fund projects led by Dr. Julianne Imperato-McGinley, director of the CTSC and The Abby Rockefeller Mauz Distinguished Professor of Endocrinology in Medicine at Weill Cornell Medicine.

The projects co-leaders are Dr. Olivier Elemento, director of the Englander Institute for Precision Medicine and professor of computational genomics in pathology and laboratory medicine at Weill Cornell; and Dr. Said Ibrahim, professor of health care policy and research and senior associate dean for diversity and inclusion at Weill Cornell.

Black and Latino populations have suffered a significantly higher proportion of infection and death from COVID-19 in New York City and across the country. Social determinants of health including lack of access to adequate medical care, crowded housing and exposure from ones occupation can influence the likelihood of acquiring COVID-19.

Co-morbidities such as obesity, diabetes and lung and heart disease that put people at risk for severe illness are also more common in Black and Latino populations.

To assess how socioeconomic factors have contributed to the racial and ethnic disparities, the investigators will compare rates of hospitalization, intensive care unit admissions and deaths from COVID-19 in affluent versus lower income communities within New York City. They will also use data from patients across the NewYork-Presbyterian Hospital system to study patterns in demographics, laboratory results and biospecimens to determine if theres a link between genetic variability, race and ethnicity and severity of COVID-19.

The project builds on Weill Cornell Medicines vision of a clinical research program that combines clinical care, investigation into social determinants of health and basic science research. Leveraging CTSC infrastructure, this approach brings together sources like census and other government data, electronic health records and the institutions newly created biobank of COVID-19 patient specimens.

The team plans to use its findings to build a model to predict who is most susceptible to the disease, which can help shape prevention and treatment strategies and bring precision medicine to COVID-19 patients. The team also aims to expand its work to regional and national analyses, tapping into a database of clinical data from COVID-19 patients that is being assembled by the Clinical and Translational Science Award program national network.

Bridget Kuehn is a freelance writer for Weill Cornell Medicine.

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Grant will fund study into COVID outcome disparities in NYC - Cornell Chronicle

NIH taps Dr. Lindsey Criswell as director of the National Institute of Arthritis and Musculoskeletal and Skin Diseases – National Institutes of Health

News Release

Thursday, August 6, 2020

National Institutes of Health Director Francis S. Collins, M.D., Ph.D., has selected Lindsey A. Criswell, M.D., M.P.H., D.Sc., as director of NIHs National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS). A rheumatologist, Dr. Criswell is currently the vice chancellor of research at the University of California, San Francisco (UCSF). She is a professor of rheumatology in UCSFs Department of Medicine, as well as a professor of orofacial sciences in its School of Dentistry. She is expected to begin her new role as the NIAMS director in early 2021. She will succeed long-time directorStephen I. Katz, M.D., Ph.D., who passed away suddenly in December 2018.

Dr. Criswell has rich experience as a clinician, researcher and administrator. Her ability to oversee the research program of one of the countrys top research-intensive medical schools, and her expertise in autoimmune diseases, including rheumatoid arthritis and lupus, make her well-positioned to direct NIAMS, said Dr. Collins. I look forward to having her join the NIH leadership team early next year. I also want to thank Robert H. Carter, M.D., for his exemplary work as the acting director of NIAMS since December 2018.

As NIAMS director, Dr. Criswell will oversee the institutes annual budget of nearly $625 million, which supports research into the causes, treatment and prevention of arthritis and musculoskeletal and skin diseases. The institute advances health through biomedical and behavioral research, research training and dissemination of information on research progress in these diseases.

The NIAMS Division of Extramural Research supports scientific studies and research training and career development throughout the country through grants and contracts to research organizations in fields that include rheumatology, muscle biology, orthopaedics, bone and mineral metabolism and dermatology. NIAMS-supported research addresses some of the most common and disabling chronic diseases that affect almost every household in America.

Dr. Criswell has been a principal investigator on multiple NIH grants since 1994 and has published more than 200 peer-reviewed journal papers. Her research focuses on the genetics and epidemiology of human autoimmune disease, particularly rheumatoid arthritis and systemic lupus erythematosus. Using genome-wide association and other genetic studies, her research team contributed to the identification of more than 30 genes linked to these disorders.

