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SPRING 2014

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VOLUME 13, NUMBER 1

Trio of MD-PhD students earn first author credits

With 58 students currently enrolled, the medical school’s M.D.-Ph.D. program has tripled in size in the last decade. Most students complete the program in about seven years, roughly divided between clinical and science training. This combined training is geared toward equipping physician-scientists who will transform scientific breakthroughs into effective treatments for patients. These three current students have seen early success, earning first author credit on recent publications.

This winter, TIM KEGELMAN (center) was first author of a study published in the journal Neuro-Oncology. He and his colleagues identified the gene that is a driving force behind the aggressiveness and invasive nature of glioblastoma multiforme, the deadliest form of brain cancer. Tim is currently completing the graduate study portion of the M.D.-Ph.D. program in the lab of his thesis adviser Paul B. Fisher, Ph.D., chair of the Department of Human and Molecular Genetics. The lab uses discoveries in cancer molecular genetics to develop new treatments that halt or reverse tumor progression. This is Tim’s eighth publication, but first as lead author.

For his dissertation, RAHUL MAHAJAN studied how ion channels control electrical activity in the heart and brain. His findings show how these channels function on the atomic scale and could lead to the development of treatments for life-threatening irregular heartbeats. They have already led to his being first author on a study published on the cover of Science Signaling, a publication of the American Association for the Advancement of Science. Studying under the mentorship of Diomedes E. Logothetis, Ph.D., the chair of the Department of Physiology and Biophysics, Rahul is finishing medical training in his last year of the M.D.-Ph.D. program. He’ll head to a combined program at Boston’s Brigham and Women’s and Massachusetts General Hospitals for residency training in Neurology, where he plans to continue pursuing research using the methods of structural biology and electrophysiology he learned during his graduate training.

With an interest in the addictive liability of both illicit and pharmaceutical drugs, JULIE BONANO is in the second year of the graduate study portion of the M.D.-Ph.D. program. She studies with thesis advisor Steve Negus, Ph.D., a professor in the Department of Pharmacology and Toxicology. The journal Psychopharmacology recently published Julie’s study on the behavioral effects of various constituents of the headline-grabbing designer drugs known as bath salts. In animal studies, she discovered that these compounds altered behavior in ways similar to other known drugs of abuse. Her findings suggest that bath salts may be as likely to cause abuse and dependence as other well-known stimulants like methamphetamine or ecstasy.

INSIDE THIS ISSUE

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Partners for Discovery

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New Recruits

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Tiny Table Saws

4

Alumni Star

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Helping Kids in Bangladesh

School of Medicine

6

Honors & Accolades

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Research Notes

In the tradition of the Medical College of Virginia


[ PARTNERS for DISCOVERY ] Lance J. Hampton, M.D. >>

Barbara and William B. Thalhimer Professor in Urology

As Chair of the Urology Division, Hampton notes that the Thalhimer Professorship Endowment supports his efforts to advance the program in multiple ways, including representing the Division at meetings around the world. Hampton presents and demonstrates advanced surgical techniques that have been developed in our operating rooms. For three of the past five years, he’s also taken a team to Huê´ University in Vietnam, bringing advanced surgical techniques to a region of the world that is severely lacking in modern technology and training. In Huê´, Hampton’s team typically does four or five major open kidney stone cases each day. “With the expansion of minimally invasive surgery for kidney stones, these procedures are extremely rare in the U.S., but are standard practice in Vietnam,” Hampton explains. “This gives my residents and me the opportunity to perform operations that we rarely see anymore.” He says his residents have also benefited from the cultural exchange in other ways. “It has helped each of them to foster a philanthropic spirit, dedicating themselves to ultimately what draws all of us to medicine — the desire to help others.” Read more online >> http://go.vcu.edu/HamptonExchange

Diomedes E. Logothetis, Ph.D. >>

John D. Bower, M.D., Endowed Chair in Physiology

The opportunity to rebuild a department with a distinguished past was a key factor in Logothetis’ decision to join the MCV Campus in 2008 as professor and chair of the Department of Physiology and Biophysics. He arrived with the goal of elevating the department into the top 10 physiology departments in the country. He’s worked for the past five years with an eye on that goal, recruiting nine new faculty members with active research programs. “The publication record of the department has well more than doubled and we have published papers in the most competitive top-tier journals,” Logothetis said. “Despite the challenging funding times, 63 percent of the faculty members are currently funded by the NIH.” In fact, over the last five years, the department’s NIH funding has moved ahead of some 30 departments of its type in the nation, and the department is now ranked among the top 40 in the nation. “It is my great privilege and honor to carry Dr. Bower’s name via the Chair he endowed,” Logothetis said. “With his generosity, he has become an intrinsic part of our department’s success.”

