VCU and VSU researchers are studying marijuana use and the immune system

Dr. Keen (sitting) and Dr. Abbate (standing) pose for a photo in a laboratory
Larry Keen, Ph.D., and Antonio Abbate, M.D., Ph.D., in the lab. (Photo by Tom Kojcsich, University Marketing)

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

While working with HIV-positive patients at an infectious diseases clinic in Jacksonville, Florida, Larry Keen, Ph.D., met many people who used marijuana to treat pain. “They would roll a joint while on pain medication,” Keen said. “I was like, ‘You never worry about how the marijuana and pain meds are interacting?’ And they looked at me and were like, ‘Why?’”

The question seemed obvious to Keen, who was at the University of Florida on a postdoctoral fellowship funded by the National Institute on Drug Abuse. His research on immune function and neuropsychological performance among people in the African American community often converged toward a widely used but scarcely researched substance — marijuana.

“The study of marijuana use is still burgeoning, which is weird to me because it has been around for thousands of years,” he said.

After completing the fellowship, Keen joined Virginia State University in 2014 as an assistant professor of neuropsychology and psychoneuroimmunology, which is the study of the interaction between psychological processes and the body’s nervous and immune systems. He continued the marijuana research while leading the Psychoneuroimmunology of Risk and Disease Laboratory, where he noticed an association between marijuana use with leukocyte activity and cytokine production in the human body. Both parts of the immune system, leukocytes are white blood cells that help the body fight disease and cytokines are small proteins released by immune cells to help them communicate with one another. Keen found that both played a role in systemic inflammation, but the exact relationship between marijuana use and the immune system markers was not clear.

Energized by his small discoveries and eager to learn more, about two years into his tenure at VSU Keen started to apply for grant funding to explore further his area of research. However, much of the feedback he received took on a familiar tone.

“I got reviews back saying, ‘The guy is kind of cool, but he doesn’t have the resources at his university to carry the work out,’” he said. “They told me I needed collaborators, so I took that to heart and I started looking.”

Knowing that a major research university was just 30 miles north of the VSU campus, Keen started his search for collaborators on Virginia Commonwealth University’s website. “There was no one at VSU who was doing anything close to what I was doing with substance use, immune function and cognition,” he said. “I needed mentorship.”

Dr. Keen works in the laboratory while Dr. Abbate observes.
Abbate and Keen hope their partnership — created by an NIH grant — paves the way for further collaboration between VCU and VSU. (Photo by Tom Kojcsich, University Marketing)

Browsing through VCU faculty profiles, Keen found cardiology professor Antonio Abbate, M.D., Ph.D. Among other things, Abbate researches inflammation. Keen emailed and to his surprise, Abbate responded, inviting Keen to a meeting at the VCU C. Kenneth and Dianne Wright Center for Clinical and Translational Research. The meeting focused on developing strategies for recruiting participants to a community-based substance-use disorder study.

“That was something I could help with,” Keen said.

A mentoring relationship soon developed between Abbate and Keen. Abbate, an associate director of the Wright Center, takes a special interest in mentoring students and junior faculty members. In February, he was presented with the inaugural Thames-Kontos Mentoring Award from the VCU School of Medicine and in May, he was given the VCU Undergraduate Research Opportunities Program Faculty Mentor Award. In 2016, the School of Medicine honored him with the Distinguished Mentor Award.

“He took an interest in mentoring me and was like, ‘What do we need to do to get you where you want to go?” Keen said.

The pair continued to collaborate and in late 2018 Abbate suggested that Keen apply for a Research Supplement to Promote Diversity in Health-Related Research, which was awarded to the Wright Center by the National Institutes of Health’s National Center for Advancing Translational Sciences. The Wright Center is eligible for the supplement as a member of the Clinical and Translational Science Awards Program, a national consortium of more than 50 research institutions that are accelerating the transformation of laboratory discoveries into treatments for patients.

“We mapped it out, bounced a couple ideas around for maybe a week, and then we started writing and that was it,” Keen said.

Keen was awarded the research supplement in May, enabling him to devote 75 percent of his time to training and research activities for two years.

“I have been at VSU for five years now and I am building my own thing there, but the research supplement gives me an opportunity to expand my expertise,” he said.