Dr. Criswells many honors include the Kenneth H. Fye, M.D., endowed chair in rheumatology and the Jean S. Engleman Distinguished Professorship in Rheumatology at UCSF, and the Henry Kunkel Young Investigator Award from the American College of Rheumatology. She also received UCSFs 2014 Resident Clinical and Translational Research Mentor of the Year. During her career, she has mentored some four dozen students (high school through medical/graduate school), medical residents, postdoctoral fellowsand junior faculty.

Dr. Criswell earned a bachelors degree in genetics and a masters degree in public health from the University of California, Berkeley; a D.Sc. in genetic epidemiology from the Netherlands Institute of Environmental Health Sciences, Rotterdam; and an M.D. from UCSF. In addition to completing a residency in internal medicine and a fellowship in rheumatology, she is certified as a first responder in wilderness medicine.

The mission of the NIAMS, a part of the U.S. Department of Health and Human Services' National Institutes of Health (NIH), is to support research into the causes, treatment and prevention of arthritis and musculoskeletal and skin diseases; the training of basic and clinical scientists to carry out this research; and the dissemination of information on research progress in these diseases. For more information about the NIAMS, call the information clearinghouse at (301) 495-4484 or (877) 22-NIAMS (free call) or visit the NIAMS website at https://niams.nih.gov.

About the National Institutes of Health (NIH):NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit http://www.nih.gov.

NIHTurning Discovery Into Health


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NIH taps Dr. Lindsey Criswell as director of the National Institute of Arthritis and Musculoskeletal and Skin Diseases - National Institutes of Health

A versatile genetic control system in mammalian cells and mice responsive to clinically licensed sodium ferulate – Science Advances

Dynamically adjustable gene- and cell-based therapies are recognized as next-generation medicine. However, the translation of precision therapies into clinics is limited by lack of specific switches controlled by inducers that are safe and ready for clinical use. Ferulic acid (FA) is a phytochemical with a wide range of therapeutic effects, and its salt sodium ferulate (SF) is used as an antithrombotic drug in clinics. Here, we describe an FA/SF-adjustable transcriptional switch controlled by the clinically licensed drug SF. We demonstrated that SF-responsive switches can be engineered to control CRISPR-Cas9 systems for on-command genome/epigenome engineering. In addition, we integrated FA-controlled switches into programmable biocomputers to process logic operations. We further demonstrated the dose-dependent SF-inducible transgene expression in mice by oral administration of SF tablets. Engineered switches responsive to small-molecule clinically licensed drugs to achieve adjustable transgene expression profiles provide new opportunities for dynamic interventions in gene- and cell-based precision medicine.

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A versatile genetic control system in mammalian cells and mice responsive to clinically licensed sodium ferulate - Science Advances

Spark Therapeutics Deepens Drug Development Expertise in Hematology and Rare Disease with Appointment of Gallia G. Levy, MD, Ph.D., as Chief Medical…

PHILADELPHIA, Aug. 10, 2020 (GLOBE NEWSWIRE) -- Spark Therapeutics, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY) and a fully integrated, commercial gene therapy company dedicated to challenging the inevitability of genetic disease, today announced the appointment of Gallia Levy, M.D., Ph.D., as chief medical officer. Dr. Levy will be responsible for strategic and operational leadership across all functions in the product development lifecycle, including setting the global development strategy for current and future pipeline programs.

We are thrilled to welcome Dr. Gallia Levy to our growing gene therapy company striving to create a world where no life is limited by genetic disease, said Jeffrey D. Marrazzo, chief executive officer, Spark Therapeutics. Dr. Levys passion for hematology and gene therapy research is immediately evident and exactly the perspective needed to achieve our goal of unlocking the full potential of gene therapy. Especially during this pivotal time in hemophilia research, Dr. Levys deep understanding of rare blood disorders and the community will help accelerate our ability to deliver potentially transformative gene therapies for hemophilia, while progressing potential gene therapies for other genetic disease across our pipeline.

Dr. Levy joins Spark Therapeutics from Genentech, also a member of the Roche Group, where she served as the Vice President and Global Head of the Rare Blood Disorders franchise in Product Development. In this role, she was responsible for the clinical development of HEMLIBRA for hemophilia A as well as treatments for other rare blood disorders such as paroxysmal nocturnal hemoglobinuria (PNH) and atypical hemolytic uremic syndrome (aHUS). She played a key role in the evolution of gene therapy as a new modality within the Roche Group.

