Dean's Discovery Report Fall 2013

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VOLUME 12, NUMBER 2

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Partners for Discovery

Pauley Heart Center Campaign Launches

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Cardiologist is Hall of Fame Inductee

Program is Buoyed by Philanthropic Gifts and Research Grants

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$20-million campaign in support of the Pauley Heart Center was announced with news that a $5-million leadership gift was already in hand. The gift was made by the Pauley Family Foundation that, in 2006, gave its first $5-million gift to the VCU Medical Center’s cardiology program, which was later renamed the Pauley Heart Center.

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New Recruits

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KL2 Scholarships Support Junior Investigators

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Inaugural Rao R. Ivatury Trauma Symposium

“This is a project that is near and dear to my heart,” said Stanley Pauley, a former patient, who oversees the Foundation along with his wife, Dorothy, and daughters, Katharine Pauley Hickok and Lorna Pauley Jordan. “The care these health care professionals provide is so genuine and moving that it is an honor to contribute to research that will enable them to learn even more about heart disease.”

Their generosity has already brought about significant improvements to the care patients receive, said Cardiology Chair Kenneth Ellenbogen, M.D. “The Pauleys’ gift has transformed our facility into a first-tier heart center by allowing us to devote resources towards renovating and improving our research laboratories.”

The Pauleys’ $5-million gift will be matched by funds from the Glasgow Endowment, resulting in a total of $10 million for the heart program. Established in the 1950s shortly before the deaths of Arthur Glasgow and his wife, Margaret, the Glasgow Trusts disbursed in 2011, following the death of the couple’s last heir. The portion of their estate bequeathed to VCU totaled $45 million.

With the help of a match from the Glasgow Endowment, a $500,000 gift from an anonymous donor will establish an endowed chair honoring George Vetrovec, M.D., professor of medicine and director of the Adult Cardiac Catheterization Laboratory.

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Research Notes

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$62 Million Traumatic Brain Injuries Study

LONGTIME SUPPORTERS OF THE CARDIOLOGY PROGRAM, STANLEY AND DOROTHY PAULEY HAVE MADE A $5-MILLION LEADERSHIP GIFT THAT LAUNCHES A $20-MILLION CAMPAIGN IN SUPPORT OF THE PAULEY HEART CENTER.

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Grateful patient John R. Congdon, Sr., has been a generous donor in the past to the Massey Cancer Center as well as to the Pauley Hear Center. His recent $500,000 gift was matched dollar-fordollar to establish the Natalie N. and John R. Congdon Sr. Endowed Chair.

ADDITIONAL CAMPAIGN

GIFTS

A lecture series to support and advance education in heart failure was established by Frances Crutchfield in memory of her husband, George. With her $100,000 gift, she also honored Michael Hess, M.D., chairman of the Division of Cardiopulmonary Laboratories and Research, who cared for her husband for more than 30 years.

New Research Grants Support Center’s Work , Since 1972, MCV Campus cardiology researchers have benefitted from the support of the American Heart Association’s national center and Mid-Atlantic Affiliate. In the latest round of funding, AHA MidAtlantic supported 12 research projects with $2.4 million in grant funding, bringing the 40-year total to $12.8 million.

In the tradition of the Medical College of Virginia

The AHA has a history of providing start-up funding for investigators who are new to the field. That’s where Rakesh Kukreja, Ph.D, found himself in 1987 when he received his first AHA grant. “It was the turning point of my career. The grant gave me confidence to do further research. It has been the seed money to help me build my profession and develop novel strategies to improve heart health.”

Now the Eric Lipman Professor in Cardiology, Kukreja serves as scientific director of the VCU Pauley Heart Center. He also has his own active research program, recently securing $2.6 million from the National Institutes of Health to study new strategies for protecting the diabetic heart against injuries caused by heart attack.

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School of Medicine

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PARTNERS for DISCOVERY Lending support to faculty, new discoveries

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MOLECULAR MEDICINE: TAKING AIM AT CANCER Each year the Prostate Cancer Foundation bestows its $1-million A. David Mazzone Challenge Award to a large-scale innovative research project in the area of prostate cancer. In 2012, the award went to a team of researchers: Department of Human and Molecular Genetics Chair Paul B. Fisher, M.Ph., Ph.D., and his two colleagues at Johns Hopkins University, Martin G. Pomper, M.D., Ph.D., and George Sgouros, Ph.D.

Findings from his National Cancer Institute-supported study were published in the July 2013 issue of the International Journal of Cancer. The report describes how mda-7/IL-24 directly impacts two forms of cell suicide known as apoptosis and toxic autophagy, regulates the development of new blood vessels and also plays a role in promoting the immune system’s cancer-fighting ability in the whole cancer population as well as in cancer-initiating stem cells.