The supplement supports a pilot study that Keen will lead investigating the complex interplay among marijuana use, brain activity and the immune system. “This is the first pilot study I will be able to do where I can look at a complete picture of how chronic marijuana use affects a variety of bodily systems, including leukocyte and cytokine activity,” he said.

Dr. Keen (left) talks with Dr. Abbate (right) in the lab.
Keen, left, will lead an investigation into the complex interplay among marijuana use, brain activity and the immune system. “This is the first pilot study I will be able to do where I can look at a complete picture of how chronic marijuana use affects a variety of bodily systems,” he said. (Photo by Tom Kojcsich, University Marketing)

Keen will conduct research at the Wright Center’s Collaborative Advanced Research Imaging facility with a sample of 50 people who live in the Richmond metropolitan area, half of whom have marijuana use disorder. In addition to working with faculty members and students from the MCV and Monroe Park campuses, Keen will enlist VSU graduate and undergraduate students to help with the research.

“Being able to partner with VCU in this way gives my students exposure to lab work and MRI research,” he said, adding that he hopes the partnership paves the way for further collaboration between the two institutions.

The supplement also provides Keen with opportunities to expand his expertise through coursework and career development activities. Over the next four semesters, Keen will enroll in VCU courses on topics including immunobiology, scientific integrity and responsible scientific conduct. He also will attend monthly Wright Center Clinical Research KL2 Scholar meetings.

He hopes the training program prepares him to be more of an independent investigator.

“This work is building me to the point where the NIH and other agencies will see me as an expert and will fund my research,” Keen said. “In order for me to be an independent investigator, I need to pay my dues. I need to publish, work on smaller developmental grants, and build a collaborative network that shows that I am supported. It is funny how having more of a team makes you more independent.”

Wright Center welcomes three inaugural C. Kenneth and Dianne Wright Physician-Scientist Scholars

Dr. Buckley stands smiling with the three scholars and Mr. Wright in a ballroom. All are wearing suits.
From left to right: VCU School of Medicine dean Peter Buckley, M.D., Teja Devarakonda, Graeme Murray, Mr. Ken Wright, and Eric Kwong

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

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.

Wright gift enables researchers to find answers in data

Mr. Wright stands with Dr. Moeller. Mr. Wright is wearing a tweed jacket and red collared shirt. Dr. Moeller is wearing a white dress shirt and light blue tie.
Mr. Ken Wright stands with F. Gerard “Gerry” Moeller, M.D., at the new 6,000-square-foot research space dedicated to biomedical informatics at VCU. The Wright Center Biomedical Informatics Program has expanded over the past year to enable researchers to explore diseases and treatments in new ways. Photo by Eric Peters

This story originally appeared in the MCV Foundation‘s Chronicle of Giving magazine. To read the full story and other articles about the life-saving effect of private gifts on the MCV Campus, click here

Thanks to a $5 million gift last spring from one of Virginia Commonwealth University’s most generous supporters, biomedical informatics at the C. Kenneth and Dianne Wright Center for Clinical and Translational Research is poised to change the way research in our region can be conducted.

Ken Wright’s gift established a new 6,000-square-foot space where more than a dozen specialists serve the community’s and the university’s research needs. With the help of biomedical informatics, researchers can combine large amounts of data, such as imaging and genomic information, to find answers that lead to preventions or new treatments for diseases.

One example of how biomedical informatics can work is in screening for mild traumatic brain injury. Mild traumatic brain injury doesn’t have a very strong signal if a radiologist looks at an MRI alone, but combining the data from that MRI with other available data could be very beneficial. For example, a care team could search for the previously unnoticed and small mild traumatic brain injury signatures that appear every time in millions of data points beyond just MRIs.

F. Gerard “Gerry” Moeller, M.D., is the director of the Wright Center, associate vice president for clinical research and the inaugural C. Kenneth and Dianne Wright Distinguished Chair in Clinical and Translational Research. He is using biomedical informatics to make an impact in his own research as he studies the effectiveness of initiating long-term recovery care for opioid overdose
survivors before those survivors ever leave the emergency department. By providing a medication earlier than current practices dictate, and by providing a same-day referral to a recovery facility, Dr. Moeller expects to reduce repeat overdoses and deaths.

The impact Mr. Wright’s giving has made on the research infrastructure at the university and the center bearing his name played a critical role in helping the center secure the largest National Institutes of Health grant in the university’s history. Announced in May 2018, the $21.5 million award will support the Wright Center in its mission to advance university and community research from basic laboratory science to treatments that improve human health.

