Zero to Sixty: The Wright Center’s rapid response to COVID-19

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.

Arun Sanyal, M.D.

By late March, Wright Center Associate Director Arun Sanyal, M.D., had partnered with Gilead to bring remdesivir treatment trials to VCU. And on May 1, armed with data that VCU’s trial helped provide, the FDA issued emergency authorized use of the drug.

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:

F. Gerard Moeller, M.D.
  • 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.

Antonio Abbate, M.D., Ph.D.

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.

The Wright Center’s informatics team, under the leadership of Tamas Gal, Ph.D., MBA, which helps compile and analyze clinical data, has re-oriented their programming projects toward registries, surveys, portals and application processes, like a survey for those who might’ve noticed a change in their smell or taste abilities – one of the virus’ symptoms.

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.

3D printed ventilator
The 3D-printed ventilator created by an interdisciplinary team connected by the Wright Center. (Photo courtesy of Trevor Beck Frost)

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.

OVPRI, in collaboration with the Wright Center, is foregoing certain typical licensing fees during the pandemic in order to facilitate the research and development that will help combat COVID-19 collaboratively.

Annual Clinical Trials Day took on a new meaning this year, as the community rallied around healthcare providers. A COVID-19 patient in a trial run by Abbate told her story, and Abbate, Joan Greer, and Lauren Harris discussed clinical trials for a public audience.

Similarly, Wright Center researchers have acted as experts for media outlets – providing a crucial science-based perspective for the community during this public health crisis. Among others:

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.

Many studies have adapted using telehealth technologies that Wright Center has led the way in. Richard Sterling, M.D., whose research has been heavily supported by the Wright Center, spoke to VCU News about telehealth in the time of a pandemic, as doctors and patients sought alternatives to in-person visits and checkups.

Suffice it to say, the Wright Center has made VCU’s rapid response to COVID-19 possible – in more ways than one.

WATCH: Antonio Abbate and Joan Greer in conversation with Lauren Harris for Clinical Trials Day

Lauren Harris, Wright Center’s hub research capacity administrator, interviews Antonio Abbate, M.D., Ph.D., the medical director of the Clinical Research Unit and an associate director at the Wright Center, and Joan Greer, R.N., nurse manager at the Clinical Research Unit at VCU Health.

Abbate and Greer answer your questions about clinical trials participation and what it’s like running clinical trials during a pandemic – in honor of Clinical Trials Day on May 20.

 

Full transcription below:

Lauren Harris (00:06):

Good afternoon. Thank you all for taking the time out of your day to come and speak with me this morning about clinical trials. As we all know, and the world may also know, that international clinical trials day is coming up on May the 20th. This is truly a time for us to thank our clinical research, trial coordinators, our nurses, our doctors, anyone who helps in getting clinical trials off the ground. International Clinical Trials will be celebrated across the world, not only from VCU and VCU Health, but across the globe. We will all be telling you thank you for your hard work and your dedication that you all put into this. Surrounding this, this day allows us also to broadcast some of the clinical trials that we have going on here at VCU and VCU Health. So today with me, I have. Dr. Antonio Abbate who is the director of the clinical research unit here at VCU Health and Joan Greer, who is the nurse manager on the North 8 floor for the Clinical Research Unit. Thank you guys. Read More

A taste of Italy: Professor’s clinical research examines whether food really is the best medicine

Selection of healthy fat sources. Top view.

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

Virginia Commonwealth University assistant professor Salvatore Carbone, Ph.D., smiles as he fondly recalls dinners with his family during summers spent in Sperlonga, Italy, a coastal town overlooking the Mediterranean Sea.

“Extra-virgin olive oil was on everything, from pasta to fish and vegetables,” he said.

The Italy native joined VCU to study under Antonio Abbate, M.D., Ph.D., soon after completing degrees in dietetics and nutrition in his home country. As a research nutritionist at the VCU Health Pauley Heart Center, Carbone routinely saw patients who suffered from obesity and heart disease. He wondered how diet contributed to their health conditions.

