Contents
Critical Resources
An Eye to the Future: Training the Next Generation of Researchers
BASIC DISCOVERY TO TRANSLATIONAL RESEARCH
Edgar Charles treated patients infected with the hepatitis C virus during his residency in internal medicine and fellowship in infectious diseases at New York University School of Medicine. This viral infection is one of the most common causes of chronic liver disease and organ transplantation in the United States. One of the many puzzling aspects of the disease is that some patients also develop an inflammation of the blood vessels, probably due to the presence in the blood of certain types of immunoglobulin. These molecules are normally produced by the plasma cells of the immune system to identify and neutralize foreign substances, such as bacteria and viruses, and in some diseases, they also can attack normal cells and tissues in the body. Additionally, some patients with hepatitis C infection suffer from a type of immune system cancer called non-Hodgkin's lymphoma.
Charles reasoned that more research was needed to fully understand the disease and, in particular, the role B cells of the immune system were playing in it. Although the two-year fellowship he had undertaken at New York University included a year of research, Charles said that "to do more research seriously, I would have to have more training." He was not, however, sure of how to go about getting that training.
After considering different training programs, he learned about the Clinical Scholars Program offered by The Rockefeller University's Center for Clinical and Translational Science — a member of the CTSA consortium. This three-year program, which leads to a master's degree in clinical and translational research, gives a junior investigator, typically a physician, the opportunity to join the laboratories of established scientists who provide mentorship for the scholar's research. The mentored research project is complemented by a curriculum that provides education in several core competencies, including the responsible conduct of research, biostatistics and standards for conducting clinical studies. "Once I looked into the program, it was a very clear choice for me to do it," Charles said.
In his early efforts, he arranged to conduct a research project to study B-cell function in patients with hepatitis C infection under the joint supervision of Charles Rice, a renowned virologist, and Lynn Dustin, a distinguished immunologist, at The Rockefeller University. Charles first had to obtain blood samples from patients. For this aspect of the study, the assistance he received from the Center for Clinical and Translational Science was invaluable. The Center's staff helped Charles obtain approval for his proposal from his institutional review board (IRB) — typically a daunting undertaking — such that he was able to quickly start his research. (An institution's IRB considers ethical, policy and regulatory issues regarding patient research.) Nurses and other medical staff then helped Charles recruit suitable patients and collect samples.
In Dustin's laboratory, Charles began learning how to operate as a scientist. "Edgar was beautifully trained clinically, and he had done some bench work before, but when he first came to my lab, he was not yet able to function independently as a scientist," Dustin said. "I started out suggesting experiments for him and teaching him procedures. I also critiqued his writing for grant applications and papers." In the laboratory, Charles learned to carry out different sophisticated molecular and biochemical analyses on the B cells he isolated from patients' blood.
Through his research, Charles discovered that the hepatitis C virus causes certain B cells that produce a particular type of immunoglobulin to greatly increase in numbers. He published his findings in the prestigious scientific journal Blood in February 2008. Based on this work and a grant proposal he wrote describing future studies, Charles received a Mentored Clinical Scientist Development Award from NIH's National Institute of Allergy and Infectious Diseases. The award provides support for up to five years to help recipients transition from mentored research to an independent research position. "Developing the skills to become an independent clinical investigator is precisely the goal we set for trainees in our master's program, and so we are delighted with Dr. Charles' success," said Barry Coller, director of the Center for Clinical and Translational Science.
Charles started with a medical problem and used basic laboratory science to find possible answers for it. His findings are providing insights into what causes the disease symptoms associated with hepatitis C infection and may someday offer clues on developing treatments to alleviate such symptoms. The next step in the continuum of translational and clinical research is the translation of laboratory findings to patients — a step that requires its own set of competencies, as well as a dedicated infrastructure for clinical studies.