“Last year’s grant and Mr. Wright’s most recent gift are going to dramatically enhance our biomedical informatics capabilities,” Dr. Moeller said. “We’re expanding into those areas where there are really massive amounts of data so we can look at diseases in ways we haven’t been able to do before.”

If you’re interested in learning about the tools available to support the Wright Center, patient care, research or education across the MCV Campus, contact Brian Thomas at brian.thomas@vcuhealth.org or 804-828-0067.

Wright Center students and staff work with Massey researchers to develop first comprehensive models of “seeds and soil” as a means to combat breast cancer metastasis

Dr. Chuck Harrell and Tia Turner stand in a laboratory side-by-side. Both wearing white lab coats.
From left to right: Chuck Harrell, Ph.D., and Wright Center M.D.-Ph.D. student Tia Turner (Photo by Craig Hutson Photography)

With support from the VCU Wright Center, scientists at VCU Massey Cancer Center have identified key biological pathways that regulate the spread of tumor cells to vital organs. These findings may have a significant influence on the development of new therapies that slow or prevent breast cancer metastasis.

Metastasis refers to the spread of cancer cells to other organs, and the likelihood of curing cancer is significantly reduced once the disease has spread. Nearly all breast cancer deaths are caused by metastasis within vital organs.

The concept of cancer metastasis has long been supported by the “seed and soil” proposal, in which it is theorized that cancer cells (seeds) are dependent upon the tissue of organs (soil) to thrive in sites beyond their point of origin. This hypothesis laid the foundation for why cancer metastases are more common in certain organs over others, such as the lungs, lymph nodes, bones or liver. The idea is that these organs offer a more fertile environment for cancer cell growth. Since this proposal’s inception over a century ago, much more emphasis has been placed on studying the seeds rather than the soil. Scientists have focused heavily on the genetic properties of cancer cells that have spread to other organs, but what have remained much less understood are the genomic properties of the organic tissue that harbors successful metastatic growth.

Research led by Chuck Harrell, Ph.D., member of the Cancer Molecular Genetics research program at Massey and assistant professor of pathology at the VCU School of Medicine, set out to better understand the cancer-specific and organ-specific genomic qualities that contribute to successful breast cancer metastasis.

Using mouse models containing cells from breast cancer patients, Harrell developed novel metastasis representations of different types of breast tumors found in humans. Wright Center clinical and translational sciences M.D.-Ph.D. student Tia Turner helped develop and characterize the models.

“These are the first models that characterize how cancer cells genetically change when they have spread to different organs, and, in parallel, that demonstrate how the organ genetically responds to the invading cancer cells,” Harrell said.

In the study, published in Breast Cancer Research, Turner worked with Harrell and a team of researchers to create RNA sequencing datasets for metastatic models of ER-positive, triple negative and HER-2 positive breast cancer, with a particular focus on triple negative breast cancer due to the lack of current treatment options available. As part of the research team, Turner performed RNA preparations from tumors and metastases for RNA-sequencing, as well as in vitro testing of SRC inhibitors on cancer cells.

“We discovered that during the growth of breast cancer metastases, genomic changes occurred within both the cancer cells and the organ microenvironment,” Harrell said. “Our experiments identified key biological pathways that control the growth of breast cancer metastases, and we believe these findings can be used to help develop targeted therapeutics that prevent or slow cancer progression.”

Specifically, the researchers identified the SRC signaling pathway as highly activated in breast cancer metastases. This pathway plays a role in cell growth and embryonic development, and it impacts other pathways to promote blood vessel formation, cell survival and proliferation. However, drugs that inhibit the SRC pathway have already been developed and were proven clinically ineffective as a sole method of cancer therapy, often leading to continued tumor growth.

“Multiple pathways within the cancer cells, and potentially within the host organ as well, may need to be targeted to inhibit the growth of metastases,” Harrell said. “Our ongoing efforts are aimed at identifying synergistic combinations of drugs that inhibit the SRC pathway and other pathways that promote metastasis.”

