VCU’s Jordana Kron is searching for answers to a mystery disease

By Anne Dreyfuss
C. Kenneth and Dianne Wright Center for Clinical and Translational Research

Jennifer Jordan, Ph.D, left, and Jordana Kron, M.D., are working on a new treatment for sarcoidosis, an inflammatory condition that can lead to cardiac failure when it affects the heart. (Photo by Thomas Kojcsich, University Marketing)

A disease that has no cause or cure, sarcoidosis affects people of all ages throughout the world. Once considered a rare disease, the inflammatory condition now affects about 40 in every 100,000 African Americans in the U.S. and about five in every 100,000 white people. It occurs in all races and in men and women, but is most common among African American females ages 20 to 40.

The disease most commonly affects the lungs, but can involve almost any organ system including the skin, eyes, joints and heart. Cardiac involvement, which occurs in up to 25% of patients with sarcoidosis in other organs, can lead to life-threatening heart rhythm problems and heart failure.

“The field of cardiac sarcoidosis, and sarcoidosis in general, really needs new mechanistically driven therapies,” said Jordana Kron, M.D., an associate professor in the Virginia Commonwealth University School of Medicine and a cardiologist at the VCU Health Pauley Heart Center.

This month, which is National Sarcoidosis Awareness Month, Kron was awarded a $50,000 Pauley Pilot Research Grant to investigate a new treatment protocol for cardiac sarcoidosis. The 15-month grant will be used to evaluate the efficacy and safety of using an interleukin-1 blockade to treat patients who present with cardiac sarcoidosis. The study is the first of its kind to explore the new treatment paradigm.

“A new, safe and effective treatment could be life-altering for patients with cardiac sarcoidosis. It may also open the door for new therapies for cardiac sarcoidosis and other inflammatory heart diseases in the future,” said Kron, a translational science scholar at the VCU C. Kenneth and Dianne Wright Center for Clinical and Translational Research.

Interleukin-1 is a protein whose presence indicates inflammation in the body. Kron’s research aims to evaluate if using medication to block the protein will help treat cardiac sarcoidosis.

“Corticosteroids are the most commonly used treatment for sarcoidosis, but there is little data showing their efficacy and they have significant side effects,” Kron said. “Interleukin-1 is the prototypical cytokine that plays a role in most inflammatory processes. Blockade of the protein has been shown to be effective in many types of heart disease.”

While cardiac sarcoidosis is the focus of Kron’s research, she is optimistic that — if shown to be effective — the blockade could be used to treat other forms of heart disease.

Tackling cardiac sarcoidosis

VCU has led clinical and translational research of cardiac sarcoidosis for nearly a decade and VCU Health is home to the Multidisciplinary Sarcoidosis Clinic, the only center of its kind in Virginia. At the clinic, located at the VCU Health Stony Point Campus, patients are able to meet with specialists in pulmonology, cardiology, electrophysiology and rheumatology during a single appointment.

In 2011, VCU researchers teamed with researchers at the University of Michigan and the University of Colorado to start the international Cardiac Sarcoidosis Consortium. Kron is a founding member. The consortium is a prospective, multicenter registry that tracks cardiac sarcoidosis patients worldwide. It includes demographic, clinical, medication and imaging data from more than 25 contributing centers in the U.S., Europe and Asia.

Kron attributes much of the headway she has made in researching sarcoidosis to support from the Wright Center, Virginia’s first institution to receive a Clinical and Translational Science Award from the National Institutes of Health. Antonio Abbate, M.D., Ph.D., associate director of the Wright Center, has served as a mentor and co-investigator on Kron’s research. Abbate, a cardiology professor at the VCU School of Medicine and a cardiologist at the Pauley Heart Center, also will share his expertise on cardiac inflammation and interleukin-1 blockers throughout the study. F. Gerard Moeller, M.D., director of the Wright Center, and Patrick Nana-Sinkam, M.D., the center’s KL2 program co-director, provided mentorship, support and feedback on grant writing for the project as well.

“Support from the Wright Center has enabled me to build on existing relationships and create new collaborations to help advance our understanding and treatment of this complex disease,” Kron said.

Kenneth Ellenbogen, M.D., chair of the Pauley Heart Center’s Division of Cardiology, also provided significant support for Kron’s research.

