Monthly Archives: June 2017

Hillsboro native Dr. Nancy J. Cox was honored this spring as the first recipient of the Richard M. Caprioli Research Award. Dr. Cox is currently the director of the Vanderbilt Genetics Institute in Nashville, TN.

The daughter of the late Gene and Helen Cox, she is a 1974 graduate of Hillsboro High School and was selected as the second Hillsboro Education Foundation Distinguished Alumni Award recipient in 2002.

Dr. Cox earned her bachelor of science degree in biology from the University of Notre Dame in 1978 and her doctorate in human genetics from Yale University in 1982.

She completed a postdoctoral fellowship in genetic epidemiology at Washington University and was a research associate in human genetics at the University of Pennsylvania.

In 1987, she was hired at the University of Chicago. She was appointed full professor in the departments of medicine and human genetics in 2004 and chief of the section of genetic medicine the following year.

In 2012, she was named a University of Chicago Pritzker Scholar. In 2015, Dr. Cox was hired at Vanderbilt University School of Medicine as the Mary Phillips Edmonds Gray Professor of Genetics, founding director of the Vanderbilt Genetics Institute and director of the Division of Genetic Medicine in the Department of Medicine. She is a fellow of the American Association for the Advancement of Science

Throughout her career as a quantitative geneticist, Dr. Cox has sought to identify and characterize the genetic component to common human diseases and clinical phenotypes like pharmacogenomics traits (how genes affect drug response).

Her work has advanced methods for analyzing genetic and genomic data from a wide range of complex traits and diseases, including breast cancer, diabetes, autism, schizophrenia, bipolar disorder, Tourette syndrome, obsessive-compulsive disorder, stuttering and speech and language impairment.

Through the national Genotype Tissue Expression (GTEx) project, Dr. Cox also contributed to the development of genome predictors of the expression of genes, and she also has investigated the genetics of cardiometabolic phenotypes such as lipids, diabetes and cardiovascular disease.

With colleagues at the University of Michigan, Dr. Cox is generating content for the Accelerating Medicine Partnership between the National Institutes of Health (NIH), U.S. Food and Drug Administration, biopharmaceutical companies and non-profit organizations. The goal of the partnership is to identify and validate promising biological targets, increase the number of new diagnostics and therapies for patients, and reduce the cost and time it takes to develop them.

Dr. Cox is co-principal investigator of an analytic center within the Centers for Common Disease Genomics, another NIH initiative that is using genome sequencing to explore the genomic contributions to common diseases such as heart disease, diabetes, stroke and autism. A major resource for the Cox lab is Vanderbilts massive biobank, BioVU, which contains DNA samples from more than 230,000 individuals that are linked to de-identified electronic health records.

Dr. Cox is the author or co-author of more than 300 peer-reviewed scientific articles. She is former editor-in-chief of the journal Genetic Epidemiology, and is the current president of the American Society of Human Genetics.

For developing new methods that have aided researchers worldwide in identifying and characterizing of the genetic and genomic underpinnings of diseases and complex traits, Dr. Cox is the first recipient of the inaugural Richard M. Caprioli Research Award.

Dr. Cox and her husband, Dr. Paul Epstein live in Nashville, TN, and have two grown daughters, Bonnie Epstein and Carrie Epstein.

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Hillsboro Native Earns Honors At Vanderbilt - thejournal-news.net

June 1, 2017 This microscopic image of fibroblast cells shows the induction of cell fusion by a newly described gene and its protein, called myomerger. Multi-nucleus cells expressing genes needed to form skeletal muscle can be seen in flower-like clumps forming as cells fuse together. Reporting results in Nature Communications, the researchers seek ways to develop regenerative therapies for muscle disorders by getting stem cells to fuse and form functioning skeletal muscle tissues. Credit: Cincinnati Children's

A detour on the road to regenerative medicine for people with muscular disorders is figuring out how to coax muscle stem cells to fuse together and form functioning skeletal muscle tissues. A study published June 1 by Nature Communications reports scientists identify a new gene essential to this process, shedding new light on possible new therapeutic strategies.