Curtis N. Sessler M.D. >>

Orhan Muren Distinguished Professor

Leading the practice of critical care medicine at the VCU Medical Center is Curtis N. Sessler M.D. Named for one of the nation’s first intensivists, the Endowed Chair carries special meaning for Sessler who knew Muren personally, first when Sessler was a critical care fellow and later when he was a junior faculty member. According to Sessler, Muren’s love of teaching was beyond compare. “In short, he was a living legend.” Sessler’s own enthusiasm for medical educaiton spans all levels, from the patient’s bedside and lecture hall, to mentoring and sharing his experiences with his peer physicians at national and international meetings. Sessler’s influence on the field has grown as he’s regularly called on to develop national guidelines and position statements. In addition, in the past year he authored five book chapters – using these, too, as a means of mentorship by inviting junior colleagues to work alongside him. Later this year, Sessler will assume the presidency of the American College of Chest Physicians. He points out that the College’s missions of education, research and volunteerism reflect his own priorities. You’re as likely to find him teaching NY City school children about the dangers of smoking or visiting a Phoenix market to test the pulmonary function of shoppers as you are to see him speaking to colleagues from a podium.

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Endowed Professorships and Chairs lend support to faculty, new discoveries Endowed professorships and chairs are crucial to the task of attracting and retaining an exceptional faculty. They are powerful fuel for the overall mission of the academic medical center. Such support has the ability to attract renowned teachers and clinicians and augment the research of a top scientist. • Nearly 140 endowed professorships and chairs have been created to benefit the medical school and its faculty. Later this year, VCU will hold an investiture ceremony to bring together the generous donors who have established the endowments along with the faculty members whose work is supported by the funds.

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The VCU Board of Visitors has recently approved the appointments of nine faculty members to Endowed Professorships in the medical school.

Antonio Abbate, M.D., Ph.D. Associate Professor of Internal Medicine APPOINTED TO >>

the James C. Roberts, Esq. Professorship in Cardiology

The James C. Roberts, Esq. Professorship in Cardiology was established in 2001 through gifts from his family, friends and colleagues in recognition of his outstanding leadership of the Campaign for the Heart Center. A former senior partner in Troutman Sanders Mays Valentine, Roberts also guided the Theresa Thomas Foundation Board of Trustees for many years.

Christopher P. Kogut, M.D. Assistant Professor of Psychiatry APPOINTED TO >>

the William and Ruth McDonough Professorship in Graduate Psychiatric Education

A bequest from Ruth McDonough established the McDonough Professorship to support mental health education in Department of Psychiatry. Both Dr. and Mrs. McDonough had ties to the psychiatric field. Mrs. McDonough served as the executive secretary for the Psychiatric Society of Virginia from 1981 to 1996. Dr. McDonough, an alumnus of the medical school’s Class of 1958, completed his residency training in Psychiatry on the MCV Campus in 1962 and went on to become chairman of the department.

Michael C. Kontos, M.D. Associate Professor of Internal Medicine APPOINTED TO >>

the Cardiovascular Professorship

Richard Cooke, M.D.

Associate Professor of Internal Medicine APPOINTED TO >>

the Moses D. Nunnally Professorship Cardiology

The Nunnally Professorship in Cardiology was established in 2000 in memory of Moses D. Nunnally, a community leader and philanthropist, to attract and retain the best and brightest faculty members – physicians, scientists and educators – to the Pauley Heart Center in order to find the causes of and cures for heart disease.

A Navy seaman during World War II, local real estate developer Henry L. Stern was known for his wide and varied interests that included founding the National Steeplechase Foundation in 1995 and supporting the cardiology division over many decades. A gift made through the Stern Foundation established the Cardiovascular Professorship in 1987 with the goal of supporting an eminent scholar of national reputation in the cardiovascular field.

Mark G. Malkin, M.D. Professor of Neurology APPOINTED TO >>

the William G. Reynolds Jr. Chair in Neuro-Oncology

Judith P. Grossberg, M.D. Associate Clinical Professor of Pediatrics APPOINTED TO >>

the Walter E. Bundy, Jr. Professorship in Community Pediatrics

A 1945 MCV alumnus, Walter Bundy played a major role in the Department of Pediatrics’ teaching programs from 1952-1992. Throughout his career, he served as a role model for students, epitomizing the community pediatric practitioner. The Professorship was established to honor his accomplishments and encourage interaction between community physicians and the Department of Pediatrics in regard to providing excellent care and participating actively in the education of future pediatricians.

Gautham Kalahasty, M.D. Associate Professor of Internal Medicine APPOINTED TO >>

the David Richardson, M.D. Professorship in Cardiology

David Richardson’s career on the MCV Campus spanned nearly four decades and included a 14-year tenure as Chairman of the Division of Cardiology. After he stepped down from his full-time responsibilities in the 1990s, the family of local businessman George Whitfield asked that a fund Whitfield had established to improve the quality of education, instruction and study on cardiovascular disease be named to honor Richardson.

Vice President of Government Relations and Public Affairs of the Reynolds Company, William G. Reynolds also lent his leadership to VCU, first as a member of its Board of Visitors and later as a trustee of the MCV Foundation Board until his death in 2003. The endowed chair was created in 2006 by the Richard S. Reynolds Foundation to honor the noted businessman and philanthropist.

