A Medical Mission
(This is part 1 of 6 of a series of articles excerpted from "A Medical Mission" in the Spring/Summer 2009 issue of Georgetown Magazine)
Unbounded Potential.
This is what Howard Federoff, MD, PhD, the new executive vice president for health sciences and executive dean of the School of Medicine, cited as a primary reason he accepted the job at the Georgetown University Medical Center in 2007.
“There is great potential for Georgetown to be a leader in biomedical sciences, not just locally, but nationally and internationally, and there is a remarkably fertile foundation to build upon here,” said Federoff, who came to Georgetown from the University of Rochester School of Medicine, where he served in positions that included senior associate dean for basic research. “Investigators at GUMC have made truly outstanding contributions that have helped to shape the manner in which medicine is taught and clinical care is delivered.”
The largest Catholic medical center in the United States is now a $225 million operation and home to more than 77 percent of Georgetown’s annual sponsored research expenditures, bringing in more than $132 million in external funds during fiscal year 2008.
Since Federoff joined Georgetown in April 2007, GUMC researchers have received multimillion dollar federal awards to study many serious diseases and conditions, including breast cancer, Alzheimer’s disease, childhood cancers, traumatic brain injury, Parkinson’s disease, GI cancers and brain development in children.
And applications are on the rise for the School of Medicine. In 2007, there were 10,643 applications for 190 slots. For the 2008 incoming class, 11,237 applications competed for 194 slots. And for the 2009 incoming class, applications are already exceeding last year’s.
The new leadership of GUMC, including Louis Weiner, MD, whom Federoff hired as the director of GUMC’s Lombardi Comprehensive Cancer Center last year, isn’t resting on its proverbial laurels. They want GUMC to grow, and Federoff believes that includes more partnerships and collaborations with outside institutions, building on current research strengths, and having a multidimensional approach to health that takes into account both genetic and environmental risk factors to prevent disease before it starts.
“When I met Howard Federoff and heard his vision for academic medicine, I knew he was the right choice for Georgetown,” President John J. DeGioia, PhD, recalls.
One important GUMC collaboration announced this past October is a Comprehensive Research and Development Agreement with the Oak Ridge National Laboratory (ORNL). Located in Tennessee, ORNL is the United States Department of Energy’s largest science and energy laboratory. The collaboration will help GUMC analyze, manage and visualize complex molecular data collected at the university, facilitating additional biomedical research in the areas of structural biology, systems genetics, biomarkers, computational biology and radiation biology, among others. Oak Ridge wants to work with Georgetown scientists to present research proposals to NIH and other entities.
“We are extremely pleased to be strengthening our collaborative research relationship with Oak Ridge National Laboratories,” Federoff says. “This collaboration brings us one step closer to being able to employ a (preventative) approach to health and medicine and improve human health.”
To date, there are three research projects involving ORNL and GUMC.
GUMC’s Steve Byers, PhD, a professor of oncology, is working with ORNL’s Gary Van Berkel, developing ways to enhance the measurement of biomolecules and to increase understanding of how drugs and their metabolites work on tumors. Zofia Zukowska, MD, PhD, chair of the department of physiology and biophysics, is working with ORNL colleague Brynn Voy to further define the interface between genetic susceptibility to stress and obesity. Minetta Liu, PhD, associate professor of medicine and oncology, is working with ORNL’s Ram Datar, utilizing a membrane developed by ORNL to help further her work to detect the earliest metastatic spread of cancer cells.
Future Possibilities
Part of Federoff’s vision is that one day, new parents will receive a summary of diseases to which their baby will be susceptible and a report telling them how to prevent or control such such disorders.
These advances, he says, may be a result of the decoding of the human genome, which took place between 1986 and 2003.
“Medicine will be most effective when the focus of health care changes from treatment of the symptoms of disease to holistic prevention of it,” Federoff says. “Instead of being reactive – waiting for sick patients to walk through the clinic door – physicians will be proactive, advising and treating the healthy so that they stay that way.”
One of the projects that best illustrates this preventative approach strives to understand why so-called triple negative breast cancer occurs much more frequently in African-American women than in other ethnic groups. The project, launched by Weiner with the support of Federoff, will then determine ways to intervene and reduce or eliminate that risk. This kind of cancer is so named because it does not display any of the cell surface receptors for estrogen, progesterone or for the growth factors HER2 that provide targets for treatment. Triple negative cancers also seem to be more aggressive than other forms of cancer.
“This is a huge health care problem for minority women everywhere, but especially in the District of Columbia, which has the highest breast cancer death rate in the United States,” Weiner says.
Cancer, no matter where it is located, is a disease for which a remarkable accumulation of genetic and biochemical knowledge in the last several decades hasn’t yet substantially transformed clinical practice, he explains.
“As physicians, we still practice 19th-century medicine because we are limited in what we can truly tell patients and prescribe for them,” Weiner says. “That means that a cancer patient who visits 10 different oncologists might receive 10 different recommendations for treatment.”
With a more systematic approach, doctors would have access to how the constellation of clinical, molecular, behavioral, epidemiologic and environmental factors conspires to create the particular cancer and the ways in which treatment is most likely to work.
The best way to understand triple negative cancer, for example, is to collect as much information as possible on each patient with the disease, which includes genetic information from individuals with this cancer.
That’s not unusual – but most molecular studies conducted today try to match just a few genes with cancer development and outcome. Weiner’s approach is to look at the whole genomic spectrum of individual patients, collecting data on activity levels of all of the 30,000 – 40,000 genes in each patient’s cancer cell.
Weiner also plans to rapidly invest in bioinformatics, which already is helping researchers collect and analyze the large volume of information in Lombardi’s database of cancer, known as G-DOC. The database takes information from patients in clinical trials and matches it up with the unique molecular characteristics of their cancers. This helps define the molecular features that both underlie the patient’s prognosis and predict the patient’s responsiveness to therapy, as well as serve as a guide to which therapy might work best. This information also can be used for target discovery and drug development.
“We’ve estimated that every patient will generate roughly 1,039 bytes of information, which is a number that’s so big it makes your head hurt,” Weiner says. Data on each patient will then be integrated into a data repository for all patients with the same cancer, along with how patients fared with treatment.
Federoff says the Medical Center is poised to make significant progress.
“We are on the verge of great change and growth, guided by cura personalis (care of the whole person),” he says. “The central problem in biomedicine will be to understand how to define the risk for major diseases and the role environment plays as a contributory influence on our inherited vulnerabilities. Our new partnerships, our research teams and our evolving curriculum are likely to make this a reality in the future.”
By Frank Reider, excerpted from the Spring/Summer 2009 issue of Georgetown Magazine
