BBS Faculty Member - Vamsi Mootha

Vamsi Mootha

Department of Systems Biology, HMS
Howard Hughes Medical Institute
Department of Molecular Biology, MGH
Metabolism Program, Broad Institute


Massachusetts General Hospital
Department of Molecular Biology
185 Cambridge St., CPZN 7250
Boston, MA 02114
Tel: 617-643-3059
Fax: 617-643-2335
Email: vamsi@hms.harvard.edu
Lab Members: 9 postdoctoral fellows, 8 graduate students, 4 technicians
Visit my lab page here.



Mitochondria are tiny organelles 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. Recent studies have implicated mitochondrial dysfunction in a variety of human diseases, including diabetes, cancer, neurodegeneration, and aging. My group 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 using experimental approaches that combine classic biochemistry with the new tools of genomics. We make chemical and genetic perturbations in cellular systems that can be systematically profiled using microarrays and tandem mass spectrometry. We are also developing computational and statistical techniques to integrate these vast datasets to link biological networks with measures of biochemical function. In this manner we hope to construct predictive models of mitochondrial remodeling that can then be validated with additional rounds of perturbation. Simultaneously, we are working in close collaboration with clinicians and geneticists to apply genome-scale profiling technologies to study human metabolic disorders. Currently our clinical studies are focused on mitochondrial respiratory chain diseases. By integrating the results from our in vitro experiments with those from our human studies, we hope to uncover the biological networks that are operative in human disease.






Last Update: 6/6/2014



Publications

For a complete listing of publications click here.

 


 

Pagliarini DJ, Calvo SE, Chang B, Sheth SA, Vafai SB, Ong SE, Walford GA, Sugiana C, Boneh A, Chen WK, Hill DE, Vidal M, Evans JG, Thorburn DR, Carr SA, Mootha VK. A mitochondrial protein compendium elucidates complex I disease biology. Cell 2008; 134(1):112-23. PMCID: PMC2778844

Perocchi F, Gohil VM, Girgis H, Bao R, McCombs J, Palmer A,
Mootha VK. MICU1 encodes a mitochondrial EF hand protein required for Ca2+ uptake. Nature 2010; 467(7313):291-6. PMCID: PMC2977980

Baughman JM, Perocchi F, Girgis HS, Plovanich M, Belcher-Timme CA, Sancak Y, Bao XR, Strittmatter L, Goldberger O, Bogorad RL, Koteliansky V,
Mootha VK. Integrative genomics identifies MCU as an essential component of the mitochondrial calcium uniporter, Nature 2011: 476(7360):341-5. PMCID: PMC21685886

Calvo SE, Compton AG, Hershman SG, Lim SC, Lieber DS, Tucker EJ, Laskowski A, Garone C, Liu S, Jaffe DB, Christodoulou J, Fletcher JM, Bruno DL, Goldblatt J, DiMauro S, Thorburn DR,
Mootha VK. Molecular diagnosis of infantile mitochondrial disease with targeted next-generation sequencing, Science Translational Medicine 2012: 4(118):118ra10. PMCID: PMC22277967

Jain M, Nilsson R, Sharma S, Madhusudhan N, Kitami T, Souza A, Kafri R, Kirschner MW, Clish CB,
Mootha VK. Metabolite profiling reveals a key role for glycine in rapid cancer cell proliferation, Science 2012: 336(6084): 1040-44. PMCID: PMC22628656



© 2013 by the President and Fellows of Harvard College