Bridge to the future

Clockwise from lower left: Christopher Newton-Cheh, Eric Morrow, Benjamin Ebert and James Bradner.
Clockwise from lower left: Christopher Newton-Cheh, Eric Morrow, Benjamin Ebert and James Bradner
Photo by Maria Nemchuk, Broad Institute

For academic scientists, the move from postdoctoral work to an independent research position is a major career step. But it can be especially taxing for physician-scientists, who juggle both clinical and laboratory duties. In a newly launched program designed to facilitate this transition, the Burroughs Wellcome Fund (BWF) recently awarded 20 career development grants to physician-scientists across the United States. Remarkably, four awardees — nearly a quarter of the recipients — are based in the Boston area, pursuing collaborative projects at the Broad Institute.

The new funding program, called the Career Awards for Medical Scientists (CAMS), was established by the BWF in May 2006 to boost the number of physician-scientists pursuing research careers. Patterned after the foundation’s successful program for the basic biomedical sciences, the first class of CAMS awardees were announced last month.

The inaugural recipients of the CAMS awards were chosen from a pool of more than 150 applicants and will receive $700,000 in “bridging” funds, which will be disbursed over a five-year period spanning the transition from postdoctoral fellow to junior faculty. Among the awardees are researchers James Bradner, Benjamin Ebert, Eric Morrow, and Christopher Newton-Cheh.

James Bradner, a hematologist/oncologist at the Dana-Farber Cancer Institute and a postdoctoral fellow in the Broad’s Chemical Biology program, will apply the BWF award to continue his studies of a family of proteins called histone deacteylases, or HDACs. These proteins fill diverse roles in cells, from controlling gene activity to shuttling key cellular cargo. Using a combination of chemical and high-throughput methods, Bradner engineered a series of small molecular inhibitors that selectively interfere with the activity of individual HDAC family members. He will now use these HDAC inhibitors to study important aspects of cancer biology. In particular, he hopes to uncover ways to thwart the cellular signals leading to multiple myeloma, a form of blood cancer, and to block cancer cell migration, a critical step in the spread or “metastasis” of tumors.

Benjamin Ebert, a hematologist/oncologist at the Dana-Farber Cancer Institute and a postdoctoral fellow in the Broad’s Cancer program, focuses on understanding how blood cells mature, or differentiate. He is using genome-scale tools to uncover the genes that underlie a disorder of blood cell differentiation called myelodsyplasia (MDS). A kind of “pre-leukemia”, MDS affects more than 10,000 individuals in the United States each year, though virtually nothing is known about its molecular origins. With the BWF career award, Ebert will also explore ways to jump-start the early stages of blood cell differentiation that are blocked in MDS. Using similar technologies, he is also working on the identification of small molecules that reactivate the fetal form of the oxygen-ferrying protein hemoglobin. This approach holds promise for the treatment of sickle cell anemia and thalassemia, two common blood cell diseases.

Eric Morrow is a psychiatrist at Massachusetts General Hospital, an instructor in psychiatry at Harvard Medical School and a postdoctoral fellow in the Broad’s Program in Medical and Population Genetics. His research is aimed at unraveling the molecular basis of severe childhood neuropsychiatric disorders, particularly autism. Using a variety of gene-finding methods, Morrow is scouring the human genome to uncover the genetic underpinnings of autism. Some of this work relies on clusters of families in the Middle East that have a high incidence of autism; analyzing DNA from these families enables scientists to more readily map the culprit genes. Once suspects are identified, Morrow plans to pursue functional studies to determine the genes’ roles in neurodevelopment and disease.

Christopher Newton-Cheh is an attending cardiologist at Massachusetts General Hospital, an investigator with the Framingham Heart Study and a postdoctoral fellow in the Broad’s Program in Medical and Population Genetics. His work focuses on identifying the genetic factors that contribute to sudden cardiac arrest (SCA), a condition that arises when the heart suddenly stops beating, often without warning. Perturbations in the heart’s electrical activity increase the risk of SCA and can be readily detected via a routine clinical measurement called the QT interval. Newton-Cheh seeks to uncover the genetic differences that affect the QT interval using a variety of genomic methods, including whole-genome scanning and admixture mapping. Once identified, such differences may provide a practical handle for doctors to determine which patients are at risk of SCA — a condition that often goes undiagnosed until it is too late.