“I would not be where I am today without Dr. Ellenbogen’s mentorship,” she said. “He has played an invaluable role in my research career.”

Gathering critical data

Kron, who last October was awarded an endowment fund through the Wright Center to further support her research, is joined in the study by Jennifer Jordan, Ph.D., an assistant professor in the VCU College of Engineering Department of Biomedical Engineering and director of the Cardiovascular MRI Core Lab at the Pauley Heart Center. Jordan’s research focuses on translational and clinical cardiovascular MRI techniques and cardiac magnetic resonance tissue characterization in patients who have received chemotherapy for breast cancer. For this study, she will be using her expertise in cardiac magnetic resonance to help assess inflammation in cardiac sarcoidosis and evaluate responses to treatment.

The Pauley Pilot Research Grant Program, which is made possible entirely by philanthropy, supports early stage research by physicians and scientists working to advance heart health. The program allows investigators to test novel ideas and gather enough data to apply for major research grants from institutions such as the NIH.

Kron plans to submit a proposal for external funding by February 2021.

“The results of this research will help me gather critical data to inform applications for larger grants later,” she said.

Inaugural Virginia Clinical Research Conference inspires and strengthens the commonwealth’s clinical research enterprise

T.J. Sharpe addresses the crowd at the Virginia Clinical Research Conference
Metastatic melanoma survivor and clinical research participant T.J. Sharpe talks to Virginia Clinical Research Conference attendees about how clinical trials saved his life. Photo by Kevin Morley, VCU University Relations.

By Anne Dreyfuss
C. Kenneth and Dianne Wright Center for Clinical and Translational Research

The ballroom inside the Hilton Hotel in downtown Richmond was standing room only on Friday morning, when more than 200 clinical research professionals from across the commonwealth gathered for the inaugural Virginia Clinical Research Conference.

“At the end of every clinical trial, there is a family waiting,” keynote speaker T.J. Sharpe said to the crowd of clinical and translational scientists who had assembled for the first conference aimed at strengthening the clinical research enterprise throughout the state. The conference, titled “Engagement: 2019,” was hosted by the Virginia Commonwealth University C. Kenneth and Dianne Wright Center for Clinical and Translational Research with participation from VCU Health and the VCU Office of Research and Innovation.

“We designed the conference as an opportunity to work with academic medical centers across the state,” said Wright Center Director F. Gerard Moeller, M.D. “We wanted to identify ways to become more engaged with one another, as well as the communities we serve, as we work to design, test, and deliver innovative treatment options for patients.” In addition to VCU and VCU Health, attendees hailed from institutions including Eastern Virginia Medical School, the University of Virginia, Virginia Tech Carilion School of Medicine, Inova Health System and Bon Secours Health System.

In his presentation, Sharpe talked about how enrolling in a clinical trial saved his life. In August 2012 — just weeks after the birth of his second child — Sharpe was diagnosed with metastatic melanoma, which is the most dangerous form of skin cancer. His physician gave him less than two years to live. “My purpose wasn’t to be a cancer survivor,” Sharpe said. “It was to be a dad, husband, brother and uncle, but to do that I needed to find a treatment that would give me a chance to fulfill my purpose.”

Knowing the five-year survival rate for metastatic melanoma hovered between 15 and 20 percent, Sharpe enrolled in two clinical trials to try to beat his long odds of survival. Now nearly seven years after the diagnosis and living cancer free, the Fort Lauderdale, Florida-resident has forged a career as a patient advocate and clinical trial experience expert, making it his life’s mission to share the value of clinical research with audiences around the country. “I’m dance dad now on Tuesdays, taking my daughter back-and-forth to dance,” Sharpe said. “These days, my wife and I take the kids on white water rafting trips and go hiking in Maine.”

Sharpe urged the crowd of clinical research professionals to think of him and countless others like him who depend on research they do every day. “My other purpose now is to bring my message to the clinical research world and implore those who have the ability to affect the lives of patients to do so,” he said. “It gave me hope to know there were researchers out there doing incredible work and I wanted to be a part of that. I wanted the opportunity to help other people and make the world a better place through clinical trial participation.”