The trio of researchers is working together on developing “theranostic” nanoparticles – so named for their dual role in providing diagnostics and therapeutics. In the case of Fisher and Pomper’s nanoparticles, they deliver molecular-genetic imaging of prostate cancer cells along with drugs to eliminate them.

“Our lab is developing several promising viral gene therapies to deliver the mda-7/IL-24 gene that have been shown to kill cancer cells at the original tumor site and also in distant metastases,” Fisher said. “This therapy may someday be an effective way to eradicate both early and advanced stage breast cancer, and could even be used to reduce the risk of cancer recurrence by eliminating cancerinitiating stem cells.”

The work got its start when Fisher’s lab isolated a gene promoter called PEG-Prom that is activated in cancer cells, but not normal cells.

Using PEG-Prom, the researchers are able to deliver avidin, a protein produced by birds that, in effect, paints a target on the surface of prostate cancer cells to increase the power of radiation therapy to destroy those cells.

“Using avidin in this modified two-step ‘pre-targeting’ process is a novel strategy that holds high potential to develop a systemic therapy for prostate cancer,” said Fisher, who also holds the Thelma Newmeyer Corman Chair in Cancer Research and is the director of the VCU Institute of Molecular Medicine.

At any given time, Fisher’s laboratory is pursuing as many as six different research projects. Another promising avenue for investigation has been a gene known as mda-7/Interleukin-24 (mda-7/IL-24) that was originally cloned in Fisher’s lab.

The cover of the September 1, 2013 issue of the journal Clinical Cancer Research features Fisher’s work on the gene MDA-9/Syntenin that is associated with cancer metastasis.

Reprinted by permission from the American Association for Cancer Research: Paul B. Fisher, Novel Role of MDA-9/Syntenin in Regulating Urothelial Cell Proliferation by Modulating EGFR Signaling, Clinical Cancer Research, September 1, 2013, Vol. 19, Num. 17.

NEWLY FUNDED PROJECT COULD INCREASE STROKE PREVENTION IN RICHMOND AND BEYOND Pfizer Inc. has awarded VCU’s Institute for Women’s Health a competitive medical education grant to support the Virginia Women’s Stroke Prevention Initiative. The project launches a comprehensive strategy to promote the prevention of stroke in women with a focus on underserved women.

Women are more likely than men to have a stroke. Though stroke kills twice as many women as breast cancer every year, less than a third of women could name more than two of stroke’s six primary symptoms, according to the National Stroke Association.

“Stroke is the third-leading cause of death in the United States,” said Warren L. Felton III, M.D., a professor of neurology and the medical director of the VCU Stroke Center. “Ultimately, this study will serve to reduce the risk of stroke in both women and men served by VCU Medical Center and throughout Virginia.”

Felton is principal investigator on the two-year project that totals nearly $700,000. Co-principal investigator on the grant is Susan Kornstein, M.D., executive director of the Institute for Women’s Health and a professor of psychiatry, obstetrics and gynecology.

“This project is important for helping to educate both patients and health care providers about unique health issues for women with regard to stroke prevention,” Kornstein said. “The project will use our electronic health record to improve identification and manage risk factors for women who are at increased risk of stroke.”

The initiative will put in place risk screening and evidence-based treatment guidelines using the electronic medical health record that is available in primary care clinics at the VCU Medical Center. Additional patient education will be offered through the medical center’s Community Health Education Center.

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Cardiologist is Hall of Fame Inductee On a rugby playing field, there’s just one referee. There are 30 players of varying sizes and strengths. But just one man, carrying a whistle, charged with making sure the game is played according to the sport’s laws. That’s right. Laws.

It’s a role in which John V. “Ian” Nixon, M.D., excelled. So much so, in fact, that he was inducted into the U.S. Rugby Hall of Fame this summer.

For more than a decade, Nixon traveled the world refereeing dozens of high-profile international match-ups. He was America’s first international referee and, at his retirement in 1987, the country’s highest ranking – a position he held for seven years running.

While he counts it an honor that his Hall of Fame election was voted on by respected colleagues, he says, “The memories are what count. That and your enjoyment of it.”

His love of the game got its start in his native England. He caught his first rugby pass when he was eight and went on to play for nearly 30 years, earning the position of scrumhalf, akin to the quarterback in football.

While in Boston, he became interested in echocardiography.

Then in its infancy, the noninvasive technology held the potential to give cardiologists a moving picture of the heart.

It would be the cornerstone of his career, first in Dallas at the University of Texas Southwestern Medical Center and later at VCU. Over the past 40 years, he says, “the technology has grown more sophisticated and more common.”

When he arrived on the MCV Campus in 1986, the hospital did 1,450 procedures a year. Now it’s up to 12,000.