Ive spent my career working to find new, innovative treatment approaches for patients affected by rare, life-altering disorders, and it is with great pride that I join the Spark team to help advance novel gene therapy programs and create next-generation solutions for patients, said Dr. Levy. Spark Therapeutics shares the same affinity for breaking barriers and putting the patient first, and I look forward to what we will achieve together.

Dr. Levy first joined Genentech in 2009, where she worked in both early and late-stage clinical development. She later moved to Portola Pharmaceuticals, where she led the clinical development program for hematology and oncology indications and returned to Genentech in 2014 to lead the hemophilia program.

Dr. Levy is board-certified in hematology and holds an M.D. and Ph.D. in Molecular and Cellular Biology from the University of Michigan. She completed her residency in internal medicine at Stanford University and a fellowship in hematology and oncology at the University of California, San Francisco. She also holds an M.S. in of Molecular and Cellular Biology from the University of Paris, VI and a B.A. from the University of California, Berkeley.

About Spark Therapeutics AtSpark Therapeutics, a fully integrated, commercial company committed to discovering, developing and delivering gene therapies, we challengethe inevitability of genetic diseases,includingblindness, hemophilia, lysosomal storage disorders and neurodegenerative diseases.We currently have four programs in clinical trials.At Spark, a member of the Roche Group, we see the path to a world where no life is limited by genetic disease. For more information, visit http://www.sparktx.com, and follow us on Twitter and LinkedIn.

Media Contact:Kevin Giordanokevin.giordano@sparktx.com(215) 294-9942

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Spark Therapeutics Deepens Drug Development Expertise in Hematology and Rare Disease with Appointment of Gallia G. Levy, MD, Ph.D., as Chief Medical...

Chromosomal Rearrangements Associated with Chemotherapeutic Drug Resistance | McDonnell Boehnen Hulbert & Berghoff LLP – JD Supra

Chemotherapeutic drug resistance is one reason cancer remains an unsolved clinical problem despite the efforts ever since President Nixon declared his "War on Cancer" in 1971. Cancer cells, due in part to the genetic destabilization characteristic of the disease, are capable of expressing genes (normal or aberrant) that permit the cell to avoid the cytotoxic effect of such drugs with the patient providing the situs of selection for and growth of resistant cells. The phenomenon is certain tumor types can have more deleterious consequences than in others, and this is particularly true for glioblastomas (and their non-malignant counterparts, gliomas), cancer of the cells that protect neurons in brain. That organ, confined to the skull, cannot accommodate tumor growth without damaging the brain with which it is confined.

The chemotherapeutic drug of choice for treating glioblastomas is temezolomide (TMZ), an oral alkylating agent that had its chemotherapeutic effect by introducing alkyl groups onto nucleotide bases (preferably at the N-7 and O-6 positions of guanine and N-3 position of adenine) in tumor cell DNA preferentially (due to the greater amount of DNA synthesis occurring in these cells) and disrupting the process leading to cell death (the O-6 methylation having the greatest capacity to induce apoptosis or programmed cell death).O-6-methylguanosnine DNA methyltransferase (MGMT) is the cellular enzyme responsible for repairing alkylated bases in DNA and reduced expression of this gene (e.g., by hypermethylation of the MGMT promoter) is a biomarker for TMZ sensitivity in gliomas and glioblastomas. Recently, a multinational team of researchers* reported genetic rearrangements associated with TMZ resistance, in a paper entitled "MGMT genomic rearrangements contribute to chemotherapy resistance in gliomas" published in Nature Communications. This paper shows a subset of gliomas with rearrangements in the MGMT gene that produce overexpression of the gene and resistance as a result. These authors screened 252 TMZ-treated recurrent gliomas by RNA sequencing and found eight different MGMT genetic fusions (designated BTRC-MGMT,CAPZB-MGMT,GLRX3-MGMT,NFYC-MGMT,RPH3A-MGMT, andSAR1A-MGMTin high-grade gliomas, HGG, andCTBP2-MGMTandFAM175B-MGMT in low-grade gliomas, LGG, in the paper) in seven patients (6 females) with recurrent disease, created by chromosomal rearrangement (see Figure 1c from paper; shown below). These individuals' tumors showed "significantly higher" expression of the rearranged MGMT gene product.

