Two leaders at the Wright Center are co-authors on articles in the New England Journal of Medicine this month.
Arun Sanyal, M.D., associate director for KL2 Career Development at the Wright Center, contributed to research showing the effects of semaglutide, a medication used to treat diabetes, on nonalcoholic steatohepatitis (NASH), a disease that affects millions of people in the U.S. each year.
The research was presented at a recent virtual conference of the American Association for the Study of Liver Diseases, where Sanyal also presented a field overview of the NASH landscape and recent clinical trial results. Sanyal leads and is part of multiple research projects on NASH at VCU, some showing promise for the treatment of the disease, which is the leading cause for liver transplantation in the U.S.
Antonio Abbate, M.D., Ph.D., associate director of hub research capacity at the Wright Center, contributed to research testing the safety and efficacy of an anti-inflammatory medication, rilonacept, on the rare disease of pericarditis.
Results of the study were presented at the American Heart Association’s recent Scientific Sessions. Abbate has spent many years studying heart diseases like pericarditis, exploring the link between heart conditions and inflammation.
Both Sanyal and Abbate have continued their research into heart and liver diseases this year, while leading and guiding clinical trials into the treatment of COVID-19.
Across the world, many years ago, doctors would prescribe unappealing concoctions of human and animal stool a treat a number of stomach ailments. And, in the last 10 years, clinical trials have begun to confirm why.
“There’s really a factory inside our bellies,” says Jasmohan Bajaj, M.D., a gastroenterologist and liver specialist at Virginia Commonwealth University. “Anything that we eat or drink, any medicines we take, when we get sick – the microbes are affected one way or the other. Either they are related to it, they process it, or they make us either resistant or prone to it.”
Bajaj is a major contributor to growing evidence that the unique collection of bacteria in our guts informs our health – sometimes in surprising ways. Fecal microbiota transplants – the newer, less unappealing version of that ancient treatment – are a big part of his research. And he’s leveraging the resources of the C. Kenneth and Dianne Wright Center for Clinical and Translational Research to accomplish his trials and study to become a leader in the field.
Working at a university with a Clinical and Translational Science Award (CTSA) from the National Institutes of Health, Bajaj has been awarded multiple grants that support his research into gut biomes and the uses of fecal transplants.
An R21 grant for 2017-18 helped Bajaj perform a randomized trial of fecal microbial transplant in patients with cirrhosis and hepatic encephalopathy.
This year he received another R21 grant to continue research into liver transplant outcomes, collaborating with a researcher another CTSA hub, the Columbia University Irving Institute for Clinical and Translational Research. The study will assess gut microbiota in patients with liver transplants in relation to their outcomes.
And he recently submitted an R01 to develop gut microbiota as a treatment for alcohol use disorder.
Bajaj also uses facilities maintained and funded by the Wright Center for his research. The Collaborative Advanced Research Imaging facility gives him access to a research-dedicated MRI scanner, which he’s using to analyze brain function in patients with cirrhosis before and after treating them with a gut-specific antibiotic.
A prolific summer of translational results
This summer, Bajaj published four articles showing the link between gut bacteria, cirrhosis and health. Read More
Before the COVID-19 pandemic’s onset in Virginia, Arun Sanyal, M.D., a liver specialist at VCU Health and associate director at the Wright Center, saw the promise of the experimental antiviral drug remdesivir against the disease. Determined to do right by patients, he contacted its manufacturers at Gilead Sciences, Inc. to push for VCU Health to be a clinical trial site, opening up access for patients when treatment options were scarce.
Because of Sanyal’s quick action, in March VCU Health became one of remdesivir’s first trial sites on the East Coast and in the country, eventually enrolling more than 70 participants in two trials of the drug before its emergency use authorization by the Food and Drug Administration in May.
With his experience as a leader of global multi-site clinical trials for drugs targeting nonalcoholic fatty liver disease, Sanyal was perfectly poised to bring potential COVID-19 treatments to Richmond within a week of the announcement of the city’s first case.
But he didn’t stop there: he and hospital leaders worked swiftly with the Virginia Hospital and Healthcare Association (VHHA) to make providers across Virginia aware of inpatient referral and transfer opportunities for the trials in case the drug could be useful for their patients with moderate to severe COVID-19 symptoms. Through it all, he never missed a morning round with COVID-19 inpatients and continued seeing liver patients and analyzing data with his team in the afternoons.