Photo of Amy Olex smiling wearing a red short-sleeved blouse and square-rimmed glasses
Amy Olex

Wright Center senior bioinformatics specialist Amy Olex played a central role in the bioinformatics analysis of the genomics data, helping to develop and implement a bioinformatics pipeline to process the RNA-sequencing dataset from the samples that Harrell’s team generated. “This pipeline had to be able to separate human and mouse genomic material so that we could analyze human tumor and mouse microenviroment gene expression individually for each mouse model,” Olex said, adding that the separation of human and mouse genomic material was done digitally, so no wet lab techniques were needed to physically sort out human and mouse tissue prior to sequencing.

Turner continuously uses the RNA-sequencing dataset that Olex helped develop to investigate other potential drug targets in mammary tumors and metastases. “The dataset is an extremely valuable resource in our ongoing search for important pathways in breast cancer metastases, as well as the organs bearing those metastases, that may serve as promising drug targets,” Turner said.

Harrell, Turner and the research team conducted a second related study, which focused on the characterization of how 14 different patients’ breast cancer cells grew when they had spread to the liver. Turner helped prepare mouse model tumor tissues for the liver metastasis experiments.

“We were able to determine that the breast cancer cells grew at varying rates and many were structurally distinct as liver metastases,” Harrell said. “Evaluating the diversity of presentation within metastatic disease is essential to developing novel targeted therapies.”

Harrell observed a correlation between increased spread of tumor cells and a greater influx of innate immune cells, which are the body’s automatic first line of defense against disease. This finding warrants further investigation of innate immune cell interaction with breast cancer liver metastases and the liver microenvironment.

Harrell said this research is important because scientists need reliable metastasis models to use in order to determine the drugs that can be an effective alternative for treating surgically inaccessible cancer cells.

For Turner, the research experience is contributing to her efforts toward identifying novel combination therapies for triple-negative breast cancer. “The Wright Center has contributed greatly to my work,” she said. “As a M.D.-Ph.D. student in the cancer and molecular medicine program, my training has been focused heavily on the integration of basic and clinical sciences, with a strong emphasis on translational research fostered by the Clinical and Translational Science Award.” The interdisciplinary training program has helped Turner integrate her clinical knowledge into research, “which is highly important in preclinical drug development studies aiming for successful translation into the clinical setting and advancements in patient care,” she said. “My training through the Wright Center has helped me develop the skills and perspective needed in carrying out translational research.”

Harrell, Olex and Turner collaborated on these research efforts with Mikhail Dozmorov, Ph.D., member of the Cancer Molecular Genetics research program at VCU Massey Cancer Center; Mohammad Alzubi, Sahib Sohal,  Madhumitha Sriram, Patricija Zot and Michael Idowu of the VCU Department of Pathology at VCU School of Medicine; Jonas Bergh, M.D., Ph.D., Thomas Hatschek, M.D., Ph.D., and Nicholas Tobin, Ph.D., of Cancer Center Karolinska in Sweden; Joel Parker, Ph.D., Charles Perou, Ph.D., and Susana Recio, Ph.D., of UNC Lineberger Comprehensive Cancer Center; and Carol Sartorious, Ph.D., of the University of Colorado.

This research was supported, in part, by METAvivor; the National Cancer Institute (P50-CA58223, R01-CA148761 and R01-CA195754); the Breast Cancer Research Foundation; the National Center for Advancing Translational Sciences (CTSA award No. UL1TR002649); and, in part, with funding from Massey’s NIH/NCI Cancer Center Support Grant P30 CA016059.

Re-purposed from an article by Blake Belden, VCU Massey Cancer Center

Community engagement transcends translational science spectrum at annual conference

Dr. Gerry Moeller speaks animatedly wearing a suit in front of a mustard yellow wall
Wright Center Director F. Gerard Moeller, M.D. Photo by Kevin Morley, VCU University Relations.

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

At the Virginia Commonwealth University Community Engagement Institute on May 14, Wright Center Director F. Gerard Moeller, M.D., discussed how he harnesses community-academic partnerships to address the opioid epidemic.

“Virginia has succumbed to the opioid overdose epidemic just like the rest of the country, and the patterns vary significantly from one county to the next,” he said. “Dealing effectively with this is going to require a community-engaged approach. We will not have an impact without fostering partnerships with our community.”

The mantra of community members’ fundamental role in impactful translational research echoed throughout the two-day conference held on the VCU Monroe Park Campus, where more than 80 community-engaged scholars gathered to explore the power and potential of university-community partnerships.