For more than a decade, Ian Nixon, M.D., America’s first international rugby referee, traveled the world refereeing dozens of high-profile international match-ups. This summer, he was inducted into the U.S. Rugby Hall of Fame.

His affinity for sports didn’t end on the rugby field. He’s written and lectured on the athletes’ heart, and he’s conducted studies on heart function in athletes. Findings from those and other studies have resulted in the publication of more than 130 original papers, book chapters and review articles.

Throughout his playing and refereeing days, he’d re-set the occasional dislocated finger.

But few on the field knew he was a physician.

He may be best known as the two-time editor of “The AHA Clinical Cardiac Consult Book” reputed for fast, reliable guidance on the diagnosis and management of cardiovascular problems. His stellar work on the project resulted in the American Heart Association recognizing him with its Award of Meritorious Achievement.

In 1972, he immigrated to the United States, securing a prestigious cardiology fellowship at Harvard Medical School and the Brigham and Women’s Hospital in Boston. There he trained with Richard Gorlin, M.D., famed for developing a formula still considered the gold standard for evaluating the severity of valve stenosis.

Today a professor of internal medicine and director of the Cardiovascular Imaging and Noninvasive Cardiology, Nixon says he still calls on skills he learned on the rugby field. As a referee, he prided himself on his game and player management, developing a rapport with the teams that he could use to defuse conflict.

Game photo courtesy of John Duval, CEO of MCV Hospitals, who played with West Coast rugby clubs in the 1970s and 80s.

Go online to learn who else has rugby connections. http://go.vcu.edu/RugbyRoster

He was known for his deft management of people under stress. “It’s two 40-minute halves of continuous play. The physiological demands are enormously high.” He compares it to managing medical personnel in critical situations: “When they are exhausted, fuses are shorter, concentration is more fixed.”

Those skills paved the way for Nixon’s Hall of Fame election. Nixon is among just the third class of inductees. His level of service to the sport sets him apart, having also served two terms as president of the United States of America Rugby Football Union.

Now he limits his involvement to that of spectator. He’s eagerly anticipating the 2016 Olympics in Rio de Janeiro. After all, he points out, the USA has to defend the Olympic gold it won the last time rugby was played – in the Paris Olympics, back in 1924.

Charles (Chuck) V. Clevenger, M.D., Ph.D. Chair of the Department of Pathology and the Carolyn Wingate Hyde Endowed Chair of Cancer Research* LAST POST:

NORTHWESTERN UNIVERSITY FEINBERG SCHOOL OF MEDICINE

by Jennifer C. Usher

A pathologist who specializes in breast cancer, Charles V. Clevenger, M.D., Ph.D., was drawn to take the post as chair of the Department of Pathology because of its tradition of clinical excellence. “It was attractive to me that it’s already an outstanding clinical department that has strong leadership across the board, so I can focus on building up other areas like research, translation and outreach,” he says.

Joining the medical school also gave Clevenger the opportunity to reunite with a valued colleague: Dean of Medicine Jerry Strauss III, M.D., Ph.D. “He was an informal mentor to me back when we were both on the faculty at the University of Pennsylvania School of Medicine,” Clevenger says. “I developed a high level of trust and respect for him there, and we kept in touch over the years.”

Prior to arriving on the MCV Campus in August, Clevenger was the Diana, Princess of Wales Professor of Cancer Research in the Department of Pathology at Northwestern University. There he led an NIH-funded translational research program on women’s cancer and was the co-leader of the Avon Foundation Breast Cancer Research Laboratories.

His research focuses on prolactin, a hormone that stimulates breast development and milk production in women and can also stimulate the growth of breast cancer.

Clevenger led his research team in making key discoveries about prolactin’s role in the growth and spread of breast cancer.

Now he is developing novel therapies aimed at blocking either the release or the function of prolactin to stop it from promoting growth and metastasis. These therapies include repurposing well-known drugs, such as Cabergoline and Cyclosporine A, both of which are now being examined in phase I and II trials in patients with breast cancer.

In addition to continuing these investigations and recruiting students and postdocs to join his lab, Clevenger says he hopes to help expand the ongoing basic research efforts in the Department of Pathology with an emphasis on cancer biology. “I’m looking forward to building both the department and my lab and collaborating with the faculty, staff and students,” he says.

Currently, Clevenger serves as a member of the editorial board for Breast Disease, and in 2003 he received the Pfizer Outstanding Investigator Award from the American Society for Investigative Pathology.

Charles (Chuck) E. Geyer, Jr., M.D., F.A.C.P. Associate Director of Clinical Research at the Massey Cancer Center, Professor in the Division of Hematology, Oncology and Palliative Care in the Department of Internal Medicine and the Harrigan, Haw, Luck Families Chair in Cancer Research* LAST POST:

THE UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER AND THE STATEWIDE CLINICAL TRIALS NETWORK OF TEXAS

In his role as associate director for clinical research at the Massey Cancer Center, Charles E. Geyer, Jr., M.D., F.A.C.P., oversees the development of oncology clinical trials. It’s a role he is uniquely suited for because of his expertise in designing and conducting clinical research studies.