Wright Center clinical research KL2 scholar Mario Acunzo, Ph.D., speaks with Wright Center director F. Gerard Moeller, M.D., about his research poster. Photo by Kevin Morley, VCU University Relations.

Throughout the daylong conference, attendees discussed how they can work together to help more people like Sharpe. At packed workshops centering on topics including how to engage the community, use big data and work more closely with investigational pharmacists, attendees shared perspectives and collaborated on new opportunities in clinical research.

“Uncovering your unconscious bias makes all the difference in the world as a clinical researcher,” said VCU School of Nursing associate professor Jo Lynne Robins, Ph.D. Robins was a panelist at an interactive workshop on engaging community partners in the practice of clinical research, where researchers and community health providers exchanged experiences and advice for how build better relationships. “The reason we do research is because we want to make a difference in patients’ lives,” Robins said. “We need to find common ground where we’re all committed to the same thing.”

At a breakout session on research ethics, Francis Macrina, Ph.D., posed a hypothesis that it should be possible to tailor a curriculum of responsible research conduct aimed at clinical and translational scientists. “We can and should begin to tailor responsible conduct of research curricula to specific audiences. One size doesn’t fit all anymore,” said the former vice president for research and innovation at VCU.

At the end of the conference, prizes were awarded for poster competition presentations. Thomas Corey Davis, Ph.D., who is an assistant professor and vice chair of clinical affairs in the VCU College of Health Professions Department of Nurse Anesthesia, was awarded the best poster in the category clinical research best practices/quality improvement/process innovations. Elizabeth Krieger, M.D., who is a fellow in the VCU School of Medicine Division of Hematology, Oncology and Palliative Care, was awarded the best poster in the category clinical science research.

“We hope for you to take these discussions beyond this conference,” said Wright Center associate director Antonio Abbate, M.D., Ph.D. At a panel discussion wrapping up the day’s events, Abbate urged conference attendees to apply what they had learned at the conference to their daily research. “There is a person, a face and a smile behind everything that we do,” he said. “Clinical research is an instrument that allows beautiful stories to occur.”

 

Poster competition awardees:

Clinical research

best practices/quality improvement/process innovations:
Title:“Assessing a Novel Method to Reduce Anesthesia Machine Contamination: A Prospective, Observational Trial”

Authors: Thomas Corey Davis, Ph.D., CRNA; Beverly George-Gay, MSN, RN; Praveen Prasanna, M.D.; Emily M. Hill, Ph.D.; Brad Verhulst, Ph.D.; Chuck J. Biddle, Ph.D., CRNA

Clinical science research:
Title: “A Novel KIR-HLA Interaction Scoring System and its Effect on Transplantation Outcomes after HLA Matched Allogeneic Hematopoietic Stem Cell Transplantation”

Authors: Elizabeth Krieger, M.D.; Roy Sabo, Ph.D.; Victoria Okhomina; Catherine Roberts, Ph.D.; Sunauz Moezzi; Caitlin Cain; Marieka Helou, M.D.; John McCarty, M.D., Rizwan Romee M.D.; Rehan Qayyum M.D. MHS; Christina Wiedl, D.O.; Amir Toor, M.D.

Let’s talk about sex: Gender differences in research and health care take center stage at annual Women’s Health Research Day

 

Gretchen Neigh, Ph.D., presents at Women’s Health Research Day. Photo courtesy Lisa Phipps.

No topic was off limits at Women’s Health Research Day on April 9, where more than 70 Virginia Commonwealth University faculty, students, staff and community members gathered to discuss how sex and gender differences impact bench-to-bedside research and clinical outcomes.

“There are fundamental differences between men and women that need to be considered in all levels of health care,” said Pam Dillon, Pharm.D., who is a research liaison at the C. Kenneth and Dianne Wright Center for Clinical and Translational Research. Dillon serves on the professional advisory board of the VCU Institute for Women’s Health, which has hosted the annual event for 15 years as a way to celebrate and promote research activities in women’s health at VCU.

Susan Kornstein, M.D., welcomes attendees to Women’s Health Research Day. Photo courtesy Lisa Phipps.

“The goal of Women’s Health Research Day is to bring together researchers from across the university and health system to showcase and share their work,” said VCU Institute for Women’s Health executive director Susan Kornstein, M.D.