Upon further study, the authors report that five of the eight rearranged genes were located on Chromosome 10 in the vicinity of the MGMT gene itself. The breakpoint in the MGMT was uniformly found at the boundary of exon 2 of the MGMT gene, at a point 12 basepairs upstream of the ATG translation "start" codon. In three of the rearrangements, the breakpoint in the partner gene in the genetic fusion was found in the 5' untranslated region (UTR). All fusions were found to be in-frame (i.e., the reading frame of the MGMT transcript was not disrupted) and the functional regions of the MGMT protein (the methyltransferase domain and DNA-binding domain) were intact. A more fine-structure mapping experiment in the genetic rearrangement resulting in FAM175B-MGMTfound that the fusion was the consequence of a deletion of 4.8 Mb.

The effect of these rearrangements on MGMT expression was elucidated using CRIPSR-Cas9 to produce the BTRC-MGMT, NFYC-MGMT, SAR1A-MGMT, and CTBP2-MGMT rearrangements in cells of two glioblastoma cell lines, U251 and U87. When these cells and their untreated counterparts were challenged by growth in vitro with TMZ, only cells bearing the rearrangements (as confirmed by PCR analysis) were shown to be TMZ resistant. Unlike genetic rearrangements in other cancers that produce fusion proteins (such as the abl-bcr gene produced in chronic myelogenous leukemia bearing the diagnostic Philadelphia chromosome), because most of the rearrangements found involving the MGMT gene were located upstream of the initiation codon of the MGMT gene these authors reasoned that these rearrangements produce increased expression of MGMT leading to TMZ resistance because the cells were better able to repair the methylation injury and replicate functionally. This hypothesis was supported by real-time quantitative PCR analysis of MGMT transcripts in cells bearing the rearrangements, that showed a "striking" increase in expression of MGMT-encoding transcripts (an observation also found in tumors from patients whose gliomas or glioblastomas showed these rearrangements), and Western blot analysis confirmed higher expression levels of the MGMT protein. In two of the rearrangements (BTRC-MGMT and NFYC-MGMT), higher molecular weight fusion proteins were detected as predicted from the genetic data. These results were also replicated in patient tumor-derived stem cells for the BTRC-MGMTandSAR1A-MGMT rearrangements.

These results, and the researchers' conclusion that these rearrangements caused TMZ resistance by overexpression of MGMT, were confirmed by re-establishing TMZ sensitivity in these cells in the presence of O6-benzylguanine (O6-BG), an MGMT inhibitor. These results were further confirmed by detection of double-strand breaks in DNA in these cells in the presence of TMZ and O6-BG.

The relevance of these results to TMZ resistance in vivo was demonstrated using nude mouse xenograft models bearing tumors produced using BTRC-MGMT U251 cells and U251 cells without the rearrangement as control; these cells also contained a recombinant luciferase gene. Mice containing the rearrangement showed no significant prolongation of lifespan in the presence or absence of TMZ, indicating tumor cell resistance, whereas TMZ treatment of nave U251 cells showed improved survival.

While hypomethylation of the native MGMT promoter is the most frequently change associated with TMZ resistance, the results presented in this paper illustrate an alternative mechanism for glioblastomas and gliomas to acquire resistance to TMZ, the only current chemotherapeutic drugs for these maladies. Because these rearrangements were found in patients with recurrent tumors, these authors hypothesize that the rearrangements were selected or by TMZ treatment. A similar rearrangement has also been found in another cancer, medulloblastoma, after TMZ relapse. These authors also suggest that detection of these rearrangements can be used clinically to determine appropriate treatment modalities, particularly for recurrent disease.

* Seve Ballesteros Foundation Brain Tumor Group, Molecular Oncology Programme, Spanish National Cancer Research Center; Division of Life Science, Department of Chemical and Biological Engineering, Center of Systems Biology and Human Health and State Key Laboratory of Molecular Neuroscience, The Hong Kong University of Science and Technology; Beijing Neurosurgical Institute, Capital Medical University; Department of Neurosurgery, Samsung Medical Center, Sungkyunkwan University School of Medicine; Department of Systems Biology, Columbia University; The Jackson Laboratory for Genomic Medicine; and Molecular Cytogenetics Group, Human Cancer Genetics Program, Spanish National Cancer Research Center, CNIO, 28029, Madrid, Spain

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Chromosomal Rearrangements Associated with Chemotherapeutic Drug Resistance | McDonnell Boehnen Hulbert & Berghoff LLP - JD Supra

Jae Jung, Ph.D., Appointed as Chair of Cleveland Clinic Lerner Research Institute’s Department of Cancer Biology – Health Essentials from Cleveland…

Jae Jung, Ph.D.

