The fund supports pilot work that uses the Wright Center’s research-dedicated MRI. The submission deadline for applications is Feb. 21.
The goal of this study is to show that MRI is a safe and accurate method to assess the cardiovascular function of children with pulmonary hypertension. Success in this study has the potential of shifting the paradigm of pediatric pulmonary arterial hypertension care towards a safer, non-invasive monitoring modality and significantly improving quality of life in children with pulmonary hypertension.
Across the world, many years ago, doctors would prescribe unappealing concoctions of human and animal stool a treat a number of stomach ailments. And, in the last 10 years, clinical trials have begun to confirm why.
“There’s really a factory inside our bellies,” says Jasmohan Bajaj, M.D., a gastroenterologist and liver specialist at Virginia Commonwealth University. “Anything that we eat or drink, any medicines we take, when we get sick – the microbes are affected one way or the other. Either they are related to it, they process it, or they make us either resistant or prone to it.”
Bajaj is a major contributor to growing evidence that the unique collection of bacteria in our guts informs our health – sometimes in surprising ways. Fecal microbiota transplants – the newer, less unappealing version of that ancient treatment – are a big part of his research. And he’s leveraging the resources of the C. Kenneth and Dianne Wright Center for Clinical and Translational Research to accomplish his trials and study to become a leader in the field.
Working at a university with a Clinical and Translational Science Award (CTSA) from the National Institutes of Health, Bajaj has been awarded multiple grants that support his research into gut biomes and the uses of fecal transplants.
An R21 grant for 2017-18 helped Bajaj perform a randomized trial of fecal microbial transplant in patients with cirrhosis and hepatic encephalopathy.
This year he received another R21 grant to continue research into liver transplant outcomes, collaborating with a researcher another CTSA hub, the Columbia University Irving Institute for Clinical and Translational Research. The study will assess gut microbiota in patients with liver transplants in relation to their outcomes.
And he recently submitted an R01 to develop gut microbiota as a treatment for alcohol use disorder.
Bajaj also uses facilities maintained and funded by the Wright Center for his research. The Collaborative Advanced Research Imaging facility gives him access to a research-dedicated MRI scanner, which he’s using to analyze brain function in patients with cirrhosis before and after treating them with a gut-specific antibiotic.
A prolific summer of translational results
This summer, Bajaj published four articles showing the link between gut bacteria, cirrhosis and health. Read More
The Wright Center is joining forces with the Pauley Heart Center this year to offer an up-to-$50,000 grant to VCU faculty.
This one-time funding opportunity for a pilot project is intended to stimulate new collaborative initiatives and support critical experiments that will lay the groundwork for further funding and published research. Pauley and Wright seek studies that research vascular disorders, dysfunction or disease pertaining to the nervous or circulatory systems.
Matthew Barrett, M.D., M.Sc., an associate professor of neurology, received funding for a project titled “Multimodal MRI biomarker of cholinergic basal forebrain degeneration in Parkinson disease dementia.”
Nancy Jallo, Ph.D., RNC, and Lisa Brown, Ph.D., R.N., associate professors of nursing, received funding for a project titled “Effect of cannabis on brain connectivity associated with maternal attachment: A pilot study in postpartum women.”
Wally Smith, M.D., a professor of internal medicine, received funding for a project titled “Neuroimaging of hemodynamic functions in sickle cell disease.”
Uyen Truong, M.D., an associate professor of cardiology, received funding for a project titled “The impact of bariatric surgery on adolescent cardiovascular function.”
The pilot grants allow these clinicians to accrue crucial early data – that they can then evaluate for full-scale feasibility. The grants are for amounts up to $25,000.
The National Institutes of Health’s (NIH) Clinical and Translational Science Award funds the grants, which the Wright Center administers (UL1TR002649). The NIH funds more than 50 medical research institutions across the United States in their work to speed the translation of research discovery into improved patient care. And at the Wright Center, that means wraparound support services – from protocol building to funding to mentorship – for VCU researchers.