Most recently, he was the president and chief medical officer of the CTNet, a research collaboration of academic and community-based cancer centers across Texas. Prior to that, he oversaw development and conduct of clinical studies as the director of medical affairs at the National Surgical Adjuvant Breast and Bowel Project in Pittsburgh. In addition, he was the founding co-chairman of the National Cancer Institute’s Breast Cancer Steering Committee, which reviews and prioritizes phase 3 and large phase 2 research trials.

Now Geyer will direct his attention to expanding Massey’s participation in multi-center trials launched by groups like the NSABP. He’ll also develop infrastructure to support Massey researchers in rapidly translating their own laboratory discoveries into new clinical trials. “We’ll be collaborating more with community oncologists because we want to take the promising discoveries of VCU scientists and offer them quickly to patients across the state through

a vibrant clinical trials network,” he explains. “I’m excited by the strong commitment at Massey and the VCU School of Medicine to enhancing and expanding the clinical research program.”

Geyer’s own research focuses on treatments for HER2positive breast cancer. In women with this cancer, a genetic mutation causes breast cancer cells to make too much of a protein called human epidermal growth factor receptor 2 (HER2) that causes the cancer cells grow and divide faster.

Geyer has led studies that paved the way for the FDA’s approval of drugs that block the effects of the HER2 protein. He served as co-lead investigator on the pivotal Tykerb trial and was a lead investigator in the landmark clinical trial that showed the breakthrough drug Herceptin added to chemotherapy was more effective than standard chemotherapy alone in early stage HER2-positive breast cancer.

Geyer currently is co-chair of the scientific steering committee for a new global trial looking at using the recently approved drug for resistant HER2 positive metastatic breast cancer, Kadcyla, as an alternative to Herceptin in women with resistant HER2-positive early stage breast cancer.

*expected academic investiture in fall 2013

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Among the dozen projects recently funded by the AHA is one led by Antonio Abbate, M.D., Ph.D. The assistant professor of internal medicine studies drugs that prevent damage that occurs to the heart over time following a heart attack. He recently published results in the American Journal of Cardiology from studies of the anti-inflammatory drug anakinra.

ELLENBOGEN

“In these pilot studies, we found that anakinra quenched the inflammation in the heart during acute myocardial infarction and appears to prevent heart failure,” said Abbate.

Research in the Pauley Heart Center is bolstered by a recent renovation to its research laboratories. Funded in part by a $5-million NIH grant, the renovation includes a 3,000-square-foot expansion that’s been outfitted with a cold room for experiments requiring frigid conditions and a dark room to track fluorescent proteins.

The Pauley Heart Center Campaign

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The ongoing $20-million campaign will support recruiting a scientific director and five new research faculty members, along with start-up funds for lab research staff and equipment. The campaign goals are built around the need for new research programs in disease prevention, women’s cardiovascular health and congenital heart disease. In addition, funds will be targeted to accelerate existing nationally acclaimed programs in cardio-protection research, ARCTIC resuscitation for cardiac arrest and artificial devices such as Total Artificial Hearts.

Up to $5 million from the Glasgow Endowment is available to match eligible gifts of at least $500,000. For more information, contact Lauren Moore, senior development officer, at (804) 828-4100 or lzmoore@mcvh-vcu.edu.

ABBATE

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KL2 Scholarships Support Junior Investigators Junior faculty building careers in clinical and translational research find a resource in VCU’s Center for Clinical and Translational Research. In the spring, the center announced five medical school faculty members are among a new cadre of KL2 Scholars who’ll receive substantial salary support and dedicated time to pursue clinical and translational research projects. The scholars also get the benefit of a mentoring team of experienced clinical and translational researchers as they pursue independent research programs in a variety of areas.

Anshu Gupta, M.D. assistant professor Department of Pediatrics

Gupta will spend her KL2 scholarship researching cardiometabolic disease, which is an umbrella term for the risk relationship between cardiovascular disease and diabetes. > “The KL2 scholar award provides me with a unique opportunity to train as a clinical translational researcher with a diverse team of mentors across multiple disciplines. The award truly reflects on the rich, transdisciplinary, collaborative environment that VCU provides to investigators at all levels of their careers, especially early stage investigators like me.”

April Kimmel, Ph.D.