Cleveland Clinic has appointed Jae Jung, Ph.D., chair of Lerner Research Institutes Department of Cancer Biology. Jung will also serve as director of the new Center for Global and Emerging Pathogens Research, which will focus on public health threats ranging from the Zika virus to SARS-CoV-2 (which causes COVID-19).

Jung is an internationally renowned expert in virology and virus-induced cancers who has broken ground in the field of inflammation, immune-oncology and emerging pathogens.

As chair of Cancer Biology, he will lead the departments work in understanding the biological underpinnings of cancer ranging from genetic and molecular pathways to disease manifestation. The department is home to leaders in the field of several cancer research areas including prostate cancer, glioblastoma and stem cells. He will closely collaborate with cancer researchers across Northeast Ohio and Cleveland Clinic, including the new Center for Immunotherapy and Precision Immuno-Oncology.

Jungs cancer research focuses on virus-induced cancers, including Kaposis sarcoma, the most common tumor in patients with AIDS. For his work in this disease area, the National Cancer Institute awarded him the prestigious Outstanding Investigator Award in 2016.

Jung will also lead the Center for Global and Emerging Pathogens Research, which is focused on broadening understanding of emerging pathogens. The center spans Lerner Research Institute and the Cleveland Clinic Florida Research and Innovation Center in Port St. Lucie, Florida.

Jae Jung is a brilliant and global leader in research into the deep and complex intersections between the immune system and cancer, said Serpil Erzurum, M.D., chair of Lerner Research Institute. His work has defined how viruses induce cancers, which make up to 25% of cancers in the world. It is quite fortuitous at this time that we have recruited a world-class scientist in cancer and virus research, propelling our teams in Cleveland and Florida forward in both of these significant areas.

Jung has several research projects related to coronaviruses, including vaccine and drug development and has developed one of the first preclinical models to study SARS-CoV-2 infection and transmission to lead to development of a COVID-19 vaccine. His vaccine work utilizes nanoparticles that compel the coronavirus to use its own surface protein to produce antibodies that block viral infection. The hope is that this approach will have fewer side effects than other vaccines, especially among the older population that is particularly susceptible to COVID-19.

Jung and a multi-disciplinary team of scientists and clinicians in Ohio and Florida are collaborating to uncover the mechanisms of infectious agents and virus-induced cancers. He will lead virology, immunology and oncology researchers working to make laboratory discoveries about how pathogens spread and cause disease and will collaborate with Cleveland Clinics Center for Therapeutics Discovery. He recently received a $2.8 million grant from National Institutes of Health to develop a vaccine for a newly emerging tick-borne disease.

Jae Jung is a foremost authority in virus-related cancer and immunology who will build and grow our research programs to advance science and ultimately improve care for our patients, said Brian Bolwell, M.D., chairman of Taussig Cancer Institute and the Cleveland Clinic Cancer Center. He will bring together a team of experts to better understand the complexities of these cancers and emerging pathogens to develop critically needed treatments and vaccines.

I am excited to collaborate with Cleveland Clinics experts in immunotherapy, oncology and infectious disease to advance our knowledge of immunologic medicine, said Jung. Cleveland Clinics robust clinical and research infrastructure in Cleveland as well as at the new Florida Research and Innovation Center will enable us to develop innovative and novel approaches for new therapeutics and vaccines and make them available to people around the world.

Jung joins Cleveland Clinic from the University of Southern California, where he was chair of Molecular Microbiology and Immunology and director of the Institute of Emerging Pathogens and Immune Diseases. He earned his Ph.D. in microbiology from the University of California, Davis. He completed post-doctoral training and was later promoted to professor at Harvard Medical School. He is an elected fellow of the American Association for the Advancement of Science and the American Academy of Microbiology.

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Jae Jung, Ph.D., Appointed as Chair of Cleveland Clinic Lerner Research Institute's Department of Cancer Biology - Health Essentials from Cleveland...

Noel Rose, Who Demonstrated Autoimmunity Exists, Dies at 92 – The Scientist

Noel Rose, an immunologist and microbiologist whose early experiments underpinned the molecular mechanisms of autoimmune disease, died of a stroke July 30. He was 92.