“The Community Engagement Institute provided us with an opportunity to connect and re-establish existing connections with people who are energized about continuously improving our community engagement efforts,” said Wright Center community engagement associate Alicia Aroche, who helped plan the conference and presented on best practices for communicating about the work of community-academic partnerships.

Since May 2014, the Wright Center and the VCU Division of Community Engagement have partnered annually to host the event that unites academic and community stakeholders who share a commitment to solving challenges through community-academic collaboration. “When you have complex problems, it takes people with varying expertise from the community and academic centers to solve them,” said VCU Division of Community Engagement vice provost Cathy Howard, Ph.D. Through interactive workshops, attendees built skills around initiating and sustaining community-academic partnerships, as well as assessing and communicating the work of such partnerships.

“Partnering with our communities allows us to do better research,” said Wright Center community-engaged research co-director Alex Krist, M.D.

The three Wright Center Clinical Research KL2 Scholars smile for a photo. They are all wearing cardigans.
Wright Center Clinical Research KL2 Scholars (from left to right) Guizhi (Julian) Zhu, Ph.D.; Mario Acunzo, M.D.; and Elizabeth Wolf, M.D. Photo by Kevin Morley, VCU University Relations.

Krist is a mentor to Wright Center Clinical Research KL2 Scholar Elizabeth Wolf, M.D., who is working on a community-engagement project that aims to identify geographic and patient-level risk factors for inadequate prenatal and well-child care in the Greater Richmond Region. “I attended the Community Engagement Institute because I wanted to learn more about best principles that I could apply to my research,” Wolf said. The assistant professor of pediatrics and emergency care at VCU School of Medicine is partnering with the VCU Center on Society and Health’s Engaging Richmond program to develop strategies aimed at reducing health disparities for vulnerable women and children.

The conference was funded in-part through the $21.5 million Clinical and Translational Science Award that the Wright Center received from the National Institutes of Health in 2018. The largest NIH grant in VCU’s history allows the Wright Center to collaborate across disciplines within the university and health system, and with community partners around the region, all with the shared goal of accelerating innovative research that advances the scientific study of human health.

“Events like the annual Community Engagement Institute allow us to better mobilize existing strengths in community engagement and team science to engage stakeholder communities at every translational phase,” Krist said. “Ultimately, we want to work with community members as research partners and form collaborative clinical research translational science teams to improve the health of our communities together.”

Second Opportunities for Lasting Change

Dr. Moeller stands with his arms crossed in front of the VCU Medical Center Emergency Department entrance. He is wearing a white lab coat.
Wright Center Director F. Gerard Moeller, M.D., is the principal investigator on a clinical trial that is initiating long-term care for opioid overdose survivors inside emergency departments. Photo: Kevin Schindler

This story originally appeared in the MCV Foundation‘s Next magazine. To read the full story and other articles about life-changing innovations occurring on the MCV Campus, click here

Those who survive an opioid overdose usually do so because they’re found in varying states of consciousness by family members, friends, caregivers or first responders before their breathing stops completely.

These survivors gain an additional opportunity at life, but oftentimes, because of the nature of their illness, they can’t use their new opportunities for change and recovery.

F. Gerard “Gerry” Moeller, M.D., director of the VCU C. Kenneth and Dianne Wright Center for Clinical and Translational Research, began contemplating these missed opportunities one day in 2017 after hearing from colleagues in the VCU Health Emergency Department.

“They came to me and said they were seeing overdose patients time and time again, and they felt like they just weren’t accomplishing anything,” Dr. Moeller said. “They were reviving the patients, but then the survivors weren’t getting into long-term treatment.”

Dr. Moeller, who is internationally known for his translational research on impulsivity and addictions, is keenly aware of the importance long-term treatment plays in pulling people out of a deadly spiral like the one his colleagues described to him, and he wanted to help.

His preliminary data showed that opioid overdose visits to the VCU Health Emergency Department went from approximately 270 in 2015 to more than 650 in 2017, and from all of those visits, as many as one in five patients experienced a repeat overdose or died within 12 months of their initial overdose.

Dr. Moeller knew these numbers demanded action toward finding the reason survivors weren’t getting the help they needed, and, most importantly, toward identifying a new approach to helping the survivors avail the opportunities they’d been given for a new life.