Mary Ann Peberdy, M.D. Professor of Internal Medicine APPOINTED TO >>

the C. Kenneth Wright Professorship in Cardiology

In 2011, Ken and Dianne Wright established the professorship that bears his name with the goal of supporting a distinguished faculty member with a strong record of commitment and excellence in advancing the practice of cardiology. For 15 years, the Wrights have generously supported multiple initiatives at VCU including pulmonary disease, the Massey Cancer Center and the School of Engineering.

Dr. Judith Voynow, M.D. Professor of Pediatrics APPOINTED TO >>

the Edwin L. Kendig, Jr., M.D. Endowed Chair in Pediatric Pulmonary Medicine

A pioneer in pediatric pulmonary disease, Edwin Kendig arrived at MCV in 1944. An internationally recognized expert in childhood tuberculosis and sarcoidosis, he is noted for starting MCV’s child chest clinic. In 1991, the endowment that bears his name was established.

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New

U. ADAMS

by JILL

Shin-Ping Tu, M.D., M.P.H.

Francesco S. Celi, M.D., M.H.Sc.

Professor of Internal Medicine Chair, Division of General Internal Medicine

Professor of Internal Medicine Chair, Division of Endocrinology and Metabolism

Joining the medical school last fall, Tu brings both personal and professional experience in cross-cultural medicine. At her previous post at the University of Washington, she worked at a safety-net hospital and studied how to bring evidence-based medicine — particularly preventive medicine — to underserved populations.

Trained in geriatrics and internal medicine, Celi embarked on a project early in his career to study the effects of thyroid hormone on the body’s metabolism — a topic that remains the core of his research. It’s driven both by clinical questions such as why thyroid disease can look completely different between two patients as well as by basic research on identifying the molecular modulators of thyroid hormone.

It’s one thing to say colorectal cancer screening is good and quite another to implement the practice in clinical settings with high staff turnover and culturally diverse patient populations. In a recent study, Tu showed that certain organizational attributes are associated with success in implementing cancer screening at clinics serving Asian Pacific Islanders. She also chairs a CDC/NCI-funded network effort that surveyed Federally Qualified Health Centers for such attributes. Her work represents a key step in translational research — “How do we take interventions shown to work in controlled research settings and apply them to different practice settings?” Tu says she is struck by the talent and passion on the MCV Campus. “It’s similar to the energy and enthusiasm at the startup company my son works at,” she says. “I’m thrilled that General Internal Medicine faculty play a big role in quality improvement efforts — and we have a huge footprint in patient care.”

Celi’s most recent post was at National Institute of Diabetes and Digestive and Kidney Diseases. While there, he conducted a study on the metabolic effects of shivering that attracted quite a bit of press. The body’s response to cold exposure includes release of a hormone called irisin that drives the expansion of heat-generating brown adipose tissue and is similar to what happens during exercise. The East Coast – facing a polar vortex – celebrated the idea they were also losing weight. Celi sees VCU as a very welcoming place to do research at the bench and the bedside. “It’s remarkable how close the integration of research and teaching and delivery of care are here,” he says. As division chair, he looks forward to implementing a comprehensive approach to diabetes care, integrating inpatient and outpatient services and boosting early intervention strategies.

Dionne honored as Alumni Star Pain control in dentistry was focus of 30-year NIH career

In his D.C.-area dental practice in the early 1970s, Raymond Dionne, D.D.S., saw how many patients were afraid to go to a dentist due to their anxiety about the pain of dental procedures. “This resulted in a vicious cycle that resulted in dental neglect leading to caries, periodontal disease and, eventually, acute painful infections and toothaches that required urgent care that was, in fact, much more painful than preventive and restorative procedures that could have prevented the problem.” At the time, dentists combated this with general anesthesia drugs used at doses to produce sedation, despite the lack of evidence they were safe for dental outpatients. Translational research was not yet in vogue, but pharmacology professor William Dewey, Ph.D., and the department’s Ph.D. program backed Dionne’s vision. Accepted as a doctoral candidate in 1975, Dionne embarked on his career-long research strategy to develop a scientific basis for drugs used for pain and anxiety control in dentistry by conducting clinical pharmacology studies of their efficacy and safety.

From the operating room to tiny table saws

“The support and wisdom of Drs. Dewey, Robert Balster and Louis Harris at that pivotal point in my career was essential for the opportunity to pursue the scientific road less traveled, advance to an entry level position at NIH and sustain my

by Nan Johnson

David Chelmow, M.D., chair of the Department of Obstetrics and Gynecology, likes working with his hands. That may come as no surprise for a surgeon, but this one puts his dexterity to use outside of work as well – building model ships. “I love operating, but it’s nice to work on models because I don’t have to worry about pain control and bleeding,” he explains. “It’s much more relaxing!” His enthusiasm for ships and history fuels his projects, which take between four and five years to complete. The latest completed model is that of an American privateer built in 1780 in Plymouth, Mass. “The British were good about making plans of captured vessels, so the only early American ships we can model accurately tend to be the ones that were captured.” Chelmow used the frame and a few gun barrels and anchors from a kit, but made everything else by hand using boxwood, Swiss pear, holly, ebony and cherry woods. Finding time for his varied interests is par for the course for the Leo J. Dunn Distinguished Professor, who’s had a busy few years. After drafting ACOG’s most recent cervical cancer screening guidelines issued in 2012, he helped start a national organization for academic generalist obstetricians and gynecologists and was chosen to be its first president. A book he edited with two VCU colleagues is about to be published. “I’ll have some more time in the coming months,” he predicts. No doubt he’ll spend part of that working with wood and very tiny table saws. > Read more online: http://go.vcu.edu/TableSaws

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Recruits

F. Gerard Moeller, M.D.

Mark G. Malkin, M.D., F.R.C.P.C., F.A.A.N.