The day included a plenary symposium, poster awards and a reception highlighting women’s health research by VCU faculty members and students.

“We have some work to do to move toward equitable representation of sex and gender in research,” said Gretchen Neigh, Ph.D., an associate professor in the Department of Anatomy and Neurobiology at VCU School of Medicine.

Neigh, who serves as the director of translational research at the VCU Institute for Women’s Health, chaired the plenary symposium and presented on why sex matters in research. During her talk, she dispelled conventional excuses for not including women in clinical research and reviewed studies on sex and gender bias in medical school and basic science laboratory settings.

“Simply including women in your research team increases the likelihood that you will pay attention to sex and gender differences in your research outcomes,” Neigh said. She encouraged the audience to pay attention to sex within experimental designs and create diverse research and clinical teams to improve the odds of equity. “Sex and gender impact nearly everything,” she said. “If you interact with other humans on any level of the health care

continuum, you need to be aware of how sex and gender can impact health.”

Poster presentations focused on women’s health, as well as sex and gender differences. They were reviewed for research originality, scientific rigor, and women’s health relevance, with awards presented for posters in basic science, clinical and translational research, and community and public health research.

“The missions of the Wright Center and the VCU Institute for Women’s Health are similar,” said Dillon, who helped plan the conference and served as a judge for the poster competition. “The VCU Institute for Women’s Health is committed to training and supporting women in science, and the Wright Center’s research and training programs provide a strong foundation to help the institute with that mission.”

Poster awardees and VCU Institute of Women’s Health leadership. From left-to-right: Susan Kornstein, M.D., Zaneera Hassan, Candace C. Johnson, Hope Wolf, Albert Ksinan, Dace Svikis, Ph.D., Lisa Phipps, Ph.D., Pharm.D.

Congratulations to our Top Docs

Five Wright Center clinician-scientists were recognized as “top docs” in Richmond magazine‘s annual listing of leading physicians in the Richmond region. The below-listed physicians were chosen by their peers and provide a wide range of care in multiple specialties at VCU Health.

Congratulations to this year’s winners!

  • Director F. Gerard Moeller, M.D., Addiction Medicine
  • Associate director Antonio Abbate, M.D., Ph.D., Cardiology
  • Network Capacity Core project lead David Cifu, M.D., Physical Medicine and Rehabilitation
  • Hub Research Capacity Core co-investigator Judy Voynow, M.D., Pediatric Pulmonology
  • 2013 Endowment Fund recipient Anshu Gupta, M.D., Pediatric Endocrinology

Q&A with Wright Center researcher Brian A. Taylor, Ph.D.

Photo courtesy Dan Wagner, VCU College of Engineering

By Emi Endo
VCU College of Engineering

A medical imaging physicist, Brian A. Taylor, Ph.D., is an assistant professor in the VCU Department of Biomedical Engineering and a researcher at the C. Kenneth and Dianne Wright Center for Clinical and Translational Research.

1. What are you working on right now?

I’m working on innovative ways to measure brain function and structure with magnetic resonance imaging. As an MRI physicist, I design unique scans to noninvasively image tissues or measure physiological mechanisms in the human body. This can include measuring brain activity during mental tasks, visualizing cortical and white matter structures and measuring the quantity of neurotransmitters in different regions of the brain. We are particularly interested in the effects of substance use on the brain and how addiction drives the continuing use of potentially harmful substances like opioids, cocaine and alcohol.

2. What do you hope to achieve with this research?

By measuring differences between a person who is addicted to harmful substances and someone who is not, we can see which parts of the brain are driving addictive behavior and tailor treatments based on the data we collect. In addition, we can see how treatments for substance use are working in restoring the person’s function to what we see in people who are not addicted to drugs or alcohol.

3. How will this research make a difference?

Drug and alcohol use, particularly opioid use, are at epidemic levels in the U.S. Here, we have the opportunity to provide high-quality imaging-based research to help our VCU and VCU Health colleagues who are researching drug use by giving them important data to help them investigate and find the best treatments. VCU has an astounding collaborative environment with the VCU Institute for Drug and Alcohol Studies and the Collaborative Advanced Research Imaging facility that houses a research-dedicated MRI system. Having CARI here helps tremendously in getting the data we need to investigate several conditions including addiction, liver disease and heart disease.