“Most people in Italy follow a mostly Mediterranean diet, which is rich in unsaturated fat,” Carbone said, referring to the nutrients sometimes called “healthy fats” that are found in foods such as extra-virgin olive oil, nuts and avocado. “In the U.S., there is a trend of promoting a low-fat diet to prevent cardiovascular diseases, but in Mediterranean countries, where the risk of developing things like heart disease and diabetes is significantly lower, the diet tends to be high in healthy fat. I thought, ‘Why can’t we try that in the U.S.?’”Headshot of Salvatore Carbone

The thought sparked a series of preclinical and clinical research studies. Through these studies, Carbone attempted to determine if a diet rich in healthy fats that resembled the Mediterranean dietary pattern could improve body composition, cardiac function and, ultimately, exercise capacity in people who were obese and had a specific form of heart failure called heart failure with preserved ejection fraction.

Also known as HFpEF, heart failure with preserved ejection fraction occurs when the heart pumps blood and contracts normally, but is too stiff to fill and relax properly. About 5.7 million adults in the U.S. have heart failure, according to the Centers for Disease Control and Prevention, and about half of those people present with HFpEF. In the U.S., more than 80 percent of people who have HFpEF are overweight or obese.

“There is an urgent medical need for therapy,” Carbone said, adding that no Food and Drug Administration-approved therapies exist for people who have obesity and HFpEF. “Often, we think about pharmacologic approaches, but drugs often only target one thing. With the dietary intervention we are proposing, we hope to target multiple risk factors to eventually improve health outcomes.”

In August, the VCU C. Kenneth and Dianne Wright Center for Clinical and Translational Research awarded Carbone with a Clinical Research Voucher to support his work. The Clinical Research Voucher Program was established this year to increase use of the VCU Medical Center Clinical Research Unit, a 10,000-square-foot space on the eighth floor of VCU Medical Center’s North Hospital that provides VCU Health clinicians with the physical space and support necessary to conduct clinical research. Vouchers are the equivalent of up to $10,000 in VCU Health services for research.

“The Wright Center has been extremely helpful,” Carbone said. “Just having the space and time available at the Clinical Research Unit, as well as people trained in research, helps us immensely.”

Antique world map Mediterranean

From observation to action 

Soon after observing differences between the foods he grew up eating and the typical American diet, Carbone launched a preclinical study in 2014. In a laboratory, he fed mice a high-sugar and high-saturated fat diet.

“Simply putting mice on an eating regimen resembling a Western diet impaired their cardiac function even before the mice became obese,” Carbone said of the preclinical study results, adding that he researched the components of an average American eating pattern in scientific journals to create a similar diet for the mice. His findings in the literature were reinforced with what many of the patients with heart disease at VCU Medical Center reported eating: saturated fat from animal-derived products including beef, butter and excess dairy products, and sugar from sweets and sodas.

Around the same time that Carbone concluded the preclinical research, Abbate and VCU School of Pharmacy professor Benjamin Van Tassell, Pharm.D., were leading a large clinical trial studying patients who had HFpEF. They allowed Carbone to interview 23 of their patients about their diet. Through the interviews, he found that patients who consumed more healthy fats had better exercise capacity, which was measured as peak oxygen consumption during a cardiopulmonary exercise test, than those who didn’t. He also found that increased consumption of healthy fat was associated with improved cardiac function and better body composition.

“Based on that study, we knew we had a promising association, but association doesn’t mean causation,” Carbone said.

Rather than testing his theory on human subjects right away, Carbone went back to the lab. This time, he fed mice two different diets with the same amount of calories and total fats — one high in saturated fat and low in healthy fats, and one low in saturated fat and high in healthy fat.

“Within eight weeks, which is the equivalent of several years for humans, we found that the mice who ate the diet higher in healthy fats had better cardiac function, less weight gain and better glucose metabolism and insulin resistance than the mice who ate the same amount of calories, but more saturated fat,” Carbone said. “That suggested to us that perhaps it is not just the quantity, but the quality of the diet that we eat that plays an important role in overall health.”

After conducting the second round of preclinical research, Carbone felt ready to launch a feasibility study to ensure that people would comply with a prescribed diet of increased unsaturated fatty acids. “If I was in Italy, I wouldn’t have needed to do a feasibility study because people are already consuming most of the food we recommend in our study, but here we wanted to make sure people knew what the foods were and how to incorporate them into their diet,” he said.