Professor of Psychiatry and Pharmacology and Toxicology Chair, Division of Addiction Psychiatry

Professor of Neurology and Director of the Neuro-Oncology Program The William G. Reynolds Jr. Chair in Neuro-Oncology

The first visible effect of Moeller’s arrival was the installation of a new research-dedicated MRI scanner. Moeller, who takes the helm of the Institute for Drug and Alcohol Studies, brings a human research program that will complement the medical school’s traditional strengths in preclinical drug abuse research.

On the MCV Campus, you’ll find all the pieces in place for a strong neurooncology program: neurosurgery, neuropathology, medical and radiation oncology and basic science. With Malkin’s arrival, the final piece is in place. As the region’s only board-certified neuro-oncologist, he’ll pull the components together into a unified program.

Moeller uses MRI to study the neurobiology of behavior, with an eye to developing new treatments for addiction. For instance, cocaine addicted individuals’ brains show changes in white matter — the connections between nerve cells, changes that are associated with impulsivity. “This could be a new target for treatment in people with cocaine addiction,” he says.

It’s a small subspecialty — only about 0.5% of neurologists are board certified in neuro-oncology — but it’s crucial to understand and treat brain tumors, the neurological complications that can accompany chemotherapy (including chemobrain) and cancer metastatic to the nervous system. “Compared to other neurological diseases, brain tumors are relatively uncommon, so many doctors in training don’t get exposure to those patients,” Malkin says. The same is true of oncologists, as the incidence of primary brain tumors is far less than breast, prostate, lung or colon cancer.

The approach is useful for studying other conditions in which impulsivity plays a role, such as traumatic brain injury, attention deficit hyperactivity disorder and binge eating. Joining the medical school is, Moeller says, “A major opportunity for me to collaborate with other VCU researchers in these research areas.” In addition, Moeller is charged with overseeing Addiction Medicine. He looks forward to the challenge of treatment and patient care. Combining clinical duties with research investigation works both ways, he says. Not only does research uncover new avenues for treatment, but clinical work informs the research questions.

In addition to seeing patients and starting a fellowship program, Malkin will spend nearly half of his time on translational research, trying to develop novel ideas into better treatment options. “There’s a lot of really innovative basic science research here just begging to be tested in phase 1 and phase 2 trials,” he says. That’s exactly what he plans to do.

enthusiasm for translating unmet therapeutic needs into scientific inquiry that eventually informs and often results in changes in clinical practice.” In more than 30 years at the National Institutes of Health, Dionne’s research resulted in more than 100 scientific manuscripts on pain and pain control. His findings have yielded several innovative therapies to relieve dental outpatients’ pain and perioperative apprehension. Along the way, he’s identified moleculargenetic targets that could lead to new analgesics as well as brought into question the safety and usefulness of some investigational procedures like the use of deep brain stimulation for intractable chronic pain. He credits “the professional judgment and character of Drs. Dewey, Balster and Harris in taking a gamble on a naïve but well-intentioned young professional. I have endeavored to learn from their example to provide similar opportunities to other trainees. I also hope to follow their continuing example to be professionally active in my golden years. I recently retired from NIH and have joined the pharmacology department at East Carolina University in hopes of contributing to the training of the next generation of clinical/translational investigators to follow in our footsteps.” PHARMACOLOGY ALUMNUS RAY DIONNE, D.D.S., PH.D.’80 (SECOND FROM LEFT), WAS RECENTLY HONORED AS THE SCHOOL OF MEDICINE’S 2013 ALUMNI STAR. HE SAYS HE HAS ALWAYS BEEN GRATEFUL TO DRS. LOU HARRIS, BILL DEWEY AND BOB BALSTER (LEFT TO RIGHT) FOR “THE OPPORTUNITY THAT THE FACULTY PROVIDED FOR ME AT A PIVOTAL POINT THAT LED TO A FULFILLING CAREER AS A CLINICAL PHARMACOLOGIST.”