Imagine this: You’re walking down the street in the middle of the day when you encounter a stranger crouched and crying on the sidewalk. Is your instinct to comfort the person or to use their emotional vulnerability to hurt them?
“Most people can sense when others are in pain,” said David Chester, Ph.D., an assistant professor of psychology at Virginia Commonwealth University. “Whereas non-psychopathic people use that information to console the person, a psychopath might use it to hurt them.”
This conduct — something Chester refers to as “antisocial empathy” — is a trademark behavior of psychopaths. “Psychopaths use antisocial empathy all the time in the real world,” he said. “They possess the ability to feel empathy. They just use it to hurt, whereas everyone else uses it to help.”
“For this study, I’m shifting my focus from studying the act of violence to look at what is going on in the brains of psychopaths before they cause harm,” Chester said. “The idea is that once they’re in the act of hurting someone, you’re already too late. If we want to prevent violence, we need to understand what happens beforehand.”
For centuries, psychologists and neuroscientists maintained the conventional wisdom that psychopaths could not feel empathy. “For a really long time, the prevailing viewpoint was that psychopaths were born without empathic ability,” Chester said.
It wasn’t until advancements in brain imaging technology enabled researchers to investigate the physiological mechanisms that underlie human behavior that scientists began to question that commonly held belief.
“When we started getting better at brain imaging and being more subtle with our experimentation, we realized that psychopathic individuals can be empathetic,” Chester said, noting recent studies in which psychopaths were motivated to feel empathy for others.
In the studies, psychopathic individuals, while in MRI scanners, were shown videos of people experiencing pain. Without incentive, the signature biomarkers of empathy that can be read on a brain scan remained dim in the psychopaths’ brains, but when motivated to empathize, the psychopaths’ brains displayed the same levels of empathy as normal individuals.
“So it’s not that they can’t empathize, it’s just that they don’t,” Chester said. “It’s more a lack of motivation than a lack of ability.”
Building from the foundation that psychopaths can choose to feel empathy, Chester’s research team will be the first to investigate the inner workings of the brain when psychopaths are motivated to feel antisocial empathy. “We are trying to understand what is going on in the brain to cause psychopaths to choose not to use that function,” he said. He hopes the research will fill a gap in the scientific understanding of psychopathic behavior.
“If you give psychopaths a reason to feel empathy that fulfills their selfish goals — because that is all they really care about — then they can turn empathy on,” Chester said. “Just giving psychopaths something like money will incentivize them, but really what psychopaths want is to harm other people. That is what they are really motivated to do.”
Chester designed the Pilot Imaging Fund research study to do just that — motivating participants to empathize with others, with a reward of causing harm if they did.
For the pilot study that was conducted at the Wright Center’s Collaborative Advanced Research Imaging facility, the researchers recruited 46 adult male participants. Half of the men were at the low extreme of the psychopathy continuum and half at the high extreme, as determined by results from a questionnaire that identifies degrees of psychopathic traits.
While undergoing neuroimaging in the MRI, the research participants were shown scientifically validated images of faces of individuals who are simulating being hurt in various ways and to varying degrees — through shocking, burning and poking. The images were from a database of painful expressions collected by Peter Mende-Siedlecki, Ph.D., an assistant professor of psychological and brain sciences at the University of Delaware.
“He took pictures of people pretending to experience pain,” Chester said. “Sometimes it looks like it’s just a little bit of discomfort, all the way to excruciating pain.”
The VCU research participants thought they were participating in a study on how the brain makes decisions. They were told the images were of separate groups — VCU and University of Richmond students — to manufacture an “us versus them” mentality, and they were instructed to assess the degree of pain that they thought the people in the photos were experiencing. For example, by analyzing their facial expression, is it possible to discern if the University of Richmond student feels more pain from shock or from burning? At the end of the study, the participants were told to apply the most painful stimuli to the University of Richmond students and the least painful to the VCU students.