With pilot funding from the Pauley Heart Center and the VCU School of Medicine Department of Internal Medicine, Carbone and his research team enrolled nine VCU Health patients in a 12-week dietary intervention aimed at having participants consume a recommended daily amount of foods rich in unsaturated fatty acids. The results of the study, which published in August in the Journal of the American College of Cardiology Basic to Translational Science academic journal, demonstrated for the first time in scientific history that a dietary intervention aimed at increasing unsaturated fatty acid consumption was feasible and had the potential to improve cardiorespiratory fitness in people with severe obesity and HFpEF.

“Larger randomized controlled trials to test the efficacy of unsaturated fatty acid supplementation on cardiorespiratory fitness and clinical outcomes, as well as understanding the mechanisms through which unsaturated fatty acids may exert these beneficial effects are clearly warranted,” Carbone said in the journal article.

Supporting success

Based on the data obtained through the feasibility study, Carbone was able to secure a three-year, $231,000 grant from the American Heart Association in April to continue his research. The Clinical Research Voucher through the Wright Center supplements the research he is conducting through the AHA-funded study.

Carbone, now an assistant professor in the VCU College of Humanities and Sciences Department of Kinesiology and Health Sciences, hopes the data he gathers from his work at the Clinical Research Unit will inform a larger, multicenter clinical trial that will examine the effects of a diet rich in healthy fats on clinical outcomes, such as reduced mortality and reduced risk of hospitalization for HFpEF.

“Hopefully, if this study goes well, we will be able to do a larger study where we don’t just look at exercise capacity and biomarkers, but also clinical outcomes such as hospitalization and mortality,” he said, adding that he plans to apply for funding from the National Heart, Lung, and Blood Institute at the conclusion of the current clinical research study. “A dietary intervention aimed at improving the quality of the diet, independent of changes in daily caloric intake, has the potential to change the way we treat patients with obesity and HFpEF.”

Wright Center funds pilot study aimed to help patients experiencing post-intensive care syndrome

A ceiling mounted hospital directional sign highlighting the way towards the intensive care unit - 3D render

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

As a nurse at Virginia Commonwealth University Medical Center’s Medical Respiratory Intensive Care Unit, VCU School of Nursing clinical assistant professor Tracye Proffitt met with a former ICU patient when he returned to the hospital a year after leaving to present to the nursing staff. “He talked about his memories of experiencing delirium in the ICU,” she said of the former patient who spent four weeks at the 27-bed unit that specializes in the care of critically ill adult patients with a range of respiratory and medical conditions.

The former patient spoke about experiencing new psychological symptoms after leaving the hospital, including feelings of depression, anxiety and post-traumatic stress. “He didn’t name the symptoms, but he talked about how he had always been laid back, and after he went home he was trying to micromanage everything and had delusional memories,” she said.

Proffitt recognized the patient’s experience as a condition clinically referred to as post-intensive care syndrome. “People who survive an illness requiring a stay at the intensive care unit sometimes experience health problems including cognitive impairment, physical weakness, and psychological symptoms such as depression, anxiety and post-traumatic stress,” she said. “Having one or more of those problems as a new or worsening symptom after being discharged from the ICU is what we call post-intensive care syndrome.”

Inspired to help people like the patient who she met with that day, Proffitt decided to study how post-intensive care syndrome symptoms are related. In August, she received funding from the VCU C. Kenneth and Dianne Wright Center for Clinical and Translational Research to support her research.

“Post-intensive care syndrome has been well-studied in the literature, but what is less studied is if and how the health problems are related to one another,” Proffitt said. “I think having related problems could make one problem or the other worse. For example, having cognitive impairment could compound depressive symptoms.” She also suspects that having more than one problem likely decreases people’s health-related quality of life.

Proffitt, who is pursuing a doctoral degree at VCU School of Nursing, plans to recruit 50 participants from the VCU Medical Center Medical Respiratory ICU to participate in a pilot study that she is leading investigating associations among post-intensive care syndrome symptoms. With support from the Wright Center Clinical Research Voucher Program, a funding mechanism that provides vouchers to researchers that are equivalent to up to $10,000 in clinical services for research, Proffitt will conduct her work at the VCU Medical Center Clinical Research Unit.

Headshot of Tracye Proffitt
Trayce Proffitt

“By providing services at locations where patients already receive care in the health system, we hope to increase access to research, which will lead to better treatment for our patients,” said Mary Harmon, Ph.D., VCU Health Director of Clinical Research.

