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Bruce M. Spiegelman, Ph.D.

Contact

Bruce_Spiegelman @ dfci.harvard.edu

Website

http://research2.dfci.harvard.edu/spiegelmanlab

Biography

Born: November 14, 1952 in Bay Shore, New York Education: (BS) -- College of William and Mary, Williamsburg, VA, 1974, Ph.D. -- Princeton University, Princeton, NJ, 1978, Postdoctoral Fellowship -- Massachusetts Institute of Technology, Cambridge, MA, 1979-1982 Positions and affiliations: Professor of Cell Biology and Department of Cancer Biology, Dana-Farber Cancer Institute and Harvard Medical School since 1993. Awards and Honors: Elected, National Academy of Sciences 2002, Elected Foreign Associate, European Molecular Biology Organization 2006, Weiland Prize from the University of Munich 1997, Rolf Luft Award in Endocrinology from the Karolinska Institute 2003, Bristol-Myers Squibb Award for Distinguished Achievement in Metabolic Research 2003

Research Summary

We are interested in the basic bioenergetics of the heart in healthy and heart failure. Specifically, we are studying how PGC-1a and PGC-1b have an impact on cardiac metabolism. How does lack of PGC-1a lead to heart failure? Can elevations of PGC-1a suppress oxidative damage, ischemia/reperfusion injury and heart failure? We are using a combination of transgenic approaches and viral vectors to explore these issues. We collaborate on these questions with Drs. Tony Rosenzweig and Nils-Goran Larsson.

Preliminary findings: Ischemia/reperfusion of the rat heart after delivery of PGC-1a. Rats hearts were injected with adenovirus encoding for PGC-1a. 2 days later, the coronary artery was transiently ligated for 30 minutes, during which time fluorescent microspheres were injected systemically. 24 hours later, hearts were harvested, stained with TTC, and imaged. A: Sample transverse slice of a heart. Left panel shows microsphere fluorescence; non-labeled regions represent areas not perfused during ligation period. Right panel shows TTC staining of the same heart slice; TTC stains live tissue red. B: 2 and 3 rats were injected with adenovirus encoding for GFP and PGC-1a, respectively. The bar graph indicates the fraction of the area at risk (AAR, as determined by microsphere fluorescence) that developed myocardial infarction (as determined by TTC staining).

Publications

1. Arany Z, He H, Lin J, Hoyer K, Handschin C, Toka O, Ahmad F, Matsui T, Chin S, Wu P-H, Rybkin II, Shelton JM, Manieri M, Cinti S, Schoen FJ, Bassel-Duby R, Rosenzweig A, Ingwall JS and Spiegelman BM. Transcriptional coactivator PGC-1a controls the energy state and contractile function of cardiac muscle. Cell Metabolism 2005; 1:259-271.
2. Arany Z, Novikov M, Chin, S, Ma Y. Rosenzweig A and Spiegelman BM. Transverse aortic constriction leads to accelerated heart failure in mice lacking PGC-1a. Proc Natl Acad Sci USA 2006; 103:10086-10091.
3. Mootha VK, Handschin C, Arlow D, Xie X, St. Pierre J, Sihag S, Yang W, Altshuler D, Puigserver P, Willy PJ, Shulman IG, Heyman RA, Lander ES and Spiegelman BM. Erra and Gabpa?b specify PGC-1a-dependent OXPHOS gene expression that is altered in diabetic muscle. Proc Natl Acad Sci USA 2004; 101:6570-6575.
4. Wu Z, Puigserver P, Andersson U, Zhang C, Adelmant G, Mootha V, Troy A, Cinti S, Lowell B, Scarpulla R and Spiegelman BM. Mechanisms controlling mitochondrial biogenesis and respiration through the thermogenic coactivator PGC-1. Cell 1999; 98:115-124.
5. Puigserver P, Wu Z, Park CW, Graves R, Wright M and Spiegelman BM. A cold inducible coactivator of nuclear receptors linked to adaptive thermogenesis. Cell 1998; 92:829-839.

Last updated 10/19/2007.