Penetrating Injury Discussed at Inaugural Rao R. Ivatury Trauma Symposium

assistant professor Department of Healthcare Policy and Research Kimmel will examine the geographic variation in HIV treatment and access to care in the United States. Her research interests include models of care delivery for HIV/AIDS, global health and population ethics. > “As a junior investigator, protected time in which to conduct research is critical to my professional development. The KL2 award supports this time and is allowing me to establish a new line of research. This program has allowed me to formalize involvement with a diverse, committed mentoring team, and it provides ready access to institutional resources that will enhance my research skills.”

Margaret Park, Ph.D.

research assistant professor Department of Biochemistry and Molecular Biology Park will investigate the global RNA splicing changes that occur as a result of metastasis in breast cancer. The hope is to translate the findings into identifying prognostic indicators for metastatic cancer. > “The first step towards independence is an important event in the career of any research scientist. Being a recipient of the KL2 scholarship allows me both the freedom to pursue my own research interests, and the opportunity to receive mentoring and career-related guidance from an outstanding team of more experienced scientists. Overall, the KL2 scholars program is a wonderful opportunity to increase research independence for junior faculty.”

Nicole Rankins, M.D.

assistant professor Department of Obstetrics and Gynecology Rankins will look at the contributory factors to gestational weight gain with a focus on overweight and obese pregnant women as her KL2 research project.

Her overall research interests include improving maternal and fetal outcomes and utilizing pregnancy as a window of opportunity for improving long-term maternal and children’s health. > “The KL2 program is an exceptional opportunity for me as a junior investigator. It provides the time, resources, environment and mentoring that are necessary to facilitate my transition to an independently-funded physician-scientist.”

Carlos Villalba Galea, Ph.D. assistant professor Department of Physiology and Biophysics

Villalba Galea will spend his time as a KL2 scholar investigating the biophysical properties of the tumor-suppressing enzyme known as PTEN. Mutations of PTEN are a step in the development of many cancers, therefore understanding the effect of these mutations is critical for the development of therapies to treat PTEN related illnesses. > “Being a basic scientist, I am very excited and honored to be a KL2 scholar. This is a great opportunity that opens the door to the world of translational research. I believe that being a KL2 scholars brings a once-in-a-lifetime chance to harness our experiences and knowledge and search ways to readily apply them to the everyday clinical practice, and therefore make accessible to the community what we have harvested from lab benches.”

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The inaugural Rao R. Ivatury Trauma Symposium in May brought leading experts in trauma care from around the country together to discuss “The Good, the Bad and the Ugly” of penetrating injuries.

The Division of Trauma, Critical Care and Emergency Surgery hosts the symposium each year, but re-named it in 2013 to mark the retirement of Ivatury from his position as division chair, a post he had held since 1998. During his tenure, he also served as the program director for the paramedic training program and the surgical critical care fellowship.

“Dr. Ivatury elevated the VCU trauma program to new heights in national and international academic recognitions,” said Michel Aboutanos, M.D., M.P.H., who is Ivatury’s successor as division chair. Aboutanos as well as the symposium’s speakers are mentees of Ivatury.

“The keynote speakers were all leaders in national and international care that have worked extensively with Dr. Ivatury in various national and international trauma societies to improve trauma care in the United States, as well as internationally,” Aboutanos said. “Each is considered a giant in the field of trauma and feel privileged to have benefitted from his extensive contributions to the field of critical care. His work and advice have served each of these giants in their own institutions.”

The symposium’s speakers covered penetrating injuries to the neck, chest and abdomen as well as penetrating peripheral vascular trauma, advocacy strategies for gun control and even a presentation on trauma care in 1861 with a look at the changes in triage and care that came about as a result of the Civil War.

by Jill U. Adams

Two Notable New Grants Target Intractable Health Concerns Preterm births cost the American health care system more than $26 billion annually. Saba Masho, M.D., Dr.P.H., associate professor of Family Medicine and Population Health, will lead a more than $1-million grant to examine the effectiveness of the MASHO Centering Pregnancy program compared to other prenatal care approaches. Funded by the Centers for Medicare and Medicaid Services, the Strong Start for Mothers and Newborns initiative will examine measures including the number of preterm births, the health outcomes of pregnant women and newborns and the cost of medical care during pregnancy, delivery and over the first year of life.

“The findings of this project will have wider health care and policy implications,” said Masho, who is an expert in health disparities and comprehensive care for underserved pregnant women. She will work with four sites around the state that care for high risk Medicaid or Children’s Health Insurance Program beneficiaries.

Cigarette smoking is the leading preventable cause of death in the United States, yet nearly 50 million Americans continue to smoke. While many smokers say they want to quit, currently approved therapies are not successful in every smoker.

BRUNZELL Darlene Brunzell, Ph.D., associate professor of Pharmacology and Toxicology, will lead the VCU portion of a multi-site project in collaboration with the University of Pittsburgh studying a new compound that may target smokers who have not benefitted from existing therapies. Brunzell will direct pre-clinical studies for the $2 million, multiyear project that is funded by NIH’s National Center for Advancing Translational Sciences (NCATS) Drug Discovery Program.