As a young medical student, Rose worked alongside his mentor, Ernest Witebsky of the University at Buffalo, studying organ-specific antigens. The prevailing hypothesis for the last half century had been that the body was incapable of producing antigens against itself, an idea known as horror autotoxicus. Witebskys own academic lineage stretched back to the ideas original progenitor, Paul Ehrlich, who had coined the term in the 18th century.

But Rose showed that rabbits injected with their own thyroid-derived antigens mounted an immune response against the invading molecules that damaged or destroyed the animals thyroid. The body was indeed capable of attacking itself. The results were so outlandish that the first journals refused to publish the findings, and it took years of careful experimentation to finally topple the paradigm of horror autotoxicus.Over the next several decades, Rose would further characterize the genetic and environmental causes of autoimmune diseases, publishing more than 880 articles and book chapters on the subject, according to Johns Hopkins University.

In every aspect, [Rose] is the father of autoimmunity, George Tsokos, a professor of rheumatology at Harvard Medical School, told The Scientist in a profile of Rose this year. The man opened a whole chapter in the book of medicine.

Currently, there are more than 80 recognized autoimmune diseases, including lupus, type 1 diabetes, rheumatoid arthritis, and AIDS, that have sickened more than 20 million Americans. Speaking to The Washington Post in 1995, Rose called autoimmune diseases one of the big three, meaning cancer, heart disease, and autoimmune disease.

Rose was born December 3, 1927, in Stamford, Connecticut. His father, a physician who served during World War II, became a specialist in treating rheumatic fever, now considered to be an autoimmune disease, the Post reports.

Prior to his groundbreaking work, Rose frequently brushed up against the limitations of medical knowledge at the time. When he began his undergraduate degree at Yale University in the mid-1940s, he wanted to study microbiology, but he was only able to attend a handful of classes on the topic. Instead, he majored in zoology and took the electives in microbiology, which were taught by botanistsbacteria were largely thought to be plants at the time, The Scientist reported in June.

Rose decided to complete a PhD ahead of attending medical school. He joined the lab of microbiologist Harry Morton at the University of Pennsylvania in 1948, where he spent the next several years studying the flagella-like motor structures of Treponema pallidum, the bacterium that causes syphilis.

Next, Rose enrolled as a medical student at the University at Buffalo, where he would make many of his most important medical discoveries. It was here, working alongside Witebsky, that he first demonstrated autoimmunity in rabbits.

Rose extracted a protein called thyroglobulin from humans, horses, and pigs, treated it with a solution called Freunds adjuvant to induce an immune response, and injected it into rabbits. Even though the injected thyroglobulin was similar to the protein already in the rabbits body, the animals still produced protective antibodies. This was true even when the protein, primed by the adjuvant that induces an immune response, came from another rabbit, and most surprisingly, when the protein was extracted and re-injected into the same animal. When he looked at the thyroids of these rabbits, he found that they were often damaged, and sometimes destroyed, by the bodys own immune response.

After having their findings rejected during peer review, Witebsky and Rose turned to studying autoimmunity in humans, determined to replicate and refine their work. They focused on Hashimotos disease, a rare thyroid condition with no identifiable cause, showing that serum taken from patients developed the same type of antibodies when exposed to thyroglobulin that they had seen in rabbits. We went ahead and showed that this same destruction applies to humans and that you could induce a disease in an organ by immunizing it with a specific antigen of the same species, Rose had told The Scientist. And that was autoimmunity.

Having overturned the idea of horror autotoxicus, Rose says, the work came out of the walls, and he spent the next several decades furthering the study of autoimmune diseases. He graduated with his MD in 1964 and remained at the University at Buffalo. According to a memorial page by Johns Hopkins University, where his career would eventually take him, his lab at Buffalo was the first to show that the genes for the major histocompatibility complex, closely linked on human chromosome six, contain the primary genes that determine the risk for autoimmune diseases.

Rose moved his lab to Wayne State University in 1973, where he remained for almost a decade before finally accepting a position at Johns Hopkins in 1981 in the Bloomberg School of Public Health. There, Rose focused on environmental conditions that could trigger disease. In many diseases, Rose told The Scientist, genetics was always less than half the risk. We thought something from the environment must be involved.

His later work focused on myocarditis, an inflammation of the heart muscle, and Rose was still working up until his death. He found great promise in the advent of big data and using it to analyze hundreds or thousands and patients to identify the best possible treatments and preventives. What we want to do is avoid the train wreck from the beginning, and I think we can begin to do that, Rose told The Scientist. Thats what Im excited about.

