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Week of 26 April 2002 · Vol. V, No. 32
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BU's Science and Technology Day on March 26 presented nearly 130 outstanding research posters by graduate students from both the Charles River and the Medical Campuses. Only 10 posters could be singled out for awards, but the judges remarked on the extraordinarily high quality of all the research, as well as the enormous diversity and range of disciplines represented. "Research Briefs" is highlighting this graduate research. For a list of awards, and access to abstracts of the work presented, visit http://www.bu.edu/research/ScienceDay/sciday2002.html.

Heavy lifting. Roger Fielding, an associate professor of health sciences at Sargent College, is a pioneer in establishing that weight training, even in the frail elderly, can rebuild muscle mass, strength, and power. Now one of Fielding's students, Nathan LeBrasseur (SAR'95,'97,'02), a doctoral candidate in applied anatomy and physiology, has conducted a novel in vivo study examining the cellular processes that lie behind the benefits of resistance training.

When muscles contract against a heavy load, proteins that result in the growth of individual muscle cells are synthesized, thereby enhancing the strength, size, and metabolic activity of muscle fibers. LeBrasseur studied a complex family of molecules called neuregulins (NRGs), known to activate growth in a number of cell types found in the skin, nerves, and heart muscle. His experiments demonstrate that when rat skeletal muscle is forced to contract, NRGs are activated, binding to receptors, known as ErbBs, on the muscle cells, and stimulating cell growth.

This may be the first step in developing novel therapeutic strategies to counteract the muscle deterioration that can accompany aging and diseases such as cancer, congestive heart failure, and AIDS.

LeBrasseur's work on the role of NRG/ErbB signaling network in muscle growth earned him the Sargent College Dean's Award at Science and Technology Day as well as a Professional Opportunity Award from the American Physiological Society. He recently presented his work at the 2002 Experimental Biology Meeting in New Orleans, La.

Putting on the brakes. Named Molecule of the Year by the journal Science in 1993, the protein known as p53, and its associated gene, plays a vital role in the suppression of tumors. P53 literally puts on the brakes, stopping cell division when it senses that a cell's DNA is damaged and the cell is likely to reproduce in the uncontrolled manner that leads to cancerous tumors. A defect in the p53 gene has been implicated in an estimated 60 percent of human cancers, including those of the breast, lungs, liver, skin, prostate, bladder, cervix, and colon. Although much has been learned about how p53 functions -- and malfunctions -- the mechanisms that lead to its activation remain largely unclear.

In an investigation that earned him the School of Medicine Dean's Award at Science and Technology Day, Hongwu Zheng (MED'02), a doctoral candidate working with MED Assistant Biochemistry Professor Zhi-Xiong Jim Xiao, is beginning to put that piece of the puzzle together.

Zheng's work reveals that when DNA is damaged, an interaction is initiated between p53 and Pin1, one of a group of enzymes present in the body that initiates the rearrangement of protein conformation. He further found that the interaction occurs at very specific binding sites on the protein, known as Ser33, Ser315, and Thr81. In cells lacking Pin1, the response of p53 upon DNA damage is defective, and the gene may not be fully activated, allowing the damaged cell to proliferate out of control.

Understanding this mechanism may lead to the development of therapeutic drugs that can intervene in the process, according to Zheng, and enhance the ability of p53 to stop a malignant cell that is out of control.

Zheng and Xiao collaborated in this work with Kun Ping Lu and his colleagues at Harvard Medical School and Takafumi Uchida at Tohoku University in Japan.

"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.

       

26 April 2002
Boston University
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