Located on the eighth floor of VCU Medical Center’s North Hospital, the Clinical Research Unit provides VCU Health clinicians and researchers with the physical space and support necessary to conduct clinical research. The unit includes exam rooms, interview spaces, clinical equipment and infusion chairs. It is staffed by experienced interdisciplinary nurses and technicians who are specially trained to carry out clinical research studies within a culture of patient safety, quality and compliance.

Proffitt expects the funding received from the Wright Center to aid her with recruiting participants. “It would be difficult to recruit people into the clinical trial if I had to ask them to meet at a place they were not already familiar with,” she said. “The Clinical Research Unit provides me with a consistent, guaranteed location where I can meet with the participants.”

Proffitt’s study aims to determine the associations among delirium, cognitive status, functional status, and psychological symptoms such as depression, anxiety and post-traumatic stress in adult ICU survivors at hospital discharge and one-month after hospital discharge. The Wright Center Voucher will cover the cost of using the Clinical Research Unit for the second visit, at which she will meet with participants in the unit’s outpatient exam rooms. “After a month, most patients will be back at home,” she said. “I wanted to have a space available to meet them at that would be familiar and easy to get to.”

She describes the current research as a descriptive study to learn about what ICU patients experience after leaving the intensive care unit, but eventually she would like to develop an intervention to try to prevent and treat problems associated with post-intensive care syndrome. She also hopes to disseminate her study findings at research conferences and through publications in peer-reviewed journals.

“I want to help the patients who we take care of in the intensive care unit have the best quality of life possible after leaving the hospital,” she said. “The support I received from the Wright Center will help me get the research off the ground.”

 

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.”

VCU Wright Center sends six students and faculty members to national translational science conference

This week, more than 1,000 researchers from around the country will descend on the nation’s capital to hear from translational research experts, discuss their research findings, develop their careers, and speak with legislators about the value of scientific research at the Translational Science 2019 conference, held March 5 through 8 in Washington. The Wright Center provided a travel allowance toward attending the conference for six early-career faculty members and students who will be presenting their research posters at the four-day conference. Before they left, we caught up with the researchers to discuss their science, what they were most looking forward to about the conference, and how the Wright Center has supported them with education, training and resources to help improve the translational research process.

 

Hayley Billingsley, graduate student in health and movement sciences, Department of Kinesiology and Health Sciences, VCU College of Humanities and Sciences, and research assistant, Division of Cardiology, Department of Internal Medicine, VCU School of Medicine

“Increased Monounsaturated Fat Consumption is Associated with Improved Body Composition in Subjects with Obesity and Heart Failure with Preserved Ejection Fraction”

Description of research: In a 12-week pilot study aimed at supplementing healthy fats (mono- and polyunsaturated fatty acids) in people who had heart failure with preserved ejection fraction, increasing monounsaturated fatty acids in the diet was associated with a decrease in participants’ percent body fat, which is the amount a person’s weight is composed of fat mass. Monounsaturated fatty acids are found in foods such as extra virgin olive oil, nuts and avocados.

Impact of research: Heart failure patients currently lack evidence-based nutrition therapies. We hope this pilot study will lead to further work exploring the role of mono- and polyunsaturated fatty acids as a potential nutrition therapy for these patients.

Wright Center support: I’m grateful for the Wright Center’s financial support, which has allowed me to attend Translational Science 2019.

Translational Science 2019: I’m looking forward to networking with other research professionals and learning about the NIH grant application process in conference sessions that are aimed at helping young investigators further their research.

 

Justin Canada, Ph.D., assistant professor, Division of Cardiology, Department of Internal Medicine, VCU School of Medicine, and clinical exercise physiologist, VCU Health Pauley Heart Center

“Percent Predicted Peak Exercise Oxygen Pulse is a Marker of Cardiac Reserve Following Thoracic Radiotherapy”

Description of research: Individuals who receive radiation therapy as part of treatment for chest cancers may be at risk of future cardiovascular events due to incidental radiation exposure of the heart. This can lead to symptoms of significant fatigue and shortness of breath before the diagnosis of heart problems. Measuring oxygen consumption changes during exercise may prove to be an early marker of anti-cancer treatment-related toxicity.