Pediatrician wins 2-year national grant to study children’s health in Bangladesh Two deadly problems for children living in the developing world are malnutrition and the failure of oral vaccines to protect them against polio and rotavirus. Jeff Donowitz, M.D., an infectious diseases fellow in the Department of Pediatrics, has hit upon a theory that’s won him the support of a two-year fellowship. Donowitz is one of just seven pediatricians in the U.S. selected this year by the Association of Medical School Pediatric Department Chairs for the Pediatric Scientist Development Program. He hypothesizes that a condition known as small bowel bacterial overgrowth could hold answers to both the malnutrition and the vaccine failure seen in infants born into the developing world’s impoverished communities. The small intestine normally contains bacteria. But those with small bowel bacterial overgrowth have abnormally high numbers of our body’s normal bacteria. Those with the syndrome suffer from poor absorption of nutrients, and their immune system may also be compromised, since the gastrointestinal tract houses essential components for healthy immune function. “Your gut’s immune system is the first place to react to an oral vaccine,” explains Donowitz. “Could an unhealthy gut be interfering with the vaccines’ effectiveness?” Because SBBO is treatable with antibiotics, Donowitz’s hypothesis has the potential to improve many aspects of the children’s lives. > Read more online: http://go.vcu.edu/Donowitz

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HONORS& ACCOLADES Cifu named one of Virginia’s Outstanding Faculty David X. Cifu, M.D., was one of 12 faculty members from Virginia’s public and private colleges and universities honored with the 2014 Outstanding Faculty Award from the State Council of Higher Education for Virginia. An internationally renowned researcher in the area of neurologic rehabilitation, he has been funded on 33 federal research grants for more than $110 million since 1992. He is principal investigator for a national research consortium studying what happens to service members and veterans who suffer mild traumatic brain injuries or concussions. Cifu is chairman and Herman J. Flax, M.D., Professor in the Department of Physical Medicine and Rehabilitation and is national director of the Physical Medicine and Rehabilitation Program Office for the Veterans Health Administration. He has more than 200 articles and 65 abstracts to his credit and has co-authored 27 books and book chapters.

Fisher honored as one of state’s outstanding scientists Paul B. Fisher, M.Ph., Ph.D., has been named one of Virginia’s Outstanding Scientists of 2014. He is one of two scientists to receive this year’s award. Virginia Gov. Terry McAuliffe recognized Fisher for his pioneering work in the field of molecular biology and the translation of his research from bench to bedside. Fisher studies the mechanisms involved in cancer development and progression, and the mda-7/IL-24 gene was originally cloned in his lab. The discovery was praised for its potential to impact the lives of countless cancer patients. Fisher is professor and chair of the Department of Human and Molecular Genetics and is co-leader of the Cancer Molecular Genetics research program at VCU Massey Cancer Center. He also holds the Thelma Newmeyer Corman Chair in Cancer Research at Massey and directs the VCU Institute of Molecular Medicine.

Kendler accepts 2013 Thomas William Salmon Award in Psychiatry The New York Academy of Medicine has honored Kenneth Kendler, M.D., with its 2013 Thomas William Salmon Award in Psychiatry. Each year the Academy recognizes a prominent specialist in psychiatry, neurology or mental hygiene for outstanding contributions to these fields. In making its award, the academy noted “Dr. Kendler’s research has truly revolutionized our knowledge of the foundations of mental health. His academic work and translational contributions to the field have set the stage for the next chapters of research and practice in the science of psychiatry.” Kendler is the Rachel Brown Banks Distinguished Professor of Psychiatry and professor of Human and Molecular Genetics.

Kukreja receives international cardiovascular honor Rakesh C. Kukreja, Ph.D., has been honored by the International Academy of Cardiovascular Sciences with its Norman Alpert Award for Established Investigators in Cardiovascular Sciences. The award recognizes Kukreja for work performed throughout his lifetime. For more than two decades, Kukreja’s research has focused on protecting the heart, particularly by studying the mechanisms by which heart attacks kill cardiac cells and developing new therapies to minimize the damage. One of his best-known discoveries was that phosphodiesterase-5 (PDE5) inhibitors including Viagra have a powerful cardioprotective effect against ischemia and reperfusion injury as well as for heart failure and doxorubicin-induced cardiomyopathy in cancer patients. A professor of internal medicine, Kukreja holds the Eric Lipman Chair of Cardiology and serves as scientific director of the VCU Pauley Heart Center.

Wenzel honored by International Federation of Infection Control Richard P. Wenzel M.D., M.Sc., has been named the recipient of the 2014 Martin S. Favero Award of the International Federation of Infection Control. The award honors a lifetime achievement in infection prevention and control worldwide. Wenzel’s body of work includes significant contributions on the epidemiology of hospital-acquired infections, especially bloodstream infections and sepsis. He has authored more than 500 scientific publications and six textbooks, and the journal he founded, Infection Control and Hospital Epidemiology, continues to thrive after 30 years. In 2001, The New England Journal of Medicine named him its first editor-at-large. A professor and former chairman of the Department of Internal Medicine, he has trained more than 50 fellows.