“Nicotine in tobacco targets many different molecules in the brain that promote smoking behavior. Typically, people are satisfied for a period of time after smoking a cigarette. Our basic science studies demonstrate that this is due to stimulation of a molecular off-switch,” Brunzell said. “The Janssen compound we are testing will increase the likelihood that this off-switch is activated, and this should decrease the desire to smoke.” In forging partnerships between pharmaceutical companies and academic researchers, NCATS hopes to expedite the development of previously tested compounds for new uses. Positive results from Brunzell’s research will enable this novel therapeutic for smoking cessation to move on to early Phase II clinical trials within a year.

BEST PRACTICES FOR BATTLING HOSPITAL INFECTIONS Michael Edmond, M.D., professor of Internal Medicine Richard Wenzel, M.D., professor of Internal Medicine Hospitals must manage the constant threat that incoming patients might carry antibioticEDMOND resistant pathogens into its wards. How best to manage this risk is up for debate: Is it better to screen patients for the bugs and isolate carriers? Or to clean all patients as if they carry the bugs? A study published in the New England Journal of Medicine found that bathing patients with antiseptic soap upon admission WENZEL to intensive care units was more effective at preventing invasive infections with MRSA (methicillin-resistant Staphylococcus aureus) than was taking cultures and isolating MRSA carriers. Edmond and Wenzel wrote an accompanying editorial in the Journal, entitled “Screening Inpatients for MRSA — Case Closed,” calling for hospitals to take action based on the findings and stop screening patients. Not only does antiseptic treatment work better, but also it kills other pathogens and avoids the difficulties of isolating colonized patients, the researchers write. > Published in the June 13, 2013, issue of the New England Journal of Medicine

ELUSIVE STRUCTURE OF LIPID ENZYME REVEALED Sarah Spiegel, Ph.D., the Mann T. and Sara D. Lowry Professor in Oncology and chair of the Department of Biochemistry and Molecular Biology

SPIEGEL

Santiago Lima, Ph.D., postdoctoral fellow in the Department of Biochemistry and Molecular Biology

Sphingosine kinase 1 is an important enzyme because it produces sphingosine-1-phosphate, a lipid that functions as a signaling molecule in the cell and that plays a role in cancer progression, inflammation and cardiovascular disease. Now the enzyme’s LIMA structure has been described down to the atomic level by a research team at Amgen in San Francisco. Spiegel, who first described the signaling molecule sphingosine-1-phosphate in the 1990s, was invited to write a commentary of the new findings for the Cell Press journal Structure. “These findings will provide us with molecular tools to understand the functions of this important enzyme as well as development of new drugs that target it in cancer and inflammation,” she and her co-author Lima wrote. > Published in the May 8, 2013, issue of Structure

KAZAKHSTAN SCHOLARS STUDY HEALTHCARE POLICY Situated at the crossroads of Europe and Asia, bordering Russia, China and other Central Asian countries, U.S. ally Kazakhstan is credited with bringing a measure of stability to the region. In 1993, it launched the Bolashak scholarship program to develop and modernize society by sending scholars to study abroad.

The Department of Healthcare Policy and Research’s Askar Chukmaitov, M.D., Ph.D., is a Kazakh native.

His successful proposal to the Bolashak program has brought the first pair of scholars to campus to train, hosted by Chukmaitov’s home department and VCU’s Global Education Office.

Aygul K. Kaptagayeva, M.D., Ph.D., D.Sc., and Raushan Issayeva, M.D., D.Sc., are health care policy makers with years of experience in the areas of postgraduate medical education, medical sciences and human resource development in Kazakhstan. Through the internship program, they will study principles of health care policy, management and research so that

they can assist Kazakhstan’s government and Ministry of Health on their return.

“It is our hope that this internship is the first step toward a fruitful and long-lasting academic and research collaboration with scholars and the Bolashak program,” Chukmaitov said. Kaptagayeva is director of the Center of Education in Health at the National Center for Health Development, and Issayeva is deputy director of the Center for Life Sciences at Nazarbayev University.