Since April, Sanyal, also a professor of internal medicine at VCU School of Medicine, has led several additional clinical trials to give patients access to more potential treatments.
Calvin Kiani, M.D., is a new junior faculty member in Internal Medicine at VCU and is a School of Medicine Rising Scholar. He will do clinical and translational research in the field of hepatology – on alcohol-related liver disease and alcoholic hepatitis. The research will focus on novel treatments, identifying biomarkers and developing models for predicting survival in this patient population.
Emily Heiston, Ph.D., is a post-doctoral fellow working in the Department of Cardiology at the VCU Pauley Heart Center. She joins us after five years at the University of Virginia, where she earned a Master’s and Ph.D. in Exercise Physiology. Her scientific interests include metabolism, biochemistry and endocrinology, researching how they’re affected by different disease states and how exercise can impact patient outcomes.
Madisyn Elam is a spring graduate of Virginia State University and plans to go on to medical school on an M.D.-Ph.D. track after a year of doing the master’s program full time. Elam participated in an inaugural program led by the Wright Center this summer that paired VSU undergraduates and recent graduates with VCU researcher mentors.
The master’s program attracts a diverse range of students at various stages in their careers with its interdisciplinary curriculum and dedicated mentorship. People who graduate from the program are prepared to apply translational science methods along the continuum of patient care, from the bench to the bedside.
Wright Center scholar Guizhi “Julian” Zhu, Ph.D., presented to 35 peers across the country yesterday about his research into nanomedicines.
Zhu has worked to develop experimental treatments that use nanoparticles or functional molecules to deliver drugs directly to lymph nodes and tumors for multiple modalities of tumor therapy. His research has implications for treatments across the spectrum of care, and his fellow researchers watching virtually came from a variety of backgrounds.
Zhu is a Wright Center KL2 scholar, through which program he receives funding for dedicated research time, as well as wraparound support services for his work. An assistant professor in VCU’s School of Pharmacy, Zhu has also received funding from the Wright Center’s Endowment Fund for health sciences research.
The hour-long talk was organized by the Georgetown-Howard Universities Center for Clinical and Translational Science, a Clinical and Translational Science Award hub like the Wright Center, as part of the KL2 Visiting Scholar Program. The scholar exchange program is an opportunity for KL2 scholars to visit partner schools for professional collaboration, networking and practice sharing.
Zhu recently received one of VCU’s 31 COVID-19 Rapid Research Funding Opportunity awards, which the Wright Center helped fund. His innovative drug delivery platform may prove useful in delivering an eventual COVID-19 vaccine.
The Wright Center has been on the front lines of the battle against COVID-19 since March.
As Virginia Commonwealth University’s home for interdisciplinary human health research, the center is uniquely positioned to act as a bridge between the physicians, faculty, researchers and staff that are engaged in fighting the pandemic on multiple fronts.
And it’s done just that.
Before the government-mandated shutdown took effect, several proposed projects had been uploaded to VCU’s research management system run out of the Wright Center, OnCore. And center staff had activated to help shepherd protocols through the Institutional Review Board and other processes.
The Wright Center has worked diligently to prioritize and fast track other drug treatment trials based on the best available science and the drugs’ potential for large-scale efficacy. The center’s director, F. Gerard Moeller, M.D., leads a committee with several other center faculty that works to assess and evaluate proposed COVID-19 trials.
At least seven COVID-19 drug treatment trials have activated, many in record time. Trials that might take months to get off the ground have found approval within days, thanks to the Wright Center and staff at the Office of the Vice President for Research and Innovation (OVPRI).
Wright Center Associate Director Antonio Abbate, M.D., Ph.D, is a lead on two studies that tackle the dangerous inflammatory response that COVID-19 patients sometimes experience:
Sarilumab, which was developed for rheumatoid arthritis, and
Canakinumab, which was developed to treat a series of rare auto-inflammatory diseases and a type of juvenile arthritis.
Benjamin Van Tassell, Pharm.D., a former KL2 scholar and now a member of Wright Center’s KL2 Oversight Committee, is involved in the latter trial. His and Abbate’s long-standing research into inflammation, supported in part by the Wright Center, has been crucial to VCU’s ability to bring cutting-edge treatment to its patients during COVID-19.
In May, with the help of Wright Center Clinical Research Unit staff, clinical trials for some of the experimental COVID-19 treatment drugs were expanded to VCU Health’s Community Memorial Hospital in South Hill, Virginia, expanding access to those drugs.