A NATIONAL FRAMEWORK TO IMPROVE HEALTH Alex Krist, M.D., associate professor, and Steven Woolf, M.D., professor, both with Department of Family Medicine and Population Health One of the major problems facing healthcare today is how to bridge the gap between primary care and community support for KRIST disease prevention. Doctors are effective in motivating patients and administering treatment, but are not equipped to provide daily support like that afforded by various community resources. A large portion of Americans fall into what’s termed the prevention gap, receiving preventive measures that are inadequate to promote health WOOLF and save lives. Krist and Woolf focus on closing this gap by integrating and effectively coordinating preventive measures from both clinical and community settings. Through field studies of 53 successful clinicalcommunity integrations, the authors propose a framework for success: a collaboration among federal and academic institutions with necessary community input to effectively support a healthier lifestyle, prevent disease and ensure successful treatment on a broad scale. “With national efforts to not only expand coverage of clinical preventive services, but to test innovations for promoting quality health care as well, developing and implementing new clinical-community integration models such as the framework we have created is of critical importance to improve the health of Americans,” said Krist. American Journal of Preventive Medicine, October 2013

-AKD WIDOWS, WIDOWERS ‘EMOTIONALLY INOCULATED’ AGAINST CHRONIC PAIN  James B. Wade, Ph.D., professor of psychiatry  Widowed chronic pain patients experience less emotional suffering and greater psychological hardiness when faced with lifestyle stress, such as physical pain, than their married, divorced, separated or single counterparts. “My patients often share with me their anxiety about having to go it alone after the loss of their loved one,” said Wade. “This study identifies good news regarding how the elderly successfully cope with life’s challenges on their own, and the findings speak to the strength of the human spirit to recover and to develop new psychological strength after misfortune.” The research team evaluated 1,914 chronic pain patients. Those subjects who had experienced the death of a spouse suffered significantly less frustration, fear and anger than subjects in all other marital categories, and less depression and anxiety than divorced individuals. Both widow and widower derived the same psychological hardiness from having endured the painful loss of a spouse. The researchers concluded that, after experiencing the death of a spouse, an individual may derive some form of “emotional inoculation” that serves to protect them against future lifestyle threats. Pain, Research and Treatment, August 2013

DRUG COMBINATION THERAPY CAUSES CANCER CELLS TO “EAT THEMSELVES” Paul Dent, Ph.D., professor of biochemistry and molecular biology and the Universal Corporation Chair in Cancer Cell Signaling at Massey Results from a preclinical study have shown that a new drug combination therapy effectively killed colon, liver, lung, kidney, breast and brain cancer cells while having little effect on noncancerous cells. The study combined the drugs sorafenib and regorafenib with a class of drugs known as PI3K/ AKT inhibitors. Sorafenib and regorafenib block the production of enzymes called kinases, which are vital to the growth and survival of cancer cells. However, they

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by Erin Lucero and Anish K. Desai

do not directly affect PI3K and AKT kinases, which are very active in promoting cancer cell survival. That led the researchers to add a PI3K/AKT inhibitor. The result was a dramatic increase cell death even against cells with certain mutations that make one or the other drug less effective. “We know that certain cellular processes are frequently dysregulated in cancers and important to cell proliferation and survival, but if you shut down one, then cells can often compensate by relying on another,” says Dent. “We are blocking several of these survival pathways, and the cancer cells are literally digesting themselves in an effort to stay alive.” Researchers plan a future phase 1 clinical trial to test the safety of the therapy in a small group of patients. Molecular Pharmacology, published online before print July 22, 2013.

-AKD ENGAGING PATIENTS WITH THEIR PERSONAL HEALTH RECORD John William Kerns, M.D., clinical professor with the Department of Family Medicine and Population Health’s Shenandoah Family Medicine Residency Program Personal health records (PHRs), digital and accessible by patients and clinicians alike, are an important tool for patient-centered care, but only a fraction of Americans use them. The Department of Family Medicine and Population Health conducts research on PHRs using a web site they’ve developed, MyPreventiveCare.com. Kerns and his colleagues investigated what factors are important for engaging primary care patients with a PHR. They discovered that even advanced healthcare technology does not trump the patient-clinician relationship. Patients are more confident that their information would be accurate, secure and private if the PHR was used by their physician. Further, they were more likely to access their PHR if the invitation to do so was closely timed to an appointment and relevant to the patients’ health concerns. Then the technology not only improved the care patients received, it enhanced the interactions between patients and clinicians. “Given the national investment of $27 billion to promote the adoption, implementation and meaningful use of health information technology, it is essential to understand how to better engage patients in using technology if it is to achieve its full potential,” Kerns wrote. “Many Americans have not embraced the use of PHRs, but our findings underscore the general interest of patients in using such tools if certain attributes are offered,” especially in the context of the patientclinician relationship. BMJ Open, July 2013

-AKD GENETIC ARCHITECTURE OF BRAIN’S GREY MATTER COULD PROVIDE CLUES TO NEUROPSYCHIATRIC DISORDERS Michael Neale, Ph.D., professor of psychiatry and human & molecular genetics An international research team has found that genetic factors may affect the varying thickness of different parts of the cortex of the brain. A better understanding of the complex structure of the human brain and the underlying genetic factors could eventually help identify individuals at risk for neuropsychiatric disorders such as autism, schizophrenia, depression or dementia. Led by researchers at the University of California, San Diego, the team used innovative software developed by Neale. With data from MRI brans scans of 200 twins, the software drew a genetic correlation map based on cortical thickness at thousands of points on the surface of the brain. These correlations were then analyzed to identify regions where the same genetic factors seem to have been operating. According to Neale, using twin pairs for the study helps differentiate genetic from environmental factors. Traditionally, maps of the human brain are based on its anatomy or function. The new research builds on the research team’s work published last year in Science

