Sarika Srivastava, Ph.D.
Research Assistant Professor
Mitochondria are dynamic organelles central to energy production, metabolism, signaling and apoptosis. Proper mitochondrial function is critical for the maintenance of cellular energy and metabolic homeostasis as well as for the activation of appropriate stress responses. A major bioenergetic function of mitochondria is to produce ATP through a process of oxidative phosphorylation (OXPHOS). Mitochondrial dysfunction caused by genetic mutations that impair OXPHOS or energy production leads to a clinical onset of mitochondrial disease in which the high-energy-demanding tissues such as the nervous system, skeletal muscle and heart are predominantly affected. The estimated prevalence of mitochondrial disease is ~ 1:5,000. Mitochondrial dysfunction also increases with age and is associated with several age-related disorders including neurodegenerative diseases, metabolic syndrome and cancer. Currently, there is no cure for mitochondrial disease or dysfunction. Sirtuins are a family of NAD+-dependent protein deacetylases/mono-ADP-ribosyl transferases that have been implicated in the regulation of metabolic and energy homeostasis, stress responses, cell survival and aging. My research is focused on understanding how mammalian sirtuins impact mitochondrial bioenergetics, function and metabolism in healthy and disease states by employing a multi-disciplinary approach that involves biochemical, cell biological and mouse modeling experiments. The long-term goal of my research is to understand and identify novel signaling pathways that can improve mitochondrial dysfunction during disease and aging.
Education and Training
- Harvard University: Postdoctoral fellowship, Cell Biology
- University of Miami School of Medicine: Postdoctoral fellowship, Cell Biology
- University of Miami School of Medicine: Ph.D., Molecular Cell and Developmental Biology
- Madurai Kamaraj University: M.S., Biotechnology
- Delhi University: B.S., Botany
- Postdoctoral fellowship, Department of Cell Biology, Harvard Medical School
Awards and Honors
- United Mitochondrial Disease Foundation Award, 2009-2011
- Seahorse Bioscience Travel Award, 2014
- Carilion Clinic Research Acceleration Program Grant Award, 2018-2019
- Srivastava S. (2017). The mitochondrial basis of aging and age-related disorders. Genes (Basel) 8(12): pii: E398.
- Srivastava S. (2016). Emerging therapeutic roles for NAD+ metabolism in mitochondrial and age-related disorders. Clin Transl Med 5(25).
- Srivastava S, McMillan R, Willis J, Clark H, Chavan V, Liang C, Zhang H, Hulver M and Mukherjee K. (2016). X-linked intellectual disability gene CASK regulates postnatal brain growth in a non-cell autonomous manner. Acta Neuropathol Commun 4(30).
- Mukherjee K, Clark HR, Chavan V, Benson EK, Kidd GJ and Srivastava S. (2016). Analysis of brain mitochondria using serial block-face scanning electron microscopy. J. Vis. Exp 113.
- Chavan V, Willis J, Walker S, Clark H, Liu X, Srivastava S and Mukherjee K. (2015). Majority of central presynaptic terminals are ATP-enriched but devoid of mitochondria. PLoS One 10(4).
- Srivastava S, Haigis MC. (2011). Role of sirtuins and calorie restriction in neuroprotection: Implications in Alzheimer’s and Parkinson’s diseases. Curr Pharm Des 17(31): 3418-33.
- Srivastava S, Diaz F, Iommarini L, Aure K, Lombes A, Moraes CT. (2009). PGC-1 alpha/beta induced expression partially compensates for respiratory chain defects in cells from patients with mitochondrial disorders. Hum Mol Genet 18: 1805-12.
- Srivastava S, Moraes CT. (2009). Cellular adaptations to oxidative phosphorylation defects in cancer. In: S.P. Apte and R. Sarangarajan (Ed.), Cellular Respiration and Carcinogenesis. (pp. 55-72).New York, NY: Humana Press.
- Srivastava S, Barrett, JN, Moraes, CT. (2007). PGC-1alpha/beta upregulation is associated with improved oxidative phosphorylation in cells harboring nonsense mtDNA mutations. Hum Mol Genet 16: 993-1005.
- Srivastava S, Moraes CT. (2005). Double-strand breaks of mouse mtDNA promote large deletions similar to multiple mtDNA deletions in humans. Hum Mol Genet 53: 893-902.