In addition to the drug treatment trials, the Wright Center has worked to fast track projects like a potential treatment for COVID-19 using the plasma of coronavirus survivors. More than a dozen registries for analyzing COVID patient data and vitals are underway. And multiple technologies and devices that fill critical equipment needs are in development or pending approval.
Feeding all this new research is an influx of funds flowing toward virus-related projects.
The Wright Center contributed $100,000 to the OVPRI’s COVID-19 rapid research funding opportunity, which has yielded grant awards to 31 recipients, including several clinical and translational science projects. Wright Center KL2 Scholar Guizhi “Julian” Zhu, Ph.D., was one of those recipients, for his work on a simple, at-home vaccine delivery mechanism.
The Wright Center staff and research administrators continue to contribute the research infrastructure and compliance expertise to projects that seek to fill worldwide gaps in equipment supply.
The Wright Center was instrumental in connecting interdisciplinary researchers and clinicians for a 3D-printed ventilator, the plans for which will be made freely available. And Wright Center Researcher Stephen L. Kates, M.D., helped develop a sterilization pilot program to safely decontaminate N95 masks for VCU Health employees.
Much of the research that was underway when COVID-19 hit has been paused, and the Wright Center worked with OVPRI to create research continuity guidance, so that researchers would have some template for adapting their important work.
Three VCU faculty joined the leadership team of the Wright Center – official today. They bring a breadth of expertise and experience to the center’s mission of providing the infrastructure and resources that promote interdisciplinary human health research at VCU.
Robert Winn, M.D., who became director of VCU’s Massey Cancer Center in December, joins the Wright Center leadership team as an expert in lung cancer and community-based health care, including creating community-to-bench health models that combine discovery and implementation sciences into a single health delivery and research system. Winn will bring expertise to community collaboration and recruitment, translational workforce development in underrepresented communities, and faculty training techniques for improving diversity.
Winn comes from University of Illinois at Chicago where he has served as director of their cancer center and as associate vice chancellor of health affairs for community-based practice at the University of Illinois Hospital and Health Science System.
Robert L. Findling, M.D., MBA, joins Wright from the Department of Psychiatry, which he became the chair of last year. Findling is a renowned child psychiatrist and has over 20 years of experience conducting clinical research in child, adolescent and adult psychiatry fields – with expertise in pediatric psychopharmacology, acute efficacy studies, long-term treatment studies, characterization of young people with mental illness, and how to conduct successful clinical trials. He has served as principal investigator and as a coordinating principal investigator on multi-site clinical trials and longitudinal studies funded by the National Institute of Mental Health and the Eunice Kennedy Shriver National Institute of Child Health and Human Development.
Vimal K. Mishra, M.D., an associate professor of medicine and health administration, joins the Wright Center as a researcher who has been heavily involved in the development of VCU’s telemedicine program. Misha will oversee informatics methods to enhance community engagement, such as Project ECHO (Extension for Community Health Outcomes), which builds mentoring based learning networks that connect subject-matter experts to practicing providers, clinicians and social health care professionals across Virginia. Currently, Project ECHO offers services in the areas of opioid addiction, sickle cell disease management and palliative care.
“My research is focused on improving equity in access to HIV care,” Kimmel said. “The KL2 award from the Wright Center supported dedicated time for me to pursue additional training and conduct critical foundational work related to my domestic research agenda. It set the stage for my professional development and career independence.”
The KL2 program provides early-career researchers with protected time to help their findings benefit human health more quickly. It also provides mentorship and career development opportunities to help researchers like Kimmel become successful, independent translational scientists.
After completing the three-year KL2 program in 2016, Kimmel submitted a grant application to the National Institute on Minority Health and Health Disparities that was based upon her Wright Center-supported research. She was awarded a four-year R01 by NIMHD to expand her KL2 studies and examine the influence of structural barriers on the quality of HIV care and population health in the U.S. south. “The early career training supported by the KL2 has resulted in multiple extramural federal research grants and important contributions to knowledge on the role of structural barriers in HIV care in the U.S.,” Kimmel said.