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that was considered the first map of the surface of the human brain based on genetic information. Proceedings of the National Academy of Sciences Online Early Edition, October 2013

-AKD LIVER ENZYME MAY PLAY CRITICAL ROLE IN ENHANCING CHOLESTEROL REMOVAL FROM THE BODY Shobha Ghosh, Ph.D., professor of internal medicine An excess of cholesterol is a wellknown cause of heart disease, and the liver is key to keeping levels in check. In addition to making a large portion of the body’s naturally occurring cholesterol, the liver also regulates cholesterol levels and is the only organ in the body able to remove cholesterol. In a pair of recently published studies, Ghosh describes how a key enzyme in the liver called CEH is critical to that process. By cooperating with the liver receptor for HDL (the “good cholesterol” that carries excess cholesterol back to the liver), CEH helps catalyze important biologic processes and increases the conversion of HDL-cholesterol to bile acids for removal from the body. “Understanding the cellular processes that regulate the removal of cholesterol is important for developing new drugs that can enhance this process,” Ghosh said. “Drugs developed to increase the activity of this enzyme will reduce the deposits of cholesterol in the artery walls. That’s known as atherosclerosis and is an underlying cause of coronary artery or heart disease.” Toward that goal, Ghosh’s laboratory also has discovered that increasing the CEH enzyme in the liver reduces heart disease. Ghosh’s team will now work to further understand the regulation of the enzyme and develop new strategies to increase CEH activity by pharmacological means. Journal of Lipid Research, studies first appeared online in August 2013 and February 2014

PAIR OF PRE-CLINICAL STUDIES SHED LIGHT ON BATTLING MULTIPLE MYELOMA Steven Grant, M.D., professor of internal medicine, the Shirley Carter Olsson and Sture Gordon Olsson Chair in Cancer Research and associate director for translational research at the Massey Cancer Center Pre-clinical evidence that a class of experimental agents known as cyclin-dependent kinase (CDK) inhibitors could improve the effectiveness of existing cancer therapies has led to a number of phase I/II clinical trials. What is not well understood are the mechanisms by which such agents act. In Molecular Cancer Therapeutics, Grant published his discovery that the CDK inhibitor dinaciclib disrupts a cell survival mechanism known as the unfolded protein response. That response is of great interest to cancer researchers because, without the UPR, various malignant cell types, including multiple myeloma and myeloid leukemia cells, become significantly more vulnerable to damage caused by anti-cancer agents. While CDK inhibitors are known to interfere with the division and duplication of cells, recent evidence suggests that they may act through other mechanisms to induce cancer cell death. In a separate study published in the journal Cancer Research, Grant combined another CDK inhibitor, flavopiridol, with the experimental drug obatoclax. Combined therapy resulted in a dramatic increase in multiple myeloma cell death, with each drug working through different but complementary mechanisms to promote a form of cell suicide known as apoptosis. “This research builds on nearly a decade of work carried out by our laboratory that focuses on manipulating mechanisms that lead to apoptosis in blood cancers,” says Grant. “Our findings could have immediate implications for the design of clinical trials using combinations of these classes of agents. In fact, plans to develop such a trial at Massey are currently underway.” Cancer Research, published online in August 2013; and Molecular Cancer Therapeutics, published online on December 20, 2013

SCIENTIFIC FORUM CELEBRATES ITS 30TH YEAR

Each year, the medical school hosts the Daniel T. Watts Research Poster Sym posium to showcase graduate student research and honor the legacy of the first Dean of the Sch ool of Basic Sciences and Graduate Studies. Last October, nearly 40 posters were presented by graduate students and postdoctoral scholars from across VCU, with heavy representation from the bas ic science departments on the MCV Campus. A nationally recognized pha rmacologist, Watts’ work included projects to det ermine human tolerance to the acceleration forces experienced in aviator ejection seats. He wa s recruited to campus in the mid-1960s and charge d with upgrading the basic science research streng ths and the scope of doctoral education. Over the course of 15 years, he was given the resources to hire new chairs in the Basic Science departme nts with additional resources to expand the lev el of research, the number of faculty and the num ber of trainees. Throughout his tenure, the number of Ph.D. graduates increased steadi ly, placing the school among the most productive in the U.S. and lifting it to national prominence. Watts retired as Dean of Bas ic Health Sciences in 1982, and two years later gra duate student poster day was instituted.