Why are survivors not getting help?

After an overdose victim arrives at the emergency department, he or she is stabilized, monitored for some time and then referred to a long-term outpatient facility where appropriate follow-up treatment, usually for addiction, can begin.

Dr. Moeller believes this referral is the critical moment in the treatment paradigm that can and should be changed. That’s because the overdose medication naloxone is very effective at saving lives, but it also causes acute opioid withdrawal, leading to nausea, vomiting, sweating, diarrhea, chills, cravings, impulsivity and poor decision-making.

“One of the behavioral definitions of impulsivity is the lack of ability to delay your gratification,” Dr. Moeller said. “So, if you’re in withdrawal, you have all these symptoms and you wish you were dead. You realize that when you walk out the door of the hospital you can get something that will make you feel better — it’s heroin, or it’s oxycodone, or it’s a pill. Even though you know you just almost died from an overdose, the threat of that happening again is in the future.”

Because of this impulsivity, which is often amplified because of the lifesaving medication, many patients never go to clinics when they’re referred for long-term treatment, opting instead to seek an immediate fix.

What can be changed to better encourage long-term care?

Instead of referring overdose survivors, who are likely experiencing acute withdrawal, to long-term care after they leave the emergency department, Dr. Moeller is testing the effectiveness of initiating long-term treatment before the survivors ever leave the hospital. The goal here is to counteract withdrawal symptoms and reduce impulsivity.

For those who agree to participate, Dr. Moeller’s team, working inside the emergency department, makes contact and provides a medication called buprenorphine that reverses the withdrawal symptoms. Patients are then given a referral within 72 hours to the outpatient clinic, where they continue medication and counseling for addictions.

In addition to administering buprenorphine as early as possible before survivors leave the hospital, the long-term care component of the study is vitally important to the recovery of survivors. In Richmond, referrals to long-term outpatient care guide participants to the VCU Health MOTIVATE Clinic, where social workers, nurses and physicians monitor patients’ progress weekly, provide behavioral counseling sessions in individual and group settings, and administer buprenorphine monthly.

Improving the likelihood that overdose victims reach this long-term component of care is essential, Dr. Moeller said. “Addiction really is a chronic medical disorder. Like diabetes and hypertension, a one-time treatment is not going to solve the problem, so patients need chronic medication and behavioral treatments like group therapy to help them with lifestyle changes.”

Dr. Moeller will serve as principal investigator on the trial and will work with Robert Lipsky, Ph.D., director of translational research in the Department of Neurosciences at Inova Fairfax Hospital, and Warren Bickel, Ph.D., professor of psychiatry and director of the Addiction Recovery Research Center at Virginia Tech Carilion Research Institute. The trial is funded in part by a $500,000 Virginia Catalyst grant from the Virginia Biosciences Health Research Corporation.

If the results show what Dr. Moeller expects, which is a significant drop in repeat overdose and death rates compared to previous data, this trial will establish a new paradigm for treatment of patients after opioid overdose that can be utilized nationally to help survivors get the help they need before it’s too late.

The MCV Foundation encourages and stewards gifts to support research like Dr. Moeller’s that fight all types of diseases. If you’re interested in learning about the tools the Foundation has available to use in making those gifts, visit their giving page.

Wright Center hosts Mentorship Academy aimed at creating a culture of mentorship at VCU

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

Dr. Nana-Sinkam points behind him to a screen with an infographic describing training opportunities
Wright Center KL2 program co-director Patrick Nana-Sinkam, M.D., presented on training and mentorship opportunities at the Wright Center during the 2019 Mentorship Academy. Photo by Allen Jones, VCU University Relations

At the Wright Center Mentorship Academy on May 3, nearly 50 faculty researchers from eight schools and colleges across the Virginia Commonwealth University MCV and Monroe Park Campuses gathered to discuss mentorship best practices.

“We set out to identify leadership from across the university to attend the Mentorship Academy, with the ultimate goal of using this as a starting point from which to foster a culture of mentorship at VCU,” said Wright Center KL2 program co-director Patrick Nana-Sinkam, M.D. The VCU School of Medicine professor and division chair organized the daylong conference at which attendees discussed ways to create and nurture a culture of mentorship within their schools, colleges and departments.

