The Jackson Laboratory for Genomic Medicine

Event Spotlight: Global Genomics Conference

Genomics and Society: expanding the ELSI universe


UConn Health and The Jackson Laboratory Host Global Genomics Conference

Good genomics research requires healthy curiosity, powerful data analysis, rigorous scientific methodology — and a strong ethical grounding. UConn Health and the Jackson Laboratory for Genomic Medicine co-hosted the Ethical, Legal, and Social Implications Research Program’s (ELSI) fourth-annual conference June 5 through 7 to explore how ethical decisions surrounding genomic discoveries are informed by the legal and social context of our society.

Nearly 300 people attended the three-day “Genomics and Society: Expanding the ELSI Universe” conference, which brought experts from around the world to UConn Health in Farmington, Connecticut, to discuss both what we can do with our genomic knowledge and the responsibilities that come with that power.

“The increase in genomic testing and technology are fueling breakthrough discoveries here in Connecticut and around the globe for heart disease, cancer, and a host of rare diseases,” said Dr. Bruce T. Liang, dean of UConn School of Medicine. “However, these promising personalized medicine therapies and our greater genetic knowledge may also come with a steep societal price if we don’t address the associated concerns in a timely fashion.”

Keynote speakers from the National Institutes of Health (NIH) and universities across the country spoke about the ethics of genomics in the clinical setting; the relationship between genes, ancestry, and identity; and the NIH’s All of Us initiative. All of Us seeks to broaden the genetic database used for research in the United States so that it more accurately reflects the citizenry and the differences in lifestyle, environment, and biology encountered in different populations across the country.

Much of the funding for ELSI comes from the National Human Genome Research Institute, with the goal of supporting research that anticipates and addresses the societal impact of genomic science. The institute has four broad priorities: genomic research; tracking how that research influences health care; exploring how social norms and beliefs affect how we understand genetic advances and how we use them; and legal, regulatory, and public policy issues. Workshops at the conference covered specific topics from those areas, including the implications of genetic testing in the criminal justice system; the uses and misuses of the gene editing technique known as CRISPR; and the controversies over the appropriate use of genetics in psychiatric, neurologic, and behavioral fields.

More information about the ELSI project.

Tell-Tale Heart

‘Heart-In-A-Dish’ Sheds Light on Heart Disease Genetics

By Nicole Davis for The Jackson Laboratory for Genomic Medicine
Photography by Peter Morenus

Dr. Travis Hinson holds petri dishes containing beating heart tissue

Dr. J. Travis Hinson is seen holding petri dishes that contain heart cells. Hinson, a joint faculty appointment at UConn Health and The Jackson Laboratory for Genomic Medicine, has pioneered a system to study the genetics of heart failure by recreating beating heart tissue using patients’ stem cells. Photo: Peter Morenus


When a patient shows symptoms of cancer, a biopsy is taken. Scientists study the tissue, examining it under a microscope to determine exactly what’s going on.

But the same can’t be done for heart disease, the leading cause of death among Americans. Until now.

Dr. J. Travis Hinson, a physician-scientist who joined the faculties of UConn Health and The Jackson Laboratory for Genomic Medicine (JAX) in January, uses a novel system he pioneered to study heart tissue.

Hinson engineers heart-like structures with cells containing specific genetic mutations in order to study the genetics of cardiomyopathies, the diseases of the heart muscle that can lead to heart failure and, ultimately, death.

“We basically try to rebuild a little piece of a patient’s heart in a dish,” says Hinson, who developed the technique during his postdoctoral fellowship.
He combines cardiac muscle cells with support cells, such as fibroblasts, and other key factors, including extracellular matrix proteins. Although these tiny, three-dimensional structures do not pump blood, they do contract rhythmically, and their beating strength can be studied.

Making a Difference

Hinson is applauded for his ability to move seamlessly between research, clinical practice, and teaching — the three prongs of an academic medical center’s mission. He’s able to do so, perhaps, because his own career began at the intersection of multiple scientific specialties.

As a University of Pennsylvania undergraduate, Hinson interned at DuPont in New Jersey to explore interests in chemistry and engineering. But he soon realized his passion for science needed a real-word focus. “I wanted to do science that made a difference in people’s health,” he says.

The same summer, he volunteered in the emergency department of a local hospital. Impressed by a cardiologist’s calm and collected manner in a crisis, and gaining interest in the heart, Hinson changed his career trajectory from engineering to medical school.

Hinson and his colleagues can isolate skin or blood cells directly from cardiomyopathy patients and coax them to form heart muscle cells, making it possible to study the biological effects of patients’ own mutations.