SMARTPHONE APP IS VALID TOOL TO SCREEN FOR MINIMAL HEPATIC ENCEPHALOPATHY Jasmohan Bajaj, M.D., associate professor of gastroenterology, hepatology and nutrition Patients with cirrhosis often experience cognitive dysfunction, known as minimal hepatic encephalopathy (MHE) that impairs their quality of life, employment and driving ability. Patients are also at higher risk for progressing to overt hepatic encephalopathy, but treatment has not been standard in the U.S. partly because MHE has been difficult to diagnose. Bajaj developed a free smartphone application that incorporates what’s known as the Stroop task. Patients’ psychomotor speed and cognitive flexibility is evaluated through their identification of various combinations of ink colors and words. To determine the validity of EncephalApp_Stroop app, Bajaj and his team recruited 126 patients with cirrhosis who underwent a battery of recommended cognitive tests including the traditional MHE test and the Stroop app evaluation. The team concluded that the Stroop app reliably screens for MHE. It has the potential to make screening easier and faster and, subsequently, increase treatment rates for affected patients. “This app can be used to rapidly select which patients are likely to benefit from further MHE testing and potential treatment,” said Bajaj. “It can be translated into practice by clinic assistants, nurses or other nonMD professionals to add a cost-effective approach to the rapid diagnosis of MHE.” Hepatology, September 2013


Dean’s Discovery Initiative

NONPROFIT ORGANIZATION U.S. POSTAGE PAID RICHMOND VA PERMIT NO. 869

School of Medicine Development Office VCU’s Medical College of Virginia Campus P.O. Box 980022 Richmond, VA 23298-0022

Volume 13, Number 1 The Dean’s Discovery Report is published twice a year by Virginia Commonwealth University’s School of Medicine on the Medical College of Virginia Campus. Reader comments and suggestions are welcome; please call (800) 332-8813 or (804) 828-4800, e-mail MedAlum@vcu.edu or write to P.O. Box 980022, Richmond, VA 23298-0022.

ADDRESS SERVICE REQUESTED

The Dean’s Discovery Initiative provides an opportunity for donors to transform the research environment in the School of Medicine. Through philanthropy, alumni and friends can support the school’s research endeavor in ways that traditional funding sources do not. Dean: Jerome F. Strauss III, M.D., Ph.D. Produced by the School of Medicine’s Alumni and Development Office: Associate Dean for Development, Tom Holland; Editor, Erin Lucero. Contributing Writers: Jill U. Adams, Anish K. Desai and Nan Johnson Photographers: Allen Jones, Thomas Kojcsich, Kevin Schindler, Jay Paul and VCU Creative Services Graphic Design: Zeigler/Dacus © Virginia Commonwealth University, 2014.

Cardiologist and cancer survivor finds new mission

by Nan Johnson

> Protecting the heart against cancer treatments’ effects

At

first, Michael Hess, M.D., didn’t realize how unusual his idea was.

“Over dinner with colleagues at a professional conference, I cavalierly said, ‘I’ve started a cardio oncology program dedicated to the complications and side effects of cancer treatment on the heart.’ For the next two days, that’s all anybody talked about,” he said. “They thought it was something tremendously novel, but I said, ‘Wait a minute, we’ve been doing it for two years!’” Hess’ concept of cardiology and oncology teams working in tandem is a direct result of a seemingly little known fact. “Very few recognize the correlation between cancer treatments and the development of cardiovascular disease. It’s a leading cause of death among cancer survivors.”

PREVENTING CHEMOTHERAPY’S DAMAGE TO THE HEART IS ONE OF THE GOALS OF RAKESH KUKREJA, PH.D., SCIENTIFIC DIRECTOR OF THE PAULEY HEART CENTER. THIS CONFOCAL MICROSCOPE IMAGE ILLUSTRATES HIS TEAM’S DISCOVERY THAT VIAGRA CAN BOOST THE EFFECTIVENESS OF THE CHEMOTHERAPY DRUG DOXORUBICIN WHILE ALLEVIATING DAMAGE TO THE HEART AT THE SAME TIME.

Not only are aging patients predisposed to develop cardiovascular disease in the first place, but the chemotherapy and radiation treatments that saved their lives is associated with irreversible heart damage, often presenting several years after treatment stops. Hess brings an unusual perspective to the table. Not only is he director of the Cardiology Oncology Program at Pauley Heart Center, he’s a cancer survivor himself. His commitment to the ongoing health of cancer survivors has grown into one of the leading cardio oncology programs in the country. The program’s clinical care is complemented by Pauley Heart Center research that’s geared toward prevention.

MCV Foundation School of Medicine

In 2010, the journal Proceedings of the National Academy of Sciences touted an unexpected finding. In pre-clinical studies, Rakesh C. Kukreja, Ph.D., the Eric Lipman Research Professor in Cardiology, and his colleagues combined the erectile dysfunction drug Viagra with the chemotherapy drug doxorubicin. They discovered that Viagra enhanced doxorubicin’s effectiveness against tumors while alleviating damage to the heart at the same time. Researchers at VCU’s Massey Cancer Center are now studying the drug combination in clinical trials.

In the case of today’s cancer survivors, the challenge becomes protecting the heart against further damage. Knowing the patient’s history, of course, is essential. “Our program recognizes the need for long-term follow up and knowledge of a cancer survivor’s treatment history,” Hess said. “We have to look at history to see what these patients – including me – have been through. It’s a mission of mine.”

Serving the Medical College of Virginia Campus of Virginia Commonwealth University since 1949 and proud to be a partner with the School of Medicine.

PO Box 980234 Richmond, VA 23298 (804) 828-9734 www.mcvfoundation.org


DDR Spring 2014