Rose is survived by his wife of 69 years, Deborah, two sons, two daughters, 10 grandchildren, and five great-grandchildren.

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Noel Rose, Who Demonstrated Autoimmunity Exists, Dies at 92 - The Scientist

Invasion of the Body Snatchers: Viruses Can Steal Our Genetic Code to Create New Human-Virus Genes – SciTechDaily

Study unveils novel mechanism that allows viruses to produce unexpected proteins.

Like a scene out of Invasion of the Body Snatchers,a virus infects a host and converts it into a factory for making more copies of itself. Now researchers have shown that a large group of viruses, including the influenza viruses and other serious pathogens, steal genetic signals from their hosts to expand their own genomes.

This finding is presented in a study published online today and in print June 25 inCell.The cross-disciplinary collaborative study wasled byresearchers at the Global Health and Emerging Pathogens Institute at Icahn School of Medicine at Mount Sinai in New York, and at the MRC-University of Glasgow Centre for Virus Research in the UK.

The cross-disciplinary team of virologists looked at a large group of viruses known as segmented negative-strand RNA viruses (sNSVs), which include widespread and serious pathogens of humans, domesticated animals and plants, including the influenza viruses and Lassa virus (the cause of Lassa fever). They showed that, by stealing genetic signals from their hosts, viruses can produce a wealth of previously undetected proteins. The researchers labeled them as UFO (Upstream Frankenstein Open reading frame) proteins, as they are encoded by stitching together the host and viral sequences. There was no knowledge of the existence of these kinds of proteins prior to this study.

These UFO proteins can alter the course of viral infection and could be exploited for vaccine purposes.

The capacity of a pathogen to overcome host barriers and establish infection is based on the expression of pathogen-derived proteins, said Ivan Marazzi, PhD, Associate Professor of Microbiology at Icahn School of Medicine and corresponding author on the study. To understand how a pathogen antagonizes the host and establishes infection, we need to have a clear understanding of what proteins a pathogen encodes, how they function, and the manner in which they contribute to virulence.

Viruses cannot build their own proteins, so they need to feed suitable instructions to the machinery that builds proteins in their hosts cells. Viruses are known to do this through a process called cap-snatching, in which they cut the end from one of the cells own protein-encoding messages (a messenger RNA, or mRNA) and then extend that sequence with a copy of one of their own genes. This gives a hybrid message to be read.

For decades we thought that by the time the body encounters the signal to start translating that message into protein (a start codon) it is reading a message provided to it solely by the virus. Our work shows that the host sequence is not silent, said Dr. Marazzi.

The researchers show that, because they make hybrids of host mRNAs with their own genes, viruses (sNSVs) can produce messages with extra, host-derived start codons, a process they called start snatching. This makes it possible to translate previously unsuspected proteins from the hybrid host-virus sequences. They further show that these novel genes are expressed by influenza viruses and potentially a vast number of other viruses. The product of these hybrid genes can be visible to the immune system, and they can modulate virulence. Further studies are needed to understand this new class of proteins and what the implications are of their pervasive expression by many of the RNA viruses that cause epidemics and pandemics.

Ed Hutchinson, PhD, corresponding author and a research fellow at MRC-University of Glasgow Centre for Virus Research, said, Viruses take over their host at the molecular level, and this work identifies a new way in which some viruses can wring every last bit of potential out of the molecular machinery they are exploiting. While the work done here focusses on influenza viruses, it implies that a huge number of viral species can make previously unsuspected genes.

Researchers say the next part of their work is to understand the distinct roles the unsuspected genes play. Now we know they exist, we can study them and use the knowledge to help disease eradication, said Dr. Marazzi. A large global effort is required to stop viral epidemics and pandemics, and these new insights may lead to identifying novel ways to stop infection.

Read Viruses Can Steal Our Genetic Code to Create New Hybrid Human-Virus Genes to learn more about this research.

