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On a mission. As his mother waited for a kidney match, James Chen (MED'01,'03), then only five years old, decided that someday he would learn what causes the body's cells to malfunction, and use that information to help people. Now a Dean's Fellow and a Ph.D. and M.D. student in the laboratory of MED Cancer Research Center Director Douglas Faller, Chen earned the President's Award at Science Day recently for his investigation of how a class of drugs called short chain fatty acids (SCFA) affects the cell cycle. This basic science may hold the key to a new, more effective category of anticancer agents.

Chen's research focuses on butyrate, a drug typically used to treat sickle cell anemia. In this disease, the enzymes in red blood cells that carry oxygen, known as globins, do not function correctly. Butyrate activates a fetal form of hemoglobin to replace malfunctioning adult hemoglobin, but it also slows the rate at which red blood cells mature. Although the effect on growth is less ideal for the treatment of sickle cell anemia, it might make butyrate useful in slowing the proliferation of cancer cells.

Further investigation revealed that butyrate reversibly stalls the cell cycle in normal cells, but in some models of cancer it goes further and kills tumor cells. This is a valuable feature for cancer therapy, since normal cells return to full function once the drug is gone from the body.

The protein produced by gene p21 was already known to stop cells from cycling. The Faller lab established that it was not the only protein involved since butyrate effectively stopped the cell cycle in mice bred without gene p21. Chen's research established that butyrate elevates the level of p27 in cells and that p27 is essential to the process of stalling the cell cycle in normal cells.

Chen believes that by better understanding the mechanisms by which drugs such as butyrate regulate the cell cycle, scientists will be able to rationally design more effective drugs. It is clear from this research, he says, that a derivative of butyrate that does not increase p27 levels will be better for diseases like sickle cell anemia. Those that increase levels of p27 may prove more effective for cancer therapies.


Physician, heal thyself. A root canal can be a painful experience, and not only for the patient. Karen Jacobs, a clinical associate professor of occupational therapy at Sargent College, notes that dental professionals are increasingly affected by work-related musculoskeletal disorders (WRMDs), the aches and pains that come from repetitive, precision tasks requiring long periods of relative stillness and the manipulation of small tools in a limited space.

Dentists and dental hygienists are exposed to a variety of factors that stress their bones and muscles, including repetition, force, awkward and static posture, vibration, mechanical stresses, and cold. The result: WRMDs in this group account for 34 percent of all injuries and illnesses resulting in lost workdays, with 63 to 93 percent of dental hygienists and 42 to 72 percent of dentists reporting low back, neck, shoulder, arm, or hand pain.

Jacobs has a plan to help relieve the pain. With support from a recent grant from the Small Business Administration's Innovation Research Program and in partnership with New England Research Institutes, Inc., of Watertown, Mass., she is developing an interactive Web site to assist dental professionals in coping with the ergonomic stresses of their profession. The proposed site will train dental professionals to recognize, avoid, and prevent potential hazards, and instruct workers and employers about the new Occupational Safety and Health Administration draft program standards on ergonomics. Dental professionals will earn continuing education credits for online participation in the program.

"Research Briefs" is written by Joan Schwartz in the Office of the Provost. To read more about BU research, visit http://www.bu.edu/research.

       

15 May 2003
Boston University
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