Hinson joined the laboratory of Dr. Robert J. Levy, a pediatric cardiologist and researcher at The Children’s Hospital of Philadelphia, working to harness gene therapy techniques to make artificial heart valves and other cardiovascular devices more durable. Through this early foray into biomedical research, Hinson deepened his interest in biomedical science and gained an appreciation of the work of a physician-scientist.

In Dr. Christine Seidman’s lab at Harvard Medical School, Hinson chose to lead a project on Björnstad syndrome, a rare, inherited syndrome characterized by hearing loss and twisted, brittle hair. At the time, little was known about the molecular causes of the disorder, although the genetic culprits were thought to reside within a large swath of chromosome 2. Using genetic mapping techniques and DNA sequencing, Hinson homed in on the precise mutations.

In addition to casting light on disease biology, he glimpsed the power of genomic information. “I was fascinated by the potential for understanding new genes that cause human diseases, and how important that was to society,” Hinson says.

Matters of the Heart

Throughout his medical training, Hinson noticed there were some significant stumbling blocks to gathering a deep knowledge of heart disease, particularly cardiomyopathies.

Cardiac muscle has essentially two paths toward dysfunction and ultimate failure. It can either dilate — become abnormally large and distended — or it can thicken. Both routes severely impair how well the heart performs as a pump. These conditions, known as dilated cardiomyopathy (DCM) and hypertrophic cardiomyopathy (HCM), can stem from pre-existing disorders of the heart, such as a previous heart attack or long-standing hypertension, or from DNA mutations.

Fueled by advances in genomics over the last two decades, more than 40 genes have been identified that underlie cardiomyopathy. But unlike diseases such as cystic fibrosis or sickle cell anemia, where it is fairly common for affected individuals from different families to carry the exact same genetic typo, it is exceedingly rare for unrelated patients with cardiomyopathy to share the same mutation. With such a complex genetic architecture, figuring out how the different genes and gene mutations contribute to heart disease has been an enormous challenge.


Dr. Travis Hinson speaks with others in his lab

Above: Dr. J. Travis Hinson gives a tour of his laboratory. Photo: Peter Morenus


Because of this formidable hurdle, drug discovery for the cardiomyopathies has languished. “There really has not been a paradigm-shifting drug developed for heart failure in the last 20 years,” says Hinson. Moreover, the few treatments that do exist are primarily aimed at controlling patients’ symptoms, not slowing or halting their disease.

Hinson aims to improve this picture. With his “heart-in-a-dish” technique, he and his team are now unraveling the effects of genetic mutations on cardiac biology.

The system harnesses multiple recent advances in both stem cell and genome editing technologies. With these capabilities, Hinson and his colleagues can isolate skin or blood cells directly from cardiomyopathy patients and coax them to form heart muscle cells, making it possible to study the biological effects of patients’ own mutations. Moreover, he can correct those mutations, or create additional ones, to further probe how genetic differences influence heart biology.

Part of the allure of Hinson’s approach is that it can be readily applied to study other forms of heart disease. It can also be leveraged for drug discovery, providing a platform to screen and test compounds with therapeutic potential in a wide range of cardiovascular diseases.

In addition to his research lab based at JAX, Hinson continues to practice cardiology at UConn Health. He helps run a specialized clinic focused on genetic forms of heart disease, as well as arrhythmias, connective tissue disorders, and other conditions.

“We have an exciting opportunity to provide clinical services in cardiac genetics in the corridor between New York and Boston,” he says. That means state-of-the-art genetic testing, including gene panels and genome sequencing, as well as genetic counseling for both patients and family members to help inform disease diagnosis and guide treatment. Although there are only a handful of treatments now available, Hinson believes this clinic will be uniquely poised to take advantage of a new generation of personalized treatments that are precisely tailored to patients’ specific gene mutations.

“Travis really is a quintessential physician-scientist,” says Dr. Bruce Liang, dean of UConn School of Medicine and director of the Pat and Jim Calhoun Cardiology Center at UConn Health.

“He has a remarkable ability to link basic science with important clinical problems, and his work holds a great deal of promise for developing new treatments for patients with cardiomyopathy. I wish there were two or three Travis Hinsons.”


Hinson’s beating heart tissue. Provided by Dr. Travis Hinson

UConn to Establish Genetic Counseling Master’s Program

illustration of genetic material


UConn has awarded $300,174 to seed a new Professional Science Master’s (PSM) Program in Genetics, Genomics, and Counseling. Graduates of the program will work with doctors and patients to interpret the results of genetic testing, a rapidly growing area in health care that needs more trained personnel. Once accredited, the program will be the first in Connecticut and the only one in New England at a public institution.

“Our students are anxious. They want to do this,” says Judy Brown, director of the diagnostic genetic sciences program in UConn’s College of Agriculture, Health, and Natural Resources’ allied health sciences department. Brown is spearheading the push for the program along with Institute for Systems Genomics director Marc Lalande and UConn Health genetics counselor Ginger Nichols.

