Vamsi Mootha
Our laboratory focuses on mitochondria, these tiny organelles found in virtually all human cells, serving as the center stage for energy metabolism, ion homeostasis, and apoptosis. Their composition, copy number, and efficiency are dynamic properties, varying across cell types and remodeling during growth and differentiation. Mitochondrial dysfunction underlies rare, inborn errors of metabolism, as well as some of the most common human diseases, such as diabetes, cancer, and neurodegeneration. Given their importance in basic biology and clinical medicine, mitochondria represent an excellent "model" for basic and clinical systems biology.
Our group is broadly interested in characterizing the structure and dynamic properties of mitochondria, understanding how genetic variation influence mitochondrial physiology, and exploiting the network properties of the organelle to design therapies for human disease. To achieve these goals, we combine classic biochemistry and physiology with the new tools of genomics, proteomics, and chemical biology. In recent years, we have used mass spectrometry, microscopy, and computation to define the mitochondrial proteome (an inventory we call MitoCarta). We have subsequently coupled MitoCarta with human genetics to discover six Mendelian disease genes. We have used computational and comparative genomics in combination with RNAi screens to predict and validate the function of proteins involved in biosynthetic pathways as well as in calcium homeostasis.
Current areas of focus include: (1) nuclear:mitochondrial cross-talk in the control of mitochondrial biogenesis, (2) membrane biochemistry and biophysics of ion and metabolite transport, (3) next-gen sequencing and functional studies of human mitochondrial disease, (4) metabolomics approaches to mitochondrial function, and (5) chemical biology approaches to modulating mitochondrial copy number and function.
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About Dr. Mootha: Vamsi Mootha received a B.S. in Mathematical and Computational Sciences from Stanford University and an M.D. from the Harvard-MIT Division of Health Sciences and Technology. After completing his Internship and Residency in Internal Medicine at Brigham and Women’s Hospital, he conducted postdoctoral research at the Whitehead Institute at MIT. He is a past recipient of a MacArthur Fellowship and has been elected to the National Academy of Sciences.