In recognition of her achievements, the VCU Office of the Vice President for Health Sciences appointed Kimmel as one of four 2019 Blick Scholars. Created with a $2 million bequest from the George and Lavinia Blick Research Fund, the Blick Scholars Program endowment is awarded every four years to medical researchers on the MCV Campus. The award recognizes scholars with documented growth toward national prominence, a record of external research funding, and collaborative scholarship. “Rather than recognizing a specific project, the program acknowledges an overall trajectory of scholarship growth,” Kimmel said.
Through the Blick Scholars Program, Kimmel will receive an annual award of approximately $25,000 a year (based on market performance) to support her research for four years. She will apply the funding toward studying how structural barriers to HIV care – such as geographic accessibility and physicians payment rates – influence quality of care and how policy changes can improve inequities in the impact of the barriers on quality of care. Internationally, she will work toward projecting how different HIV clinical policies impact health outcomes and new HIV infections over time. She will also study the cost-effectiveness of various clinical policies. “My goal is to improve access to HIV care in very resource-limited settings,” she said.
“I sometimes feel helpless because I can’t do much for them at that moment other than saying some kind words,” Zhu said. “Those are the moments that help me focus on my research to potentially have an impact that can change or improve therapeutic outcomes for cancer patients.”
Leveraging an extensive background in engineering, chemistry, and pharmacology, Zhu leads a research team of six postdocs and graduate students, as well as multiple undergraduate students and visiting scholars. His team designs targeted drug delivery systems and develop cancer nanomedicines such as nucleic acid nanovaccines for enhanced therapeutic benefit. Nanovaccines dispense microscopic particles into the immune system to stimulate a response against cancer cells. They hold promise for treating disease more effectively than existing vaccines. Zhu tests a variety of nucleic acids, including immunomodulatory DNA/RNA, gene-expression modulation DNA/RNA, drug-encoding mRNA or gene-editing nucleic acids.
Zhu currently holds several grants to support studies on nanovaccines for glioma, a tumor of the brain and spinal cord, and melanoma, the deadliest form of skin cancer.
Under the mentorship of VCU School of Medicine professor Steven Grossman, M.D., Ph.D., Zhu holds an American Cancer Society Institutional Research Grant to study the combination of immunotherapy and immuno-activating chemotherapy to treat melanoma. He is also a principal investigator on a VCU Massey Cancer Center pilot project that will explore the combination of a nanovaccine, immune re-energizing drugs and radiation therapy to treat glioma in mouse models.
“This project is really exciting because there isn’t a durably effective treatment option for glioma,” Zhu said. “We hope that by using radiation we can jump-start the tumor microenvironment to make immunotherapy more effective.”
Zhu grew up in China, where he earned a bachelor’s degree in biotechnology from Nankai University. He later moved to the U.S., where he earned a doctorate in medical science and completed a postdoctoral fellowship in cancer nanomedicine at the University of Florida. He finished a second postdoctoral fellowship in cancer immunotherapy and bioimaging at the National Institute of Biomedical Imaging and Bioengineering in Maryland. During this time, Zhu collaborated in well-established laboratories to engineer and image nanomedicines. It was after this fellowship that he focused his research on cancer immunotherapies.
“The scientific combination of pharmaceutics and cancer research offers an ideal environment for me to continue my career at Massey,” he said.
Zhu has published more than 70 articles in peer-reviewed journals, including Nature Communications and Proceedings of the National Academy of Sciences. His publications have been cited by peers more than 4,500 times in the past five years. He is a member of the American Chemical Society, the Oligonucleotide Therapeutics Society and the Society for Immunotherapy of Cancer. He received a Distinguished Scientist Award from the National Institutes of Health in 2017 and was awarded the Alan M. Gewirtz Memorial Fellowship by the Oligonucleotide Therapeutics Society in 2013.
He lives with his daughter and mother in Richmond, and the family awaits the arrival of his wife, who is close to finishing her doctoral degree in food science and nutrition in Maryland.
Re-purposed from an article by Blake Belden, VCU Massey Cancer Center
A new program made possible by a $4 million endowment established by longtime Virginia Commonwealth University benefactor C. Kenneth Wright is connecting the next generation of health sciences researchers with the resources and training they need to support their work.
The C. Kenneth and Dianne Wright Physician-Scientist Scholars Program welcomed its inaugural class earlier this year. The program that is open to VCU School of Medicine M.D.-Ph.D. students in their second year or further of graduate school training offsets the students’ tuition, fees, and stipends during medical school years. It also provides the students with up to $3,000 each year, which can be applied toward travel to a meeting to present results of their clinical or translational research, defraying the cost of a United States Medical Licensing Examination, or defraying the cost of residency program interviews. Additionally, it can be applied to partially defer medical school tuition and stipend costs for each scholar.