Led by researchers at the Cincinnati Children's Hospital Medical Center Heart Institute, the study demonstrates the gene Gm7325 and its protein - which the scientists named "myomerger" - prompt muscle stem cells to fuse and develop skeletal muscles the body needs to move and survive. They also show that myomerger works with another gene, Tmem8c, and its associated protein "myomaker" to fuse cells that normally would not.

In laboratory tests on embryonic mice engineered to not express myomerger in skeletal muscle, the animals did not develop enough muscle fiber to live.

"These findings stimulate new avenues for cell therapy approaches for regenerative medicine," said Douglas Millay, PhD, study senior investigator and a scientist in the Division of Molecular Cardiovascular Biology at Cincinnati Children's. "This includes the potential for cells expressing myomaker and myomerger to be loaded with therapeutic material and then fused to diseased tissue. An example would be muscular dystrophy, which is a devastating genetic muscle disease. The fusion technology possibly could be harnessed to provide muscle cells with a normal copy of the missing gene."

Bio-Pioneering in Reverse

One of the molecular mysteries hindering development of regenerative therapy for muscles is uncovering the precise genetic and molecular processes that cause skeletal muscle stem cells (called myoblasts) to fuse and form the striated muscle fibers that allow movement. Millay and his colleagues are identifying, deconstructing and analyzing these processes to search for new therapeutic clues.

Genetic degenerative disorders of the muscle number in the dozens, but are rare in the overall population, according to the National Institutes of Health. The major categories of these devastating wasting diseases include: muscular dystrophy, congenital myopathy and metabolic myopathy. Muscular dystrophies are a group of more than 30 genetic diseases characterized by progressive weakness and degeneration of the skeletal muscles that control movement. The most common form is Duchenne MD.

Molecular Sleuthing

A previous study authored by Millay in 2014 identified myomaker and its gene through bioinformatic analysis. Myomaker is also required for myoblast stem cells to fuse. However, it was clear from that work that myomaker did not work alone and needed a partner to drive the fusion process. The current study indicates that myomerger is the missing link for fusion, and that both genes are absolutely required for fusion to occur, according to the researchers.

To find additional genes that regulate fusion, Millay's team screened for those activated by expression of a protein called MyoD, which is the primary initiator of the all the genes that make muscle. The team focused on the top 100 genes induced by MyoD (including GM7325/myomerger) and designed a screen to test the factors that could function within and across cell membranes. They also looked for genes not previously studied for having a role in fusing muscle stem cells. These analyses eventually pointed to a previously uncharacterized gene listed in the database - Gm7325.

Researchers then tested cell cultures and mouse models by using a gene editing process called CRISPR-Cas9 to demonstrate how the presence or absence of myomaker and myomerger - both individually and in unison - affect cell fusion and muscle formation. These tests indicate that myomerger-deficient muscle cells called myocytes differentiate and form the contractile unit of muscle (sarcomeres), but they do not join together to form fully functioning muscle tissue.

Looking Ahead

The researchers are building on their current findings, which they say establishes a system for reconstituting cell fusion in mammalian cells, a feat not yet achieved by biomedical science.

For example, beyond the cell fusion effects of myomaker and myomerger, it isn't known how myomaker or myomerger induce cell membrane fusion. Knowing these details would be crucial to developing potential therapeutic strategies in the future, according to Millay. This study identifies myomerger as a fundmentally required protein for muscle development using cell culture and laboratory mouse models.

The authors emphasize that extensive additional research will be required to determine if these results can be translated to a clinical setting.

Explore further: Researchers turn stem cells into somites, precursors to skeletal muscle, cartilage and bone

More information: Nature Communications (2017). DOI: 10.1038/NCOMMS15665

Adding just the right mixture of signaling moleculesproteins involved in developmentto human stem cells can coax them to resemble somites, which are groups of cells that give rise to skeletal muscles, bones, and cartilage ...

A team led by Jean-Franois Ct, researcher at the IRCM, identified a ''conductor'' in the development of muscle tissue. The discovery, published online yesterday by the scientific journal Proceedings of the National ...

Athletes, the elderly and those with degenerative muscle disease would all benefit from accelerated muscle repair. When skeletal muscles, those connected to the bone, are injured, muscle stem cells wake up from a dormant ...

Johns Hopkins researchers report they have inadvertently found a way to make human muscle cells bearing genetic mutations from people with Duchenne muscular dystrophy (DMD).