The workshop was facilitated by the Center for Improvement of Mentored Experiences in Research, which is a nationally recognized leader in providing mentoring and training resources. The evidence-based program was developed at the University of Wisconsin-Madison to help mentors develop skills for engaging in productive, culturally responsive research mentoring relationships that optimize the success of mentors and mentees. “We are here to help VCU faculty promote their own mentoring initiatives by thinking strategically about their mentoring practices and leveraging the experiences of their colleagues to learn from one another,” said program facilitator Kelly Diggs-Andrews, Ph.D.

Throughout the day, VCU faculty members learned skills and developed tools to help them build, increase and improve departmental mentorship infrastructure. “The culture of mentoring is complex,” said Gregory Triplett, Ph.D. The associate dean for graduate studies and research at the VCU College of Engineering attended hoping to learn mentoring strategies that he could bring back to his colleagues. “Workshops such as this provide important details for frameworks that we can further expand upon at our individual units,” he said.

While previous Mentorship Academies hosted by the Wright Center have included mostly trainees and junior faculty members, the 2019 event was targeted toward senior-level faculty members to try to increase institutional support for building a culture of mentorship at VCU. Attendees included 25 professors from VCU Schools of Medicine, Dentistry, Nursing, and Pharmacy, as well as the VCU Colleges of Engineering, Humanities and Sciences, and Health Professions, and VCU Life Sciences. Also in attendance were three School of Medicine department chairs, three members of the VCU Vice President for Research and Innovation’s Research Development Advisory Council, the School of Medicine’s associate chair for faculty development and the VCU senior vice provost for faculty affairs.

“In order to achieve our goal of fostering a culture of mentorship throughout VCU and VCU Health, we need buy in from senior leadership,” Nana-Sinkam said. “We want to help create a sustainable pool of senior faculty mentors and incentivize those mentors to create a community.”

A pyramid-shaped infographic describing mentorship and training opportunities available at the Wright Center
Wright Center training opportunities include mock study sections, grant writing seminars and biostatistics assistance.

The day included presentations and facilitated discussions on topics including maintaining effective communication, aligning expectations between mentors and mentees, addressing equity and inclusion, and promoting professional development and work-life integration.

In the afternoon, Nana-Sinkam and Wright Center Director F. Gerard Moeller, M.D., presented on training opportunities within the Wright Center, including grant writing seminars, mock study sections, and assistance with bioinformatics and biostatistics. They highlighted the Wright Center’s newest program, Faculty Mentor Office Hours, where early career faculty can sign-up to meet with senior faculty mentors and discuss topics ranging from promotion and tenure to professional development and grant applications. They also discussed several research training programs administered by the Wright Center, including the Emerging Scholars program, Translational Science Scholars program and KL2 Program, which provide early career researchers with the opportunity to participate in mentored research and career development activities. They ended the presentation with a review of the research supplements that are provided by the Wright Center through the National Institutes of Health to promote diversity and re-entry into biomedical and health-related research professions.

“There is a huge need for leadership in the biomedical research space,” said Moeller, adding that the Wright Center programs he presented on are intended to address that shortage. “We need mentors who are equipped to train the next generation of researchers because without mentorship, junior faculty are not going to succeed.”

The program was made possible through the $21.5 million Clinical and Translational Science Award that the Wright Center received from the NIH in 2018. The largest NIH grant in VCU’s history allows the Wright Center to facilitate collaboration among diverse expertise within the university.

“The Wright Center’s mission is to translate basic science to having an impact on the health of the community and we need translational researchers in the pipeline to carry that mission forward,” Moeller said. “By training a new generation of interdisciplinary clinical and translational scholars, we can work toward ensuring our vision is sustained.”

Wright Center associate director honored for his contributions toward undergraduate mentorship at VCU

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

Photo by Kevin Morley, VCU University Relations.

At a study abroad program in Fondi, a city halfway between Rome and Naples in central Italy, Henrico-native Krishna Ravindra discovered a passion for clinical and translational science. “Working with Dr. Abbate allowed me to see how a background in clinical medicine and translational research can allow one to not only help patients based on the current medicine available, but also have the opportunity to explore novel therapeutic strategies to improve patient care,” Ravindra said of Antonio Abbate, M.D., Ph.D., who leads the Virginia Commonwealth University study abroad trip hosted by the Instituto San Francesco and the University Campus Biomedico of Rome. During the three-week program, undergraduate VCU Honors College students study the signs and symptoms of disease and explore clinical and translational research.