Impact of research: In the future, the hope is that this line of research will lead to diagnostic procedures that may help better risk-stratify cancer survivors who may be at risk of cardiotoxicity related to anti-cancer therapies such as radiotherapy and/or chemotherapy.

Wright Center support: This research would not have been possible without the support of the Wright Center, which included providing access to resources at the VCU Medical Center Clinical Research Unit. My research relied on services that were provided at the unit, including phlebotomy and nursing personnel, lab space, and echo and stress testing systems. My mentor, Wright Center associate director Antonio Abbate, M.D., Ph.D., who is also the medical director of the Clinical Research Unit, remains invaluable to my continued learning and growth as a clinical researcher.

Translational Science 2019: The conference hosts a National Institutes of Health Mock Study Section, which provides early-career investigators such as myself with the opportunity to review grant proposals alongside actual NIH study section members. I’m looking forward to hearing the thoughts, questions and concerns that arise as the NIH study section members review my prospective grant applications.

 

Salvatore Carbone, Ph.D., research instructor of medicine, Division of Cardiology, Department of Internal Medicine, VCU School of Medicine, and research nutritionist, VCU Health Pauley Heart Center

“A Dietary Intervention to Increase Unsaturated Fatty Acids in Patients with Obesity and Heart Failure with Preserved Ejection Fraction: An Analysis of the UFA-Preserved Pilot Study

Description of research: We found that a diet aimed at supplementing healthy fats — also called unsaturated fatty acids, — which are found in foods like extra-virgin olive oil, mixed nuts, avocado, canola oil, and fatty fish, —  resembling the Mediterranean dietary pattern, — resulted in positive changes in the levels of fatty acids in the blood, which were in turn associated with improved exercise capacity in patients with obesity and a specific form of heart failure, called heart failure preserved ejection fraction (HFpEF).

Impact of research: About half of patients with heart failure present with HFpEF, and up to 80 percent of those with HFpEF are, in turn, overweight or obese. HFpEF lacks beneficial therapeutic strategies, so we believe the results of our study are important, as they lead to the development of a novel therapeutics in this population. We need to repeat our intervention in a larger population to confirm our findings, but the preliminary data is promising.

Wright Center support: The study was conducted in the VCU Medical Center Clinical Research Unit, which provides state-of-the-art equipment and personnel to perform high-quality research. The study was funded by the Department of Internal Medicine and the VCU Pauley Heart Center, which funds pilot projects to junior faculty like myself who are collaborating with senior faculty members.

Translational Science 2019: Being able to present data is always a great opportunity. I have been working on this project for the past three years, and receiving feedback from investigators from other institution will be very important as I move forward. Additionally, attending the conference allows me to networking with junior faculty like myself and also with senior investigators who have similar research interests, thus facilitating potential future collaboration with researchers from other institutions.

 

Dinesh Kadariya, M.D., assistant professor, Division of Hospital Medicine, Department of Internal Medicine, VCU School of Medicine, and cardiovascular research fellow, VCU Health Pauley Heart Center

“Incidence of Takotsubo Cardiomyopathy in a Large, Urban Hospital in USA”

Description of research: Takotsubo cardiomyopathy, also known as broken heart syndrome, is an acute heart condition in which patients present to a hospital with chest pain. Due to increased awareness, the incidences of this condition being recognized are rising, but the true incidence rate and risk factors are not well known. We evaluated the incidences of takotsubo cardiomyopathy compared to another acute heart condition that can have similar presentation, called non-ST elevated myocardial infarction, in the past eight years at VCU Medical Center.

Impact of research: Although takotsubo cardiomyopathy is typically considered benign, serious complication can happen in some cases. Increased awareness would help clinicians make the diagnosis early. Additionally, having a clearer understanding of risk factors associated with the condition may help to reduce incidences. The study was done for the first time in Richmond, and it will add to the knowledge-base and awareness of the condition among health care providers around the world.

Wright Center support: The Wright Center informatics team provided me with access to the data through TriNetX, which is a system that provides access to patient records in a de-identified, HIPAA-compliant manner. Additionally, Wright Center director F. Gerard Moeller, M.D., and associate director Antonio Abbate, M.D., Ph.D., supervised the design, analysis and presentation of the study.