“The study participants are motivated to be accurate because they want to find the thing that hurts the University of Richmond students the most and the VCU students the least,” Chester said. “They are trying to be empathic in both conditions, but the difference is that in one condition, they are trying to be empathic so they can hurt others, and in the other condition they are trying to be empathic so they can help — antisocial versus prosocial empathy.”
An antidote to antisocial empathy
The researchers predict that psychopathic individuals will access the brain’s cognitive empathy network when doing so facilitates antisocial goals, such as harming a competitor, and that this neural recruitment will predict greater aggression toward their targets.
“If supported, this novel approach would readily translate into new motivation-focused interventions and would inform biological and psychological models of the monumentally costly phenomenon of psychopathic aggression,” said study co-principal investigator Nicholas Thomson, Ph.D., a forensic psychologist with VCU Health’s Injury and Violence Prevention Program and an assistant professor in the VCU School of Medicine Department of Surgery.
Chester and Thomson expect the findings to forge a potential new frontier for research on psychopathy, empathy and aggression.
“The great thing about pilot studies is that they fund projects that are groundbreaking,” Chester said. “We have predictions of how we think it is going to go, but it is so new and innovative that we really don’t know what is going to happen. The point of the pilot study is that by the time we’re done with this, we will have an initial idea of what the effects are and how strong they are.”
The researchers plan to apply for federal funding from the National Institutes of Health to launch a larger study after the pilot study concludes next year. “The idea is that we are going to take our findings and turn them right into a much larger grant application,” Chester said, adding that they hope to recruit men and women from diverse backgrounds to capture the nuanced, continuous nature of psychopathy.
Ultimately, the team hopes to discover an antisocial empathy circuit in the brain, which could be targeted with pharmacological therapies aimed at reversing antisocial empathy behavior. “We can identify people who are at risk for violence, but these risk assessments rarely include biomarkers,” Thomson said. He hopes the study reveals better targets for preventing violence among psychopathic individuals.
“The idea is that this research, hopefully in the future, will lead to the development of biologically informed treatment strategies that might be able to change activation in empathy circuits in the brain.”
“I sometimes feel helpless because I can’t do much for them at that moment other than saying some kind words,” Zhu said. “Those are the moments that help me focus on my research to potentially have an impact that can change or improve therapeutic outcomes for cancer patients.”
Leveraging an extensive background in engineering, chemistry, and pharmacology, Zhu leads a research team of six postdocs and graduate students, as well as multiple undergraduate students and visiting scholars. His team designs targeted drug delivery systems and develop cancer nanomedicines such as nucleic acid nanovaccines for enhanced therapeutic benefit. Nanovaccines dispense microscopic particles into the immune system to stimulate a response against cancer cells. They hold promise for treating disease more effectively than existing vaccines. Zhu tests a variety of nucleic acids, including immunomodulatory DNA/RNA, gene-expression modulation DNA/RNA, drug-encoding mRNA or gene-editing nucleic acids.
Zhu currently holds several grants to support studies on nanovaccines for glioma, a tumor of the brain and spinal cord, and melanoma, the deadliest form of skin cancer.
Under the mentorship of VCU School of Medicine professor Steven Grossman, M.D., Ph.D., Zhu holds an American Cancer Society Institutional Research Grant to study the combination of immunotherapy and immuno-activating chemotherapy to treat melanoma. He is also a principal investigator on a VCU Massey Cancer Center pilot project that will explore the combination of a nanovaccine, immune re-energizing drugs and radiation therapy to treat glioma in mouse models.
“This project is really exciting because there isn’t a durably effective treatment option for glioma,” Zhu said. “We hope that by using radiation we can jump-start the tumor microenvironment to make immunotherapy more effective.”