4. Tell us about how you are investigating this.

We use two main techniques: functional MRI and magnetic resonance spectroscopy. In fMRI, when part of the brain is activated — by a mental or physical task, or even at rest — the exchange of oxygenated and deoxygenated blood in addition to blood flow changes can be measured. This can then be processed to image areas of activation in the brain. We can also use this to measure how different regions of the brain communicate with each other over a period of time. In MRS, we can measure the amount of certain metabolites or neurotransmitters in the brain. We are particularly interested in the neurotransmitters glutamate and gamma-aminobutyric acid, as they are usually altered with drug and alcohol use.

5. What’s the biggest challenge right now?

When people usually think of MRI, it is of a radiologist viewing a scan in order to make a diagnosis. While this is certainly true, there is an abundance of quantitative data that can come from these scans. This quantitative approach requires a dedicated team to carefully process gigabyte-sized data sets for each participant scanned. This can be anything from looking at changes in cerebral blood flow, visualizing white matter tracts or even measuring the amount of fat in the liver in chronic alcohol use. While it is a challenge and takes time to process a lot of data, it is very rewarding and fun to come up with new ways to measure things inside the body in a way that couldn’t be done before.

Meet the Team: Pam Dillon

At the Wright Center, we seek to advance science and foster partnerships that accelerate translational research for the betterment of human health. Our team members come to work every day ready to transform laboratory discoveries into treatments for patients, engage communities in clinical research and train a new generation of clinical and translational scholars, all with the shared goal of bridging the gap between scientific theory and practical medicine.

Each month, we will highlight one member of our team who is contributing to our shared mission of advancing science and fostering partnerships that accelerate translational research for the betterment of human health.

For a full list of staff members, please visit cctr.vcu.edu/aboutus/staff.

Cancer survivor advocates for clinical trial participation

Cancer survivor and clinical trial advocate T.J. Sharpe, bottom right, will speak at the inaugural Virginia Clinical Research Conference on April 12.

T.J. Sharpe was diagnosed with metastatic melanoma just weeks after the birth of his second child in August 2012. Sharpe had overcome the most dangerous form of skin cancer 12 years prior, so news of the recurrence came as a shock. What followed was even more shocking, when doctors told him he had less than two years to live. Not willing to let his life be defined by a diagnosis, Sharpe enrolled in two clinical trials to try to beat his long odds of survival.

Now nearly seven years after that second diagnosis and living cancer free, the Fort Lauderdale, Florida-resident has forged a career as a patient advocate and clinical trial experience expert, making it his life’s mission to share the value of clinical research with audiences around the country. In his presentations, Sharpe speaks about the patient experience for late-stage cancer treatments, immunotherapies and clinical trials. Along the way, he brings a message of hope from the perspective of a patient who is on the road to recovery.

On April 12, Sharpe will visit Richmond to speak about his experience with clinical trials at the Virginia Clinical Research Conference. The inaugural, statewide conference will be held at the Hilton Richmond Downtown Hotel from 7:30 a.m. to 5 p.m. It brings together clinical research professionals from across Virginia to share perspectives, discuss best practices, and collaborate on new opportunities in clinical research, all with the shared goal of strengthening the clinical research enterprise in the state.

Ahead of his talk, VCU News spoke with Sharpe about the value of clinical trial research and what he hopes to share with conference attendees.

When you found out the melanoma had returned, what was your initial reaction?

I was in disbelief initially, but as the week in the hospital went along I learned more about how difficult it can be to keep melanoma from recurring. I was lucky it had stayed dormant so long, as it was the same melanoma from 12 years prior. So my initial disbelief turned into resolve, knowing the difficult journey I was undertaking.

When was the opportunity to participate in a clinical trial presented to you, and why did you decide to enroll?

It was only presented to me after three oncologists offered varying treatment options. One offered chemotherapy, while two others offered a newly approved immunotherapy. Luckily I had done my research and pushed for the best possible treatment available. I finally found something from the fourth oncologist that we believed was the best chance at giving me a durable response. I picked that clinical trial because it incorporated everything I had learned about the growing field of immunotherapy — it was a combination therapy that included personalized medicine and immunotherapy rather than chemotherapy. Additionally, it had shown significant promise in similar trials to have a continued response years after the treatment.