Translational Science 2019: I’m looking forward to meeting the other conference attendees who are motivated and enthusiastic to discover new things that will advance the medical sciences and help future generations live healthier lives.

 

Amy Northrop, Ph.D. candidate, Department of Human and Molecular Genetics, VCU School of Medicine

“Targeting DDI2 to Potentiate Proteasome Inhibitor-induced Cell Death in Triple-Negative Breast Cancer Cells”

Description of Research: The proteasome is widely regarded as a recycling center in the cell — responsible for degrading proteins that are mutated, misfolded, or not needed by the cell at that time. Cancer cells are highly dependent on the proteasome to degrade the copious amounts of mutant proteins they produce, and allow them to rapidly divide, but proteasome inhibition as a cancer therapy has largely failed to effectively treat most types of cancer. One explanation for this failure is a compensatory cellular mechanism called the NRF1-mediated proteasome bounce-back response, which allows the cell to respond to proteasome inhibition and evade cell death by making more, uninhibited proteasomes to prevent the build-up of proteins that need to be degraded. My research focuses on therapeutically crippling the bounce-back response to allow proteasome inhibitors to more effectively kill many types of cancer cells, thus (hopefully) expanding the repertoire of cancer types for which proteasome inhibition can be used as an effective cancer therapy.

Impact of research: The research is currently focused on triple-negative breast cancer (TNBC), but if we are able potentiate proteasome inhibitor-induced cancer cell killing using TNBC as a model, there may be broader implications for other types of cancer that have also been previously unresponsive to proteasome inhibition as a therapeutic.

Wright Center support: The Wright Center is providing me with a travel allowance to attend the conference. I would neither have submitted an abstract, nor be attending, if it were not for the Wright Center.

Translational Science 2019: I’m most looking forward to participating in the Capitol Hill advocacy visit on Wednesday, where I will join other researchers in meetings with state senators and representatives to talk about the importance of funding clinical and translational science.

 

Cory Trankle, M.D., chief cardiology fellow, Cardiovascular Disease Fellowship, Department of Internal Medicine, VCU School of Medicine

“Interleukin-1 Blockade in Patients with Pulmonary Arterial Hypertension and Right Ventricular Failure” and “Alirocumab in Acute Myocardial Infarction: Results from the Virginia Commonwealth University Alirocumab Response Trial (VCU-AlirocRT)”

Description of research:

“Interleukin-1 Blockade in Patients with Pulmonary Arterial Hypertension and Right Ventricular Failure”: Pulmonary hypertension is a rare, but dangerous disease involving high pressures in the arteries leading to the lungs. Studies involving animal models of pulmonary hypertension suggested that targeted anti-inflammatory therapy could be beneficial in this disease state. We tested, for the first time in this population, an open-label treatment of anakinra in patients with pulmonary arterial hypertension, showing that we could safely reduce the inflammation levels. There were some encouraging additional findings, including that patients felt better overall on the therapy, and the reductions in inflammation were correlated with improvements in their ability to exercise.

“VCU-AlirocRT”: There are two new powerful cholesterol-lowering medications called PCSK9 inhibitors, which are Food and Drug Administration-approved. One of them — alirocumab — has shown that patients with a history of heart attacks (one to 12 months before starting treatment) overall have fewer events (heart attacks, stroke, or death) if they receive this medication. However, there has never been a study evaluating the use of alirocumab at the timeof a heart attack. We tested, for the first time in a randomized, placebo-controlled, double-blind study, the use of alirocumab in patients being admitted to the hospital with a heart attack. We showed that it is safe and effective in lowering the “bad” cholesterol — LDL cholesterol — within 72 hours of a heart attack. Determining if this will result in improved outcomes will require larger studies.

Impact of research: The research could potentially help patients with pulmonary arterial hypertension, which is a rare disease that is in dire need of better treatments, and patients who are coming to the hospital with heart attacks.

Wright Center support: The Wright Center provided the facilities for the pulmonary arterial hypertension study, particularly the VCU Medical Center Clinical Research Unit, which allowed for a one-stop location to provide a wide array of sophisticated testing: cardiopulmonary exercise testing, echocardiography, and phlebotomy with biomarker measurement. The alirocumab study was also supported by the Clinical Research Unit, which allowed for phlebotomy and biomarker measurements and clinical visit coordination.

