Associate Professor of Pathology
The Haigis Lab
Harvard Medical School
240 Longwood Ave.
Boston, MA 02115
Lab Size: Greater than 10
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.
Laurent G., German NJ, Saha AK, de Boer VCJ, Davies M, Koves TR, Dephoure N, Fischer F, Boanca G, Vaitheesvaran B, Lovitch SB, Sharpe AH, Kurland IJ, Steegborn C, Gygi SP, Muoio DM, Ruderman NB, Haigis MC. SIRT4 coordinates the balance between lipid synthesis and catabolism by repressing malonyl-CoA decarboxylase. Molecular Cell. 2013; 50:686-698. PMID: 23746352
Jeong SM, Xiao C, Finley LW, Lahusen T, Souza AL, Pierce K, Li YH, Wang X, Laurent G, German NJ, Xu X, Li C, Wang RH, Lee J, Csibi A, Cerione R, Blenis J, Clish CB, Kimmelman A, Deng CX, Haigis MC. SIRT4 Has Tumor-Suppressive Activity and Regulates the Cellular Metabolic Response to DNA Damage by Inhibiting Mitochondrial Glutamine Metabolism. Cancer Cell. 2013; 23:450-463. PMID: 23562301
Finley LW, Lee J, Souza A, Desquiret-Dumas V, Bullock K, Rowe GC, Procaccio V, Clish CB, Arany Z, Haigis MC. Skeletal muscle PGC-1alpha mediates mitochondrial, but not metabolic, adaptation to calorie restriction. Proc Natl Acad Sci U S A. 2012; 109:2931-2936. PMID: 22308395
Finley LW, Carracedo A, Lee J, Souza A, Egia A, Zhang J, Teruya-Feldstein J, Moreira PI, Cardosa SM, Clish CB, Pandolfi PP, Haigis MC. SIRT3 opposes reprogramming of cancer cell metabolism through HIF1alpha destabilization. Cancer Cell. 2011; 19:416-428. PMID: 21397863.
Haigis MC, Yankner BA. The aging stress response. Mol. Cell. 2010; 40:333-344. PMID: 20965426.