When that trial failed, why did you decide to try another?

At that point, we were open to pretty much anything. But in the six months between diagnosis and the first trial’s failure, the success of the anti-PD-1 drugs surged. We were sure the best possible option for me at that point was one of those checkpoint inhibitors, and that particular one was the furthest along in development. [Anti-PD-1 immunotherapies aim to block a pathway that shields tumor cells from cancer fighting immune system components, thus enabling the body’s immune response to better attack cancer.]

How have you benefited from participating in clinical trials?

Not only have I become completely clear of cancer, this experience has given me insights into the clinical trial advocacy world. My career is now centered on representing the patient voice in drug development and clinical trial research. I get a chance to help others find the right treatment at the right time for them.

What will be your message to people who attend the Virginia Clinical Research Conference?

Clinical research saves lives. It takes a lot to bring treatments to patients, and every day and delay affects real people with real families who want to live a longer, better and healthier lives. Every person in the clinical research world plays a critical role in bringing lifesaving medicines to patients who need them.

Health equity expert to speak about efforts to close racial health gaps

Jason Purnell, Ph.D., an associate professor at Washington University in St. Louis, will speak in Richmond as part of National Public Health Week.

A few months before unarmed black teen Michael Brown Jr. was shot to death by a white police officer in the suburban St. Louis town of Ferguson, Jason Purnell, Ph.D., an associate professor at Washington University in St. Louis, published a report on health disparities that found, among other things, that blacks in St. Louis were 17 times more likely to be injured by firearms than their white neighbors.

Purnell’s report, “For the Sake of All: A Report on the Health and Well-Being of African Americans in St. Louis — And Why it Matters for Everyone,” chronicles St. Louis’ persistent racial gaps in education, employment, poverty and mortality. It revealed striking inequalities in St. Louis County, such as the 18-year gap in life expectancy at birth between the predominantly black, low-income neighborhood of Jeff-Vander-Lou and the largely white, affluent suburb of Clayton.

Similar inequalities exist in Richmond. A report published by the Virginia Commonwealth University Center on Society and Health found a 20-year life expectancy gap between the predominantly black Gilpin Court neighborhood and Westover Hills, an affluent mostly white community 5 miles to the west.

“St. Louis and Richmond share some difficult history around issues of race, equity and inclusion,” said Purnell, who will speak in Richmond on April 4 as part of VCU’s participation in National Public Health Week. “Our efforts as a region to address some of these challenges, particularly following the shooting death of Michael Brown, may be instructive for Richmond’s own agenda.”

Purnell will present a talk titled “Advancing Health Equity in St. Louis and Beyond,” at One Capitol Square, 830 E. Main St., from noon to 1 p.m. During his presentation, he will discuss Health Equity Works, a research-based initiative housed in the Brown School of Washington University in St. Louis that specializes in bringing quality, accessible research on health disparities into communities. The organization connects communities with data and provides people with resources, tools and solutions to accelerate action on the many social conditions that influence health and well-being.

Health Equity Works started as a result of Purnell’s report and evolved to include community engagement to address the report’s recommendations.

“Health Equity Works translates data into action to advance community health,” Purnell said. “We partner with a diverse set of community stakeholders to conduct and present research in accessible ways that can inform practice and policy.”

At his April 4 presentation, Purnell hopes to inspire students and faculty members to collaborate with community members on research plans.

“Clinical and translational scientists who want their research to be better connected to the community will need to leave their offices in order to do so,” he said. “Often, this requires showing up and becoming a ‘known quantity’ in the community, offering to help solve problems that may not be connected to one’s current research project. Building upon a foundation of trust will help to identify areas where community needs intersect with scientific inquiry.”

VCU’s participation in National Public Health Week is co-sponsored by the C. Kenneth and Dianne Wright Center for Clinical and Translational Research, the VCU Division of Epidemiology at VCU School of Medicine’s Department of Family Medicine and Population Health and the VCU Center on Society and Health. The week includes presentations by Virginia Department of Health leadership and United Network for Organ Sharing representatives.