Duchenne muscular dystrophy is a chronic disease causing severe muscle degeneration that is ultimately fatal. As the disease progresses, muscle precursor cells lose the ability to create new musclar tissue, leading to faster ...

Researchers at Sanford Burnham Prebys Medical Research Institute (SBP) have conclusively identified the protein complex that controls the genes needed to repair skeletal muscle. The discovery clears up deep-rooted conflicting ...

A University of California, Berkeley, study of mice reveals, for the first time, how puberty hormones might impede some aspects of flexible youthful learning.

The bacteria in a child's gut appears to be influenced as early as its first year by ethnicity and breastfeeding, according to a new study from McMaster University.

The human body runs according to a roughly 24-hour cycle, controlled by a "master" clock in the brain and peripheral clocks in other parts of the body that are synchronized according to external cues, including light. Now, ...

A detour on the road to regenerative medicine for people with muscular disorders is figuring out how to coax muscle stem cells to fuse together and form functioning skeletal muscle tissues. A study published June 1 by Nature ...

Cholesterol, a naturally occurring compound at the lung surface, has been shown to have a clear effect on the properties of this nanoscale film that covers the inside of our lungs. Cholesterol levels in this system may affect ...

Researchers from Monash University have developed a new drug delivery strategy able to block pain within the nerve cells, in what could be a major development of an immediate and long lasting treatment for pain.

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Link:
One gene closer to regenerative therapy for muscular disorders - Medical Xpress

Paul Cerrato says he first started researching precision medicine almost 30 years ago.

"Back then it wasn't called precision medicine, but when I was in graduate school I did my final master's thesis on 'biochemical individuality' that was the buzzword," said Cerrato, a healthcare journalist. "That was the beginnings of the thinking about personalizing care: trying to understand how each human body is different before they can figure out how to treat individuals."

Fast forward three decades and the excitement around precision medicine seems to finallybe at a tipping point thanks to maturing technology, more cost-effective gene sequencing and momentum-building federal projects such as the Precision Medicine Initiative and the Cancer Moonshot.

[Also:How Penn Medicine primed its IT infrastructure for precision medicine]

But the obstacles are also substantial from the high cost of drugs for precision oncology, lack of widespread interoperability, skepticism on the part of some clinicians and challenges related to patient engagement.

At the Healthcare IT News Precision Medicine Summit in Boston on June 12, Cerrato, along with Beth Israel Deaconess Medical Center CIO John Halamka, MD, will discuss the obstacles and opportunities facing personalized medicine.

Halamka knows well about the opportunities. And not just because he's a renowned expert on health information technology. His wife, Kathy, was successfully treated for breast cancer with help from some sophisticated precision medicine tools and techniques.

Cerrato and Halamka just finished a book together, Realizing the Promise of Precision Medicine, due to be published by Elsevier in October. In it, they offer some insights into Kathy's treatment, but focus more generally on the transformative potential of personalized care, exploring the role of electronic health records, patient-facing mobile apps, health information exchange and more.

They're hopeful about the future. But cognizant that some substantial hurdles will need to be overcome along the way.

"When we were researching the book there was a lot of positive data, but also quite a bit of skepticism, and criticism of the whole concept that precision medicine should have such an important role in patient care," said Cerrato.

One of the central goals of their book, and their talk in Boston this month, is to counter the misapprehension of many clinicians that precision medicine has limited applications in the real-world care settings.

For instance, he said, many physicians argue: "'Personalized medicine? We already do that. We don't need to spend another $200 or $300 million on a precision medicine initiative because we already provide personalized care on a daily basis.'

"Of course, the answer to that is, that's personalized care with a lower-case P," said Cerrato. "We're talking about something much more sophisticated and much more involved: genomics and microbiome and lots of other risk factors. The average doc might be personalizing medicine by switching from one antibiotic to another, or asking patients if they have liver disease before they decide to use a statin, or those kinds of things. That's personalization, but those are the baby steps."

Another objection has less to do with changing culture and mindset and more to do with financial realities, he said. And this one in the near term, at least has some merit.