Reference: Hybrid Gene Origination Creates Human-VirusChimeric Proteins during Infection by Jessica Sook Yuin Ho, Matthew Angel, Yixuan Ma, Elizabeth Sloan, Guojun Wang, Carles Martinez-Romero, Marta Alenquer, Vladimir Roudko, Liliane Chung, Simin Zheng, Max Chang, Yesai Fstkchyan, Sara Clohisey, Adam M. Dinan, James Gibbs, Robert Gifford, Rong Shen, Quan Gu, Nerea Irigoyen, Laura Campisi, Cheng Huang, Nan Zhao, Joshua D. Jones, Ingeborg van Knippenberg, Zeyu Zhu, Natasha Moshkina, La Meyer, Justine Noel, Zuleyma Peralta, Veronica Rezelj, Robyn Kaake, Brad Rosenberg, Bo Wang, Jiajie Wei, Slobodan Paessler, Helen M. Wise, Jeffrey Johnson, Alessandro Vannini, Maria Joo Amorim, J. Kenneth Baillie, Emily R. Miraldi, Christopher Benner, Ian Brierley, Paul Digard, Marta uksza, Andrew E. Firth, Nevan Krogan, Benjamin D. Greenbaum, Megan K. MacLeod, Harm van Bakel, Adolfo Garca-Sastre, Jonathan W. Yewdell, Edward Hutchinson and Ivan Marazzi, 18 June 2020, Cell.DOI: 10.1016/j.cell.2020.05.035bioRxiv: 10.1101/597617v1

This study was supported by funders including the National Institute of Allergy and Infectious Diseases and the UK Medical Research Council.

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Invasion of the Body Snatchers: Viruses Can Steal Our Genetic Code to Create New Human-Virus Genes - SciTechDaily

The UK and TCELS to jointly support COVID-19 research in Thailand – GOV.UK

The UK Government, through the British Embassy Bangkok, and the Thailand Center of Excellence for Life Sciences (TCELS, under the Ministry of Higher Education, Science, Research and Innovation) have today agreed to share knowledge, technology, experience and business information, and to support the research in health and medicines.

TCELS CEO Dr. Nares Damrongchai signed a memorandum of understanding which states that the two organisations will give financial support to the Mahidol-Oxford Research Unit, Faculty of Tropical Medicine, Mahidol University, to conduct 2 research projects: i) the implementation of RT-LAMP technology and genome evolution analysis for 2019-nCov; and ii) the development of a spatiotemporal surveillance platform with interactive user interface for real-time evaluation of the COVID-19 epidemic situation in Thailand.

The expected outputs of the projects are RT-LAMP emergency test kit for COVID-19 which have been tested and ready for mass production, and the surveillance platform for COVID-19 transmission monitoring that fits for the current situation in Thailand. The platform will be used to evaluate the disease control policy in real time, building Thailands preparedness should there be a new wave of transmission. Both projects will be conducted by researchers from the Mahidol-Oxford Research Unit which is a collaboration between the UKs Oxford University and Thailands Mahidol University.

The MOU is the first one between the British Embassy Bangkok and TCELS which will lead to further collaborations on genomic studies. This is a significant step that builds on prior medical research collaborations that the UK and Thailand continue to have for many years with an aim to sustainably better the peoples livelihood and bring prosperity to both countries.

Brian Davidson, British Ambassador to Thailand, said:

The United Kingdom has been supporting middle-income countries through our Prosperity Fund Programmes to help them achieve sustainable and inclusive economic development. The Prosperity Funds Better Health Programme aims to improve the peoples health through partnership and collaborations with our partner countries. We are excited to be working with TCELS as a part of the global effort to fight against the pandemic that has disrupted the whole world. We hope the two research projects will help Thailand in its response to the coronavirus.

Dr. Nares Damrongchai, CEO of TCELS, said:

TCELS has the mission to support and groom Thailands research and innovation that entail health and medical products and services. We aim to build in Thailand the environment, infrastructure and human resources that will enable the international-standard health and medical innovations that are relevant. We also work with our network to ready our business and investment capacities to enter the medical hub industry. One of our approaches is to give financial support to health and medical research projects under TCELS. We would like to thank the UK Government and the British Embassy Bangkok for joining us in supporting important researches that respond to global challenges.

We will continue to work with the UK on the area of health and medical research. The next phase of our collaborations will be about developing the capacities of genetic counselors for medical genomics and precision medicines, for which we hope to be able to announce some good news in the near future.

Sarinplus Leelasaowapak (Jenny)Corporate Communications ManagerMobile : 097 123 9595e-mail: sarinplus@tcels.or.th

Songsang JatupornsathienCommunications ManagerMobile: 083 988 6766 e-mail: Songsang.Jatupornsathien@fco.gov.uk

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The UK and TCELS to jointly support COVID-19 research in Thailand - GOV.UK