Zhu grew up in China, where he earned a bachelor’s degree in biotechnology from Nankai University. He later moved to the U.S., where he earned a doctorate in medical science and completed a postdoctoral fellowship in cancer nanomedicine at the University of Florida. He finished a second postdoctoral fellowship in cancer immunotherapy and bioimaging at the National Institute of Biomedical Imaging and Bioengineering in Maryland. During this time, Zhu collaborated in well-established laboratories to engineer and image nanomedicines. It was after this fellowship that he focused his research on cancer immunotherapies.
“The scientific combination of pharmaceutics and cancer research offers an ideal environment for me to continue my career at Massey,” he said.
Zhu has published more than 70 articles in peer-reviewed journals, including Nature Communications and Proceedings of the National Academy of Sciences. His publications have been cited by peers more than 4,500 times in the past five years. He is a member of the American Chemical Society, the Oligonucleotide Therapeutics Society and the Society for Immunotherapy of Cancer. He received a Distinguished Scientist Award from the National Institutes of Health in 2017 and was awarded the Alan M. Gewirtz Memorial Fellowship by the Oligonucleotide Therapeutics Society in 2013.
He lives with his daughter and mother in Richmond, and the family awaits the arrival of his wife, who is close to finishing her doctoral degree in food science and nutrition in Maryland.
Re-purposed from an article by Blake Belden, VCU Massey Cancer Center
While completing a doctorate in clinical psychology at Virginia Commonwealth University, Amma Agyemang, Ph.D., developed an interest in the effects that chronic medical conditions have on sleep and cognitive functioning. For her dissertation, she tested an online therapy for insomnia among people who were newly diagnosed with cancer.
“One of the key weaknesses of the study was that we didn’t have objective data,” she said of the intervention that measured sleep quality subjectively through diaries and a self-reported questionnaire. “I always wanted to do a study that measures sleep objectively.”
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. VCU received the $21.5 million award in May 2018.
“An expanded and diverse workforce is essential to inspire relevance and innovation in clinical and translational science,” said Wright Center Director F. Gerard Moeller, M.D., adding that the Wright Center is committed to enhancing the diversity of the translational workforce through mentoring, training and funding opportunities.
Agyemang’s research is aimed at characterizing sleep disruptions and measuring the relationship between sleep and cognitive functioning in individuals with mild traumatic brain injuries. She is also interested in developing interventions and clinical tools to address sleep and cognitive difficulties.
“I’m hoping we can find that sleep is a huge contributor to overall cognitive functioning and that, if we can change it, then people’s thinking and memory will improve,” she said.
To conduct her research, Agyemang will leverage the ongoing CENC study, which has gathered more than 1,500 individuals who undergo a comprehensive evaluation including diagnostic interviews, symptom and quality-of-life questionnaires, neurocognitive testing and neuroimaging. The supplement will enable Agyemang to recruit participants from the Richmond cohort to participate in her research. Participants will wear a motion biosensor watch for one month, and the watch will collect data by monitoring their rest and activity cycles — a noninvasive method of monitoring known as actigraphy.
“With the support from the Diversity in Health-Related Research supplement, I’ll be able to just focus on getting participants’ objective sleep data through actigraphy, and we’ll have the cognitive data because that already has to be collected as part of CENC, so it is a very low participant burden study,” Agyemang said.
In the course of two years Agyemang hopes to recruit approximately 100 research participants. The biosensor will objectively measure physiological aspects of sleep quality. Combined with the information collected through the CENC study, the data produced from the motion biosensor watch will allow Agyemang to objectively assess if people who have poor sleep also have poor cognitive functioning.
“It is a great opportunity for me as a junior faculty member to get funding for my career development,” Agyemang said, adding that she is interested in applying for NIH funding and expects that the work she does through the supplement will provide the groundwork she needs to secure that funding in the future.
“The work I do through the Diversity in Health-Related Research supplement will help me build my area of expertise and accumulate data to support larger federally funded research projects,” she said.
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.”
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.
“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.
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.”
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.
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 firstname.lastname@example.org or 804-828-0067.