"The second obstacle we're dealing with is the objection of some thought leaders in clinical medicine that precision medicine will simply cost too much," said Cerrato. "There's some substance to that objection. You look at the cost of precision medicine drugs that have been coming out the past couple years they're really astronomical. And the return on investment, very often, is limited, especially in cancer care," where hugely expensive drugs are sometimes only able to prolong life for a few months or a year.

"It's a work in progress," he said. "We don't have a simple answer to that. But we've got to put it out there. One of the reasons we want to give a presentation like this and write a book like this is we want to convince docs in the trenches, and thought leaders in clinical care, that precision medicine really is a model they should be following. In order to do that, we really should be up front about their criticisms. We have to address them directly."

Another common concern is that "physicians' workloads would be greatly increased if they had to start practicing precision medicine on a daily basis," said Cerrato. "You're talking about mountains and mountains of information. How do you translate that so a physician who only has 15 minutes with a patient can use that in daily care?"

Again, not an unreasonable point to make. Gene sequencing is still pretty expensive, too. But even if it cost a dollar, the average primary care physician does not know how to interpret genomic data."

Technology also poses big challenges, especially while interoperability remains elusive. "Without interoperability, precision medicine is really not going to get too far."

EHRs too are lagging badly in their ability to handle data-intensive genomics. "Right now we're not at the stage where a physician can just open up his electronic health record and say 'OK, what does this patient's gene sequencing look like?' We're not there yet."

But there are big reasons for optimism, too. As Halamka said, Kathy's treatment benefited greatly from technologies such as Clinical Query 2, software at Beth Israel Deaconess that allows physicians to see anonymized health records of cohorts of patients, tailored by different demographic and clinical parameters.

"It looks at all the patients who have had similar signs and symptoms and lab values and shows what were the treatment recommendations for those patients," said Cerrato. "It allowed the oncology team to individualize the care for Kathy so it would meet her needs, while eliminating the possibility of her getting treated with a protocol that would do more harm than good."

Most precision medicine and genomics work is still being done at advanced academic medical centers such as BIDMC, of course.

But on a smaller scale, there's still big promise for other types of personalized treatments.

"There are certain aspects of the field that are already happening right now. Especially in the field of diabetes, there's enough out there in terms of mobile apps and other digital tools, that is allowing physicians who are interested to practice precision medicine today," said Cerrato.

"Scripps has come out with an app for asthmatics, and it does a lot of the heavy lifting for clinicians by allowing patents to put in some basic parameters about their peak flow readings and their medication use and a few other things," he added. "When a doc uses that for the asthmatic patient, they don't have to do all the work. The technology of the app will do it for them. It has built-in decision trees to help them make better decisions on a personalized basis."

The bottom line, said Cerrato, is that there are some aspects of precision medicine that are working for some docs now and there are some aspects that remain in the future either because they're not educated enough to know how to do it, or the clinical data is not there yet."

How long it takes for genomics and personalized treatments to become commonplace still depends on the answers to a host of clinical, financial, technological and cultural questions, he said, but "I do think it will be the standard of care in the future."

Twitter:@MikeMiliardHITN Email the writer: mike.miliard@himssmedia.com

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Promise of precision medicine depends on overcoming big obstacles - Healthcare IT News

In Brief The CRISPR process will be used inside the human body for the first time on July 15th to combat HPV, which impacts millions of people worldwide. And this is just one of a huge amount of proposed CRISPR studies occurring soon. Uninvasive CRISPR

A new CRISPR trial, which hopes to eliminate thehuman papillomavirus (HPV), is set to be the first to attempt to use thetechnique inside the human body. In the non-invasive treatment, scientists will apply a gel that carries the necessary DNA coding for the CRISPR machinery to the cervixes of 60 women between the ages of 18 and 50. The team aims to disable the tumor growth mechanism in HPV cells.

The trial stands in contradistinction to the usual CRISPR method of extracting cells and re-injecting them into the affected area; although it will still use the Cas9 enzyme (which acts as a pair of molecular scissors) and guiding RNA that is typical of the process.

20 trials are set to begin in the rest of 2017 and early 2018. Most of the research will occur in China, and will focus on disabling cancers PD-1 gene that fools the human immune system into not attacking the cells. Different trials are focusing on different types of cancer including breast, bladder, esophageal, kidney, and prostate cancers.