IMPROVING RADIATION TREATMENT OF BRAIN CANCERS Kristoffer Valerie, Ph.D., co-leader of the Radiation Biology and Oncology research program and professor in the Department of Radiation Oncology One of the more grim cancer diagnoses is glioblastoma, which once diagnosed, usually kills patients in 12-15 months. Now, a novel drug has been shown to sensitize glioma cancer cells to the effects of radiation, thereby having the potential to improve therapeutic outcomes. Valerie used a mouse model of human glioblastoma multiforme and found increased survival times in the animals when the novel drug was combined with radiation treatment. The drug, which inhibits an enzyme called ATM kinase, appears to block cancer cells’ ability to repair DNA. Radiation damages DNA – the last thing radiation oncologists want is for the tumor cells to repair the damage and continue to grow. “If these findings hold up in early phase clinical trials, we expect patients with p53 mutant gliomas to respond well to this treatment while showing few side effects. Also, we anticipate that this same treatment strategy could be effective for other cancers that are treated with radiation and other DNA-damaging chemotherapies,” Valerie says. As encouraged as he is though, Valerie says more work is needed before they can proceed with human trials. > Published in the June 15, 2013, issue of Clinical Cancer Research

NOVEL IMMUNOTHERAPY WORKS LIKE VACCINE AGAINST CANCER SPREAD Xiang-Yang (Shawn) Wang, Ph.D., Harrison Endowed Scholar in Cancer Research, member of the Cancer Molecular Genetics research program at VCU Massey Cancer Center, VCU Institute of Molecular Medicine and professor of Human and Molecular Genetics One of the worst things about cancer is when tumor cells metastasize, moving to other parts of the body to start new cancerous growths. A research effort led

by Wang uses a highly engineered drug molecule that acts as a potent immune stimulator, triggering a systemic immune response that is able to seek out tumor cells and to quash them. The drug molecule is called Flagrp-170, which combines enhanced immune recognition of tumor cells with a bacterial danger signal to achieve highly effective antitumor vaccination. “This immunotherapy has the potential to be used alone or in combination with conventional cancer treatments to develop and establish immune protection against cancer and its metastases,” Wang says. “More experiments are needed, but we are hoping Flagrp-170 may one day be used in formulating more effective therapeutic cancer vaccines.” Wang wants to understand better the precise mechanisms involved so that he might optimize the strategy for the best anti-metastasis effect. > Published in the April 1, 2013, edition of Cancer Research

SEARCHING FOR MENTAL ILLNESS GENES Kenneth Kendler, M.D., the Rachel Brown Banks Distinguished Professor of Psychiatry and professor of human and molecular genetics The biological bases for psychiatric disorders are not well understood, but it’s been clear that genetics are involved to some degree. The search for genes that contribute or predispose people to autism, attention deficit-hyperactivity disorder, bipolar disorder, major depressive disorder and schizophrenia is hampered by numbers – how many patients with clear diagnoses have been screened for genetic markers. Recently

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an international team of researchers, co-directed by Kendler, compiled a huge database from a variety of sources to accomplish the largest genetic study of psychiatric illnesses to date, including more than 33,000 patients and nearly 30,000 control subjects.

The findings advance the understanding of psychiatric illness on the molecular level and could be used to develop potential target therapies directed at specific molecular pathways. > Published in the April 20, 2103, issue of The Lancet

NOVEL CHEMOTHERAPY DELIVERS A ONE-TWO PUNCH TO LEUKEMIA Steven Grant, M.D., Shirley Carter Olsson and Sture Gordon Olsson Chair in Oncology Research, associate director for translational research, program co-leader of Developmental Therapeutics and Cancer Cell Signaling research member at VCU Massey Cancer Center A one-two punch delivered by a novel drug combination shows promise in treating leukemia, according to a new study. Both drugs target cancer cell survival strategies, and combining them appears to shift the odds in the patient’s favor. One agent, called ABT-737, targets the cancer cell’s defense against programmed cell death (or apoptosis). The other drug, called BEZ235, interrupts a second pathway that would otherwise help the cancer cell escape apoptosis.

The drug combination may be particularly useful in patients with acute myelogenous leukemia. “This study builds on many years of work in our laboratory investigating the mechanisms regulating apoptosis in

human leukemia cells,” Grant says. “These findings could lead to a new therapeutic strategy for patients with AML and potentially other diseases by targeting patients whose leukemia cells display activation of a specific survival pathway known as AKT.” > Published in the Feb. 15, 2013 issue of Cancer Research

MOLECULAR DETAILS OF CELL’S RESPONSE TO STRESS Qinglian Liu, Ph.D., assistant professor in the Department of Physiology and Biophysics Heat shock proteins have key functions in cells, including the regulation of protein processing, folding and transport. They also play a crucial role in how cells respond to various kinds of stress. One well-studied heat shock protein, known as Hsp70, uses energy from ATP to do its jobs, but the molecular details of this interaction have only now been revealed. Liu and her colleagues at VCU, Columbia University and Brookhaven National Laboratory used X-ray crystallography to show the molecular structure – to the atomic level – of Hsp70 interacting with ATP. “Understanding the structural properties at the atomic level and molecular working of Hsp70s will pave the foundation for designing efficient and potent small molecule drugs to specifically modulate the function of Hsp70s,” Liu says. Hsp70 has been linked to cellular dysfunctions involved in cancer, aging and neurodegeneration. > Published in the July 201 3 issue of Nature Structural & Molecular Biology

