Bridging the "Great Divide" in Biomedical Research

Biomedical research is split into two main tracks: basic (bench) science and clinical research. But this "great divide" is not impossible to bridge, and that bridging of disciplines is often called "translational research." Einstein has led the way by training translational scientists and encouraging interconnection and cross-pollination among physicians and bench scientists whenever possible.

As part of this ongoing effort, Einstein-Montefiore's eCLIPSE (Education Connecting Laboratory Investigation and Population Science) program "seeks to cross the methodological divide," said Dr. Paul Marantz, associate dean for clinical research education.

Dr. Marantz is one of three co-directors of eCLIPSE. The other co-directors are Dr. Louis Weiss, professor of pathology and of medicine, and Dr. Ellie Schoenbaum, professor of epidemiology & population health and director of the Clinical Research Training Program (CRTP), a two-year master's degree program Einstein founded in 1998 to train doctors in the clinical/population sciences.

The five-year eCLIPSE program is an interdisciplinary Ph.D. in clinical investigation available to students enrolled in Einstein's graduate division, and to M.D.-Ph.D. students in Einstein's Medical Scientist Training Program.

CRTP and eCLIPSE provide "a mentored research experience," said Dr. Marantz, and the programs share a core curriculum of epidemiology, clinical research methodology and biostatistics/data analysis.

eCLIPSE was launched with a Clinical and Translational Science Award in 2006from the National Institutes of Health's National Center for Advancing Translational Sciences. In 2012, Einstein also received an Institutional Program Unifying Population and Laboratory-Based Sciences (PUP) award from the Burroughs Wellcome Fund. Given to just 10 institutions since its inception in 2008, the PUP award provides $500,000 a year to five-year programs such as eCLIPSE that "bridge the gap between the population and computational sciences and the laboratory-based biological sciences."

Program Pioneers

eCLIPSE scholar Catherine Manix Feintuch (left), Ryung Kim, Ph.D. (middle), Johanna Daily M.D.Ten students currently are in various stages of completing the eCLIPSE program. One of them is Catherine Manix Feintuch—the prototypical student that Drs. Marantz and Weiss had in mind when they wrote the grant proposal for eCLIPSE. She was among the first students to enroll, and plans to defend her thesis in June.

"Before I was a Ph.D. student, I completed the Certificate of Public Health through Einstein's Center for Public Health Sciences and joined the eCLIPSE program as a more advanced student, because I had already completed my epidemiology and statistics coursework," said Ms. Feintuch.

Ms. Feintuch's mentors are statistician Dr. Ryung Kim, assistant professor of epidemiology & population health, and health internist and global health researcher Dr. Johanna Daily, who is associate professor of medicine. Since 2009, they have collaborated on field-based epidemiological and biostatistical analyses of children with malaria. Their work has been published in Infection and Immunity, the Journal of Infectious Diseases and PLOS ONE, and has yielded seven grant proposals.

Ms. Feintuch is doing her thesis research on immune and genetic factors associated with the progression and severity of cerebral malaria—the deadliest form of the disease—in Dr. Daily's lab. This has included two trips to Africa, where she learned how to conduct field research from physicians and scientists who collaborate on the Blantyre Malaria Project at Queen Elizabeth Hospital in Blantyre, Malawi.

"Catherine joined my lab because she wanted to develop the epidemiology and biostatistical skills necessary to conduct prospective translational research involving human subjects," said Dr. Daily.

"Unlike mice, which are clonal, human beings are diverse on so many levels, and you don't want to draw the wrong conclusions when you are analyzing data from a human cohort," Dr. Daily added. "eCLIPSE trains students to design robust studies that enroll subjects who are representative of all the patients who have a particular disease, and also take into consideration any variables that may affect the outcome. A well-designed and analyzed study can overcome the diversity in human genes and epidemiological factors to identify disease mechanisms, and I wanted Catherine to develop skills to do this well."

"If I stayed in New York, I would have processed samples. But in Malawi, I got to see patients and learned about their clinical care and course of disease," said Ms. Feintuch, adding, "Seeing the clinical side generated questions and hypotheses I never would have thought of just looking at a spreadsheet of clinical data."

Dr. Kim had been informally mentoring Catherine in statistics for several years, but when she enrolled in eCLIPSE, she asked him to become her program co-mentor. In addition to her thesis, she is working with Dr. Kim on a population science paper, "Determinants of International Donor Assistance for Global Malaria Control." The aim of their study is to assess the relative importance of factors such as years lost to disability or premature death, past success of a recipient in administering an aid program, and donor self-interest (for instance, trade and commerce) in determining malaria aid.

"Understanding how aid is allocated can help improve aid effectiveness, and I don't think Catherine would have had a chance to study this if she had not been in the program," said Dr. Kim.

Student with a Mission

eCLIPSE scholar Wouter Hoogenboom (left), Michael Lipton, M.D., Ph.D. (middle), Craig Branch, Ph.D.Armed with a master's degree in neuropsychology from Maastricht University in the Netherlands, first-year student Wouter Hoogenboom enrolled as a predoctoral student because, he said, "the eCLIPSE program will help me develop the unique skills and project experience needed to be successful as an independent investigator who can start and fund my own research projects."

Mr. Hoogenboom's eCLIPSE mentors are neuroradiologist/neuroscientists Drs. Michael Lipton and Craig Branch.

"Students in the program usually spend each trimester of the first year rotating among three labs before choosing one for their thesis research, but Wouter came here knowing he wanted to work with me," said Dr. Lipton, professor of radiology, of psychiatry and behavioral sciences and in the Dominick P. Purpura Department of Neuroscience, as well as associate director of the Gruss Magnetic Resonance Research Center (MRRC).

"Before I joined Einstein, I worked in a psychiatry neuroimaging laboratory in Boston that was collaborating with Dr. Lipton on a research project involving head injuries, so I was familiar with his work," Mr. Hoogenboom explained.

"I am not here just to answer questions," said Dr. Lipton. "We mentors are actively engaged, and meet on a regular basis, discuss where he is in a project, assess and critique and set goals for the next meeting."

It was Dr. Lipton who suggested that Mr. Hoogenboom tap Dr. Branch, associate professor of radiology and of physiology & biophysics, MRRC director and co-director of the EGLCF Integrated Imaging Program, as his second mentor. The two have since collaborated on defining the pathophysiological mechanisms underlying subtle white-matter injury with the aid of diffusion tensor imaging (DTI)—a form of magnetic resonance imaging—as part of a larger study on soccer-related mild traumatic brain injury (mTBI).

"Dr. Lipton is involved in human research, and suggested I look into animal models. So I did a rotation in Dr. Branch's lab to get experience with rodents, which I didn't previously have," said Mr. Hoogenboom.

Reproducing the human DTI findings in a rodent model of mTBI that Dr. Branch developed, Mr. Hoogenboom's research will examine such brain injuries from a mechanistic level, to aid in "understanding how brain pathology evolves following an mTBI. The goal is to facilitate individualized prognosis and identify targets for therapy," explained Dr. Lipton.

"Because this research is truly translational in nature, Wouter will gain an understanding of both the basic and clinical efforts, and how to intertwine them in a productive manner," added Dr. Branch.

This project, which involves "neuroimaging tools to study the brain in a sports-related and translational research setting, fits my interests perfectly," said Mr. Hoogenboom.