 

When they returned to Richmond in the fall of 2017, Ravindra asked Abbate if he could shadow him during his clinical rotations at VCU Medical Center and volunteer on Abbate’s research team. Abbate, who is an associate director at the VCU C. Kenneth and Dianne Wright Center for Clinical and Translational Research, serves as the James C. Roberts, Esq. Professor of Cardiology at the VCU School of Medicine, as well as a practicing cardiologist at the VCU Health Pauley Heart Center and medical director at the VCU Medical Center Clinical Research Unit. “I am always happy to open my research team to undergraduate students,” Abbate said, adding that he became involved in research when he was 20 years old and benefitted from working with mentors who shared their enthusiasm for medical discovery and innovation early in his career. “It is important to offer students an opportunity to see what gets you up in the morning,” he said.

 

In the ensuing years Ravindra continued to volunteer on research projects under Abbate’s mentorship, including working with Abbate through the VCU Undergraduate Research Opportunities Program. On April 24 Abbate was recognized for his work through that program with the VCU Undergraduate Research Opportunities Program Faculty Mentor Award, an honor that recognizes faculty members who have demonstrated a commitment to regularly go above and beyond to engage undergraduate students in research opportunities.

 

“Dr. Abbate placed an enormous amount of faith in me as an undergraduate student to complete complex chart reviews, patient analyses, and retrospective data analyses,” Ravindra said.

 

Through UROP, Ravindra worked with Abbate on a retrospective analysis of patients who were treated at VCU Medical Center for Takotsubo cardiomyopathy, a complex clinical condition in which a person suddenly develops heart failure after emotional or physical stressors. Ravindra also worked on another research project aimed to predict the degree of cardiorespiratory fitness impairment in heart failure patients across a wide range of ejection fraction measurements, which indicate how much blood the left heart ventricle pumps with each contraction.

 

For four months Ravindra worked with Jessie van Wezenbeek, a graduate student from Amsterdam, on data collection and statistical analysis, which informed a manuscript detailing their findings. The manuscript published in the peer-reviewed journal Frontiers in Cardiovascular Medicine late last year and in November Ravindra presented the results of the pair’s research projects at the American Heart Association Scientific Sessions conference in Chicago.

 

“I would never have dreamed of getting to present at such a large conference as an undergraduate student before working with Dr. Abbate,” Ravindra said. “Working with Dr. Abbate opened that door for me, as he constantly pushed me out of my comfort zone and took time to teach me one-on-one.”

 

Ravindra said Abbate inspired him to pursue a career in clinical and translational science. In the fall he will start medical school at VCU. “Dr. Abbate has shaped my view of what it means to be a physician and has illuminated the benefits of being a physician-scientist,” he said. “He emphasized the bench-to-bedside process of clinical and translational research. Further, he showed me that the process of discovery is never-ending and that we can always strive to do more for our patients.”

 

Abbate has devoted a significant amount of effort toward training the next generation of clinical and translational scholars since joining VCU in 2007. In 2016, the School of Medicine awarded him with the Distinguished Mentor Award, an honor that recognizes significant contributions to the career development of others.  In February, he was awarded the inaugural Thames-Kontos Mentoring Award from the VCU School of Medicine Department of Internal Medicine.

 

The Wright Center has funded two faculty-mentored undergraduate clinical and translational research projects through UROP every year since 2014. This summer, the Wright Center will fund biomedical engineering student Yasmina Zeineddine to research spinal cord injuries with mentor Carrie Peterson, Ph.D., who is an assistant professor in the Department of Biomedical Engineering at VCU College of Engineering. The Wright Center will also fund mechanical engineering student Sam Cole’s research on bioreactors for mechanical training of engineered tissues with mentor Joao Soares, Ph.D., who is an assistant professor at the VCU College of Engineering.

 

“The Wright Center is committed to fostering cross-campus collaborations with the VCU College of Engineering and other units on the VCU Monroe Park Campus with an aim of developing an interdisciplinary clinical and translational workforce that will be equipped to address emerging health care challenges,” said Wright Center Director F. Gerard Moeller, M.D. “We are happy to partner with the VCU Undergraduate Research Opportunities Program to help inspire an early interest in clinical and translational research among undergraduate researchers.”

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.

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

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.