C. elegans expressing the AMPK protein in green.

C. elegans expressing the AMPK protein in green.

TREC center at HSPH tackles obesity, cancer prevention

May 11, 2012

Research has linked obesity with the development and progression of many health problems including multiple forms of cancer. But questions remain about the complex mechanisms by which obesity develops and how it affects cancer risk and survivorship. Now, Harvard School of Public Health (HSPH) researchers are collaborating with colleagues from institutions across the country to explore those questions from multiple angles, from the molecular to the societal level, through an initiative called Transdisciplinary Research on Energetics and Cancer (TREC).

HSPH was awarded a five-year grant last June from the National Cancer Institute to form one of four new research centers sponsored by the TREC initiative. Led by Frank Hu, professor of nutrition and epidemiology and co-director of HSPH’s Program on Obesity Epidemiology and Prevention, researchers involved with the Harvard TREC Center hope to translate their findings into strategies for improving the public’s health.

Dietary restriction

The Center recently awarded funding to several pilot projects, including one led by William Mair, assistant professor of genetics and complex diseases, that explores the link between caloric intake and cancer and other aging-related diseases. Research in multiple species including non-human primates has shown that dietary restriction—reducing caloric intake by 30% but not to the point of malnutrition—prolongs life and reduces cancer risk. Mair explains that this phenomenon is an evolutionary adaptive strategy. Certain cell functions in animals shut down in response to nutritional stress, he said, while others are up-regulated to provide protection against disease. But there are detrimental side effects to drastically lowering caloric intake, Mair said, and he would never recommend that people try dietary restriction on their own.

Mair’s lab is working to tease out the genetic pathways that are responsible for the positive health effects of dietary restriction. His work centers on activation of a protein called AMPK, which Mair describes as a “cellular fuel gauge.” AMPK becomes activated when energy is low. It shuts down processes that consume a cell’s energy and turns on those that replenish the cells. Mair has demonstrated in experiments using the nematode worm C. elegans—which has a lifespan of two weeks and allows for easy genetic manipulation—that activating AMPK mimics the protective effects of a restricted diet. Further research on the cellular mechanics of these creatures, which go through a visible aging process during their brief lifetime, can then be applied to the study of more complex mouse models, and ultimately may lead to new drug targets.

“TREC is exciting to me as someone new to the School,” Mair said. “I hope that it will get people who are working on different parts of the same question into the same room and open up new avenues for collaboration.”

The built environment

Another recently funded project, led by HSPH’s Francine Laden, Mark and Catherine Winkler associate professor of environmental epidemiology, will explore the effects of the built environment on health behavior. Laden studies how factors of urban design, such as connectivity of streets, mix of residential and commercial buildings, and perceived neighborhood safety influence people’s physical activity. Laden presented her work at the center’s first annual conference, held on February 13, 2012.

The conference drew a crowd of TREC investigators from HSPH and other institutions, in addition to students and young scientists. Keynote speaker Nathan Berger, Hanna-Payne professor of experimental medicine and director of the Center for Science, Health and Society at Case Western Reserve University, likened the TREC initiative to other major collaborative scientific undertakings such as the global fight against HIV/AIDS. Berger directed Case Western’s TREC Center.

The Harvard TREC Center draws on the multidisciplinary expertise of the faculty of HSPH, Harvard Medical School, Brigham and Women’s Hospital, Children’s Hospital Boston, Dana-Farber/Harvard Cancer Center, Harvard Pilgrim Health Care Institute, and the Harvard Center for Population Studies.

–Amy Roeder

Photo courtesy of William Mair