Once accredited, the program will be the first in Connecticut and the only one in New England at a public institution.

New genetics research and techniques have made it easy for the average person to get a read on their genome, or whole genetic code. Celebrities, including Angelina Jolie, who have openly discussed their genetic risk factors for cancer, and companies, such as 23andMe, that will provide a basic genetic report for a fee, have increased demand enormously. But there’s a lack of trained people who can accurately interpret and explain the results of genetic tests, limiting the potential benefits.

Ideally, a doctor who identifies “red flags” within a patient’s family history that indicate increased genetic risk for disease will call in a genetic counselor. The counselor can take a detailed family history, determine the appropriateness of genetic testing, discuss benefits and limitations of testing to help the patient make an informed decision, and advise the patient on who else in their family might be at risk. If testing occurs and results indicate high genetic risk, counselors can help discuss the options to mitigate that risk.

As a result, genetic counseling is the fourth-fastest-growing occupation in Connecticut. Many UConn allied health sciences majors would like to enter the profession, Brown says, but there are only 34 training programs in the U.S., and the acceptance rate is below 8 percent.

Institutions including Connecticut Children’s Medical Center and The Jackson Laboratory (JAX) have expressed support for the program. Kate Reed, director of the Clinical and Continuing Education Program at JAX, says JAX would combine its experience translating genetic discoveries into clinical applications with UConn’s experience in this area to give the PSM graduates a solid understanding of the research behind clinical treatments.

The exact roles of JAX, Connecticut Children’s, and the other institutions who support the new PSM have not yet been defined. The program’s curriculum first needs to be approved and accredited. The first students are expected to start the program in fall 2018.

Lab Notes – Fall 2016

‘Morrbid’ RNA Could Be Key to Asthma Treatment

No.2 Pencil eraser erasing a piece of an RNA strand

Researchers have discovered a potential therapeutic target for inflammatory disorders that are characterized by abnormal myeloid cell lifespan, such as asthma, Churg-Strauss syndrome, and hypereosinophilic syndrome. Investigators including Adam Williams of UConn Health and The Jackson Laboratory named the novel long non-coding RNA ‘Morrbid’ (Myeloid RNA Regulator of Bim-Induced Death). They discovered that Morrbid tightly controls how long circulating myeloid cells live — which is key to maintaining the balance between fighting infection and exacerbating inflammation — by overriding a signaling mechanism that prevents premature immune cell death. In mice, deleting the gene helped protect them against inflammation and immunopathology. The findings were published online in Nature, Aug. 15, 2016.


Parents Living Longer is Good News for Offspring, Study Says

Father and young son laugh together and hug

A new study led by the University of Exeter and co-authored by the UConn Center on Aging, among other international contributors, shows that how long a person’s parents live can help predict how long the offspring will live, and how healthy the child will be as he or she ages. The study of 186,000 participants, aged 55 to 73 years and followed for up to eight years, is the largest of its kind. It found that a person’s chance of survival increased by 17 percent for each decade that at least one parent lived beyond age 70, and that those with longer-lived parents had lower rates of heart disease and other circulatory conditions, as well as cancer. The study was published in the Journal of the American College of Cardiology, Aug. 15, 2016.


PRP Limits Ill Effects of Osteoarthritis Treatment

red blood cells

Giving platelet-rich plasma (PRP) to patients undergoing treatment for osteoarthritis may limit the negative effects of the drugs used to manage their symptoms, according to a new study led by Dr. Augustus Mazzocca, director of the UConn Musculoskeletal Institute, and the University of Pittsburgh Medical Center. Osteoarthritis is the most common chronic condition of the joints, causing pain, stiffness, and swelling in approximately 27 million Americans. Powerful anti-inflammatory medicines and local anesthetics relieve pain and improve range of motion, but can also lead to tissue degeneration. In the study, published in the August issue of The American Journal of Sports Medicine, researchers found combining PRP with these treatments significantly reduced their toxic effect on the cells and even improved their proliferation.


Bath Salts 101: Pharmacist Explains Party Drugs

Synthetic party drugs with dangerous hallucinogenic properties, such as those sold commercially as “bath salts,” continue to pose a significant public health risk around the country. C. Michael White — head of the Department of Pharmacy Practice in UConn’s School of Pharmacy — published a comprehensive review of synthetic cathinones in the June 2016 issue of The Journal of Clinical Pharmacology to help clinicians recognize signs of abuse and properly treat patients with adverse events, ranging from psychosis to heart disease, from the drugs. This is the third in a series of articles on drugs including molly/ecstasy and GHB that he wrote to support clinicians. He is currently working on an assessment of synthetic marijuana.

dirty spoon holds 'bath salt' drug