The study, if it succeeds, will be promising for sufferers of HPV and act as a milestone in the CRISPR process. Although HPV is not necessarily cancerous, it cancause cervical cancer. In the U.S. alone, there are more than 3 million new infections every year.Although there is a vaccine for the virus, currently, once you have it you can never get rid of it.

More generally, the CRISPR process could be nothing short of a miracle: if it passes all medical tests it wouldnt just make medicine a whole new kettle of fish, it would reinvent the kettleand the fish, for almost any field. It is cheaper than other gene editing therapies, and could potentially save millions of lives by curing diseases we can only deal with therapeutically like cancer, diabetes and cystic-fibrosis. Crops could be altered more effectively using the process. Drugs and materials that were never possible before could be pioneered.

However, it is still extremely nascent technology, and many fear that there could also be a host of unexpected consequences. Recently, it has been found that it causes hundreds of unexpected mutations in DNA. While these concerns are valid, more research is necessary. Which is why the upcoming studies over the next few years are so vital to the future of our health.

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A World First CRISPR Trial Will Edit Genes Inside the Human Body - Futurism

What happened

Shares of gene editing pioneer Editas Medicine (NASDAQ:EDIT) dropped nearly 16% today after a new study published in Nature Methods drew attention to unintended effects of using the highly touted genetic engineering tool known as CRISPR. Shares of genome-editing peers CRISPR Therapeutics (NASDAQ:CRSP) and Intellia Therapeutics (NASDAQ:NTLA) were down as much as 6.9% and 14.9%, respectively, on the news.

The study, conducted by a team from Columbia University Medical Center, provided data showing that the technology can "introduce hundreds of unintended mutations into the genome," according to Genetic Engineering & Biotechnology News. That contradicts one of the better-known characteristics of CRISPR: precision.

Simply put, it's not sitting well with investors, who are (in knee-jerk fashion) adjusting the value placed on early-stage platforms, especially Editas Medicine, which will be the first of the group to enter clinical trials. As of 3:31 p.m. EDT, the stock had settled to a 11.3% loss.

Image source: Getty Images.

The study is among the first to quantify the specificity of CRISPR tools, which work by delivering gene editing enzymes to specific parts of the genome through the use of synthetic guide RNAs. Or that's how they're supposed to work. The authors of the study show that although intended edits can be made with respectable efficiency, such as correcting a mutation in a gene that causes blindness in mice, there are also unintended secondary edits made to the genome.

This may seem like a bombshell report, but it's a matter of optics. Researchers have never shied away from the reality that CRISPR gene editing tools can stray off target and make unintended edits to genomes in mammalian cells (i.e., humans). Many labs -- including Editas Medicine, CRISPR Therapeutics, and Intellia Therapeutics -- are working on increasing the efficiency and specificity of the technology. This is how science works. By quantifying these off-target mutations, which the paper attempted to do, researchers can begin to better understand how to improve the technology.

Investors and traders did not take the same cool-headed approach to the news, instead giving into a knee-jerk reaction to adjust the value of each pre-clinical technology platform. While off-target edits could prove troublesome for a CRISPR therapeutic used in humans, it's important to remember that there are currently no clinical trials underway in the United States. Editas Medicine will become the first to initiate a clinical trial later this year.

The sharp contrasts in reactions from researchers and investors is likely driven by how CRISPR is perceived by the media. Unfortunately, there is a generous amount of hyped-up science journalism that sticks to simple narratives -- "CRISPR has arrived and will cure all diseases!" -- instead of more nuanced takes that give equal weight to each current obstacles and future potential facing an emerging technology. Just remember: Biology is never quite so simple.

The results from the study don't really change anything, except for bringing more attention to the already existent clinical risk inherent to the development of early-stage CRISPR therapeutics. There is still plenty of work and new technology left to be developed before gene editing fulfills its promise in treating and curing human diseases. Hopefully, this can be a long-term positive for investors in CRISPR stocks by forcing them to listen to the fundamental hurdles for the technology. Hopefully.

Maxx Chatsko has no position in any stocks mentioned. The Motley Fool has no position in any of the stocks mentioned. The Motley Fool has a disclosure policy.

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Here's Why Editas Medicine Fell as Much as 15.7% Today - Motley Fool