Assistant Professor of Pathology
Harvard Medical School
NRB-954C
77 Ave Louis Pasteur
Boston, MA 02115
PH: 617-432-6865
FX: 617-432-6562
marcia_haigis@hms.harvard.edu

Lab Website

Research Interests

Our laboratory focuses on understanding the role that mitochondria play in mammalian aging and disease. Mitochondria are dynamic organelles that provide cells with energy even during dramatic changes in diet, stress and development. Mitochondria are also a major site for reactive oxygen species production, ion homeostasis, and apoptosis. Not surprisingly, mitochondrial dysfunction has been implicated in aging, neurodegeneration and metabolic diseases, such as diabetes.

 The regulation of aging is highly conserved. For example, an extra copy of SIR2 (silent information regulator; sirtuins) significantly increases the lifespan of yeast, worms and flies. Mammals have seven homologs of SIR2, three of which are found in mitochondria. Recent studies have shown that sirtuins affect mitochondrial biogenesis and energy production. Our lab is interested in understanding how sirtuins mediate the interplay between mitochondrial activity and aging.

 The main goals of our research are: 1) to identify signals generated by mitochondria that contribute to aging and to identify those regulated by mammalian sirtuins, 2) to determine molecular mechanisms for these signals, and 3) to understand how these pathways regulate biological functions that decline during normal aging. To accomplish these goals, our research integrates biochemistry, proteomics, cell biology and mouse genetics. These studies have the potential to lead to novel therapies that could treat a spectrum of human diseases.

Publications

1. Haigis MC, Mostoslavsky R, Haigis KM, Fahie K, Christodoulou DC, Murphy AJ, Valenzuela DM,  Yancopoulos GD, Karow M, Blander G, Wolberger C, Prolla TA, Weindruch R, Alt FW, Guarente L. SIRT4 inhibits glutamate dehydrogenase and opposes the effects of calorie restriction in pancreatic beta cells. Cell 2006; 126:941-54.

2. Haigis MC and Guarente L. Mammalian sirtuins – emerging roles in physiology, aging and calorie restriction, Genes and Development 2006; 20:2913-21.

3. Lin SJ, Ford E, Haigis MC, Liszt G, Guarente L. Calorie restriction extends yeast life span by lowering the level of NADH. Genes and Development 2004; 18:12-16.

4. Leissring M, Farris W, Wu, Christodoulou D, Haigis MC, Guarente L, Selkoe D. Alternative translation initiation generates a novel isoform of insulin-degrading enzyme targeted to mitochondria. Biochemical Journal 2004; 116:313-24.