Translational Science 2019: I’m looking forward to having the opportunity to broadcast our research findings and discuss our research with experts in the field.

Can liver disease be linked to heart failure? VCU study highlights liver-heart interaction

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

Virginia Commonwealth University researchers have collaborated on a clinical trial that identifies indicators for nonalcoholic fatty liver disease — a typically asymptomatic disease caused by fat buildup in the liver and the leading cause of liver disease in the United States.

Mohammad Siddiqui, M.D., an associate professor in the VCU School of Medicine, and researchers with expertise in cardiology, hepatology, and exercise physiology have been conducting research with a focus on the link between heart and liver damage. Their efforts have resulted in a study in which they draw a connection between patients with aggressive types of fatty liver disease and limitations in exercise capacity.

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Interdisciplinary VCU research team provides clinical and diagnostic guidance for broken-heart syndrome

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

 

Infographic describing broken heart syndrome
Broken heart syndrome usually results from severe emotional or physical stress such as the death of a loved one. (Image courtesy of the Journal of the American College of Cardiology)

A team of cardiology and psychiatry specialists from Virginia Commonwealth University has authored a new comprehensive clinical review article in the Journal of the American College of Cardiology that summarizes the latest evidence-based diagnostic criteria and treatment strategies for Takotsubo cardiomyopathy, also known as broken-heart syndrome.

“Takotsubo cardiomyopathy is a recently recognized condition that is difficult to diagnose and treat,” said corresponding author Antonio Abbate, M.D., Ph.D. Abbate is a cardiology professor at VCU School of Medicine. He serves as associate director of the C. Kenneth and Dianne Wright Center for Clinical and Translational Research and as medical director of the Clinical Research Services unit. Read More

Heart Symposium

The Wright Center for Clinical and Translational Research hosts nationally and internationally known speakers for heart symposium!

Heart failure is a complex clinical syndrome in which the heart function is impaired to the point that the patient becomes limited by shortness of breath and fatigue.

On May 20, cardiologist experts in advanced heart failure management and specialists in pulmonary hypertension came together at VCU for a heart symposium.
The event, organized by the Wright Center for Clinical and Translational Research, focused on the management of the patients that have heart failure complicated by an elevation in the pressure in lung circulation and/or failure of the right ventricle.  The seminar was held in occasion of the American Thoracic Society conference in Washington, D.C.
The symposium, hosted by Wright’s CCTR, Dr. Antonio Abbate, MD, PhD, ‘Roberts’ Professor of Cardiology and Medical Director of the Clinical Research Unit, included an exclusive list of nationally and internationally known speakers.  The seminar brought together faculty from VCU’s Cardiology and Pulmonary Divisions as well as colleagues from Levinson Heart Failure Clinic, HCA, and Bon Secours’ Heart and Vascular Institute. 
Dr. Norbert Voelkel, MD, former and founding director of the Victoria Johnson Research Center for Pulmonary Disease at VCU, and Dr. Richard Cooke, Associate Professor of Medicine and former Chief of the Heart Failure section at VCU, served as moderators to the session. Andrew Keller, MD, Medical Director of the Levinson Heart Failure Clinic at Chippenham Hospital, HCA, opened the session by discussing a complex case of refractory cardiogenic shock secondary to severe right ventricular failure in a patients supported by a left ventricular assist device.
Roberta Bogaev, MD, Director of the Heart Failure Program at Bon Secours Heart and Vascular Institute, gave an overview of the clinical significance of pulmonary hypertension and right ventricular dysfunction in heart failure. Harm Bogaard, MD,  a prior faculty member and Professor from the VU University, Amsterdam, Netherlands, presented on the complex pathophysiology of pulmonary hypertension in heart failure.
Dr. Melissa Smallfield, MD, Heart Failure program at VCU, presented on the management of the patient developing right ventricular dysfunction and pulmonary hypertension after left ventricular assist device. Daniel Grinnan, MD, Associate Professor of Medicine and Director of the Pulmonary Hypertension program at VCU, reviewed the current treatment strategies for pulmonary arterial hypertension.
The session concluded with Dr. Voelkel, a scientist with an extensive publication and funding record in his more than 40 years of research, telling the audience about the challenges of, and concomitant need for, paradigm defying research.