“The students were selected on the basis of their outstanding proposals for translational or clinical research projects,” said M.D.-Ph.D. program director Michael Donnenberg, M.D. VCU School of Medicine professor emeritus and former M.D.-Ph.D. program director Gordon Archer, M.D., chaired the committee that reviewed program applicants and selected three students for the awards based on their application’s scientific merit, feasibility and translational emphasis.
Fourth-year Ph.D. student Teja Devarakonda will study how the heart functions during a heart attack.
“Heart attacks damage the heart muscle tissue and impair the heart’s ability to provide blood to bodily organs,” he said.
With support from the Wright Physician-Scientist Scholars Program, Devarakonda and his research team will investigate the protective properties of a pregnancy-associated hormone called relaxin, which previous studies have shown as effective at reducing damage to cardiac tissues over time after a heart attack.
“My project specifically involves studying the protective effects of over-expressing a receptor for relaxin in a mammalian heart via a gene therapy-based approach after a heart attack,” Devarakonda said. “We hope the research can lead to further insight into translational approaches to benefit patients suffering from heart attacks and heart failure.”
After graduating, Devarakonda plans to pursue a residency in internal medicine and would like to specialize in cardiology. “The Physician-Scientist Scholars Program will provide me with the necessary framework for training and financial support as I progress through the rest of the M.D.-Ph.D. program,” he said.
Third-year Ph.D. student Graeme Murray already applied a portion of the scholarship funding to pay for travel to meet with a research team at the University of California Los Angeles Jonsson Comprehensive Cancer Center, where he helped a research team build a microscope to help doctors determine if a cancer patient will benefit from a given therapy. The microscope, which Murray helped develop with his research team at VCU, tracks changes in mass of tens of thousands of single cells from patient tumors.
“If single cells from the patient are resistant to a given therapy, the cells will continue to grow in mass,” Murray said. “But if the cells are sensitive to the therapy, they will decrease in mass over time and die.”
The screening methodology allows his research team to identify sub-populations of resistant cells that have been shown to lead to drug resistance in patients. He hopes for the methodology to one day be used by doctors to inform therapy choices.
“With success, doctors will be able to identify patients who will benefit from a given therapy before trying it,” Murray said. “This could ensure patients receive the optimal therapy for their cancer.”
In the coming years, Murray hopes to apply funding from the scholarship toward attending the American Association for Cancer Research and Cancer Research UK’s joint conference on engineering and physical sciences in oncology. “The Physician-Scientist Scholars Program has allowed me to travel across the country to work with collaborators,” he said. “In the future, it will allow me to travel to conferences to share our work and learn from others in the field of oncology research.”
Eric Kwong, who has completed the graduate school training portion of the M.D.-Ph.D. program and is in his third year of medical school training, will apply the scholarship to support his research aimed at modulating a specific enzyme to reduce liver disease severity. Through the course of his research, he will test drug compounds in mice in an attempt to improve disease progression.
“The goal of my research is to understand the disease process that leads to irreversible liver injury, scarring, and non-functioning liver,” Kwong said. Non-alcoholic liver disease and alcoholic liver disease are the most common liver diseases worldwide, but no effective pharmacologic treatments exist for them. “Ultimately, I want to contribute to the development of therapeutic drugs that can reduce or reverse the disease progression,” he said.
After graduating, Kwong plans to pursue a medical residency and specialize in gastroenterology. “I want to take care of patients who have various gastrointestinal and liver diseases while conducting translational research for the development of novel treatment options for diseases that we do not yet have cures,” he said. “The Physician-Scientist Scholars Program will help me extend the fundamental scientific findings I have discovered in the laboratory and test those ideas in mice, with the goal of discovering potential drug targets for non-alcoholic fatty liver disease and alcoholic liver disease.”
In addition to the $4 million Physician-Scientist Scholars Program endowment, Wright’s $16 million gift to name the Wright Center in 2015 established six Distinguished Chairs in Clinical and Translational Research.
“Mr. Wright’s support has enabled us to aid VCU in recruiting distinguished researchers from around the country, in addition to helping us prepare the best and brightest students for careers along the spectrum of translational science,” said Wright Center director F. Gerard Moeller, M.D.