Vamsi K. Mootha, MD
Year elected: 2009
Current membership category: Active
Honors and awards
National Academy of Sciences (2014)
Our laboratory studies mitochondria. These tiny organelles are found in nearly all cells, serving as the center stage for ATP production, ion homeostasis, and apoptosis. Their composition, density, and coupling efficiency are dynamic properties, varying across cell types and adapting to changes in energetic status during growth and differentiation. Mitochondrial dysfunction can underlie a variety of human diseases, ranging from rare, inborn errors of metabolism to common degenerative disease. Our lab is broadly interested in characterizing the structure and dynamic properties of the biological networks underlying mitochondrial function, linking variation in these parameters to genetic variation, and exploiting the network properties of the organelle to design therapies for human disease. To achieve these goals, we are combining classic biochemistry with the new tools of genomics. In recent years we have used protein mass spectrometry to define the ~1100 nuclear genes encoding the mitochondrial proteome. By combining this inventory with human genetics, we have been able to identify five genes underlying Mendelian mitochondrial disease. We are now using experimental and computational genomics to systematically define the function of these 1100 genes, and understand how they are organized into pathways and complexes. Finally, we have launched new efforts aimed at identifying drug-like compounds that modulate mitochondrial activity, as well as metabolic profiling studies designed to discover circulating biomarkers of mitochondrial disease. Our long-term goal is to use these large-scale biological approaches to establish a rationale approach to mitochondrial medicine.
Harvard Medical School, Massachusetts General Hospital (Primary)
Dennis A. Ausiello, MD is the representative at this institution.