HONORS& ACCOLADES Arun Sanyal, M.D., professor of Internal Medicine and holder of the Charles M. Caravati Distinguished Professorship in Gastroenterology, has received a pair of honors. He was elected an honorary member of the Hungarian Society of Gastroenterology and this summer received its Géza Hetényi Medallion Award. Earlier in the year, Sanyal was presented with the Ranbaxy Research Award in the field of Medical Sciences — Clinical Research by the Ranbaxy Science Foundation at a ceremony in New Delhi. Sanyal has an international reputation for his highly productive and well-funded work in non-alcoholic liver disease.

Louis De Felice, Ph.D., professor and vice chair in the Department of Physiology and Biophysics, was honored by the Biophysical Society with its Emily M. Gray Award. De Felice was selected for his enduring and multifaceted efforts to encourage the development and dissemination of knowledge in biophysics through outreach and education. As this year’s awardee, he presented the keynote Emily M. Gray Lecture at the annual meeting’s Student Symposium.

De Felice, who also serves as assistant dean of graduate education in the School of Medicine, is known as an advocate for students who come from disadvantaged or non-traditional backgrounds.

Kurt F. Hauser, Ph.D., the Wazeter Professor in the Department of Pharmacology and Toxicology, accepted the Wybran Award from the Society on NeuroImmune Pharmacology at its 19th Scientific Conference. The Wybran Award is the highest honor bestowed

by SNIP in recognition of the very best scientific contributions that have resulted in the preservation and expansion of the field of neuroimmune pharmacology. The award is named for Joe Wybran, a renowned scientist whose work integrated the fields of neuroimmunology, drugs of abuse and immunity to infection. After his death in 1989, the award was created to memorialize his scientific contributions that underpin SNIP.

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Virginia Innovation Partnership Funds Early-Stage Research Projects A STATEWIDE NETWORK, known as the Virginia Innovation Partnership, has chosen five VCU projects for proof-ofconcept funding to advance early-stage research. Totaling $258,000, VCU’s five funded proposals represented the highest dollar award total of any Virginia university.

Designed to accelerate innovation and economic growth, VIP also connects academic researchers with mentors, corporations and investors to accelerate commercialization of the new discoveries.

Those mentoring teams include VCU Tech Transfer staff and advisors, who helped prepare the proposals of the winning teams.

Three of the five projects come out of the medical school: :: The Department of Microbiology and Immunology’s Jason Carlyon, Ph.D., associate professor, and Richard Marconi, Ph.D., professor, are developing a novel chimeric vaccine to protect against Lyme disease and granulocytic anaplasmosis, another tick-borne illness that can be co-transmitted with Lyme disease. :: Lynne Gehr, M.D., assistant professor of anesthesiology, and Todd Gehr, M.D., professor of internal medicine, are creating a device that detects an early biomarker of ischemia so physicians can rapidly intervene in the case of heart attack. :: The Department of Internal Medicine’s Aamer Syed, M.D., assistant professor, and Hans Lee, M.D., now at Johns Hopkins University, are designing a flexible bronchoscope to more easily place stents that open the airways of patients with lung disease, tumors or scar tissue.

Dean’s Discovery Initiative Volume 12, Number 2 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.

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 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 and Jennifer C. Uscher Photographers: Allen Jones, Thomas Kojcsich, Kevin Schindler, and VCU Creative Services Graphic Design: Zeigler/Dacus © Virginia Commonwealth University, 2013.

$62 million study of traumatic brain injuries is largest ever awarded to VCU In August, the White House announced VCU will oversee a national research consortium of universities, hospitals and clinics to study what happens to service members and veterans who suffer mild traumatic brain injuries or concussion.

David X. Cifu, M.D., serves as principal investigator on the $62 million award from the Departments of Defense and Veterans Affairs.

The study will include concussions from both combat injuries, such as those from blasts and bullets, and civilian injuries, such as those from car accidents, sports injuries and falls.

“The research across the rehabilitation medicine spectrum, particularly as it relates to traumatic brain injuries and military personnel, was the springboard to this research grant,” said Sheldon Retchin, M.D., senior vice president of VCU Health Sciences and CEO of the VCU Health System.

DAVID X. CIFU, M.D., IS CHAIR AND THE HERMAN J. FLAX PROFESSOR IN THE DEPARTMENT OF PHYSICAL MEDICINE AND REHABILITATION AND ALSO SERVES AS NATIONAL DIRECTOR OF THE PM&R PROGRAM OFFICE WITHIN THE VETERANS HEALTH ADMINISTRATION.

MCV Foundation School of Medicine

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