Sarika Srivastava, Ph.D.
- Research Assistant Professor, Fralin Biomedical Research Institute at VTC
- Assistant Professor, Internal Medicine, Virginia Tech Carilion School of Medicine
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.
View a more complete list of Dr. Srivastava's publications at PubMed.
Mukherjee K, Patel PA, Rajan DS, LaConte LEW, Srivastava S. (2020). Survival of a male patient harboring CASK Arg27Ter mutation to adolescence. Mol Genet Genomic Med. Jul 21;:e1426.
Patel PA, Liang C, Arora A, Vijayan S, Ahuja S, Wagley PK, Settlage R, LaConte LEW, Goodkin HP, Lazar I, Srivastava S, Mukherjee K. (2020). Haploinsufficiency of X-linked intellectual disability gene CASK induces post-transcriptional changes in synaptic and cellular metabolic pathways. Exp Neurol. Jul;329:113319.
Srivastava S. (2019). Emerging Insights into the Metabolic Alterations in Aging Using Metabolomics. Metabolites 9(12): pii: E301. doi: 10.3390/metabo9120301.
McMillan RP, Stewart S, Budnick JA, Caswell CC, Hulver MW, Mukherjee K, Srivastava S. (2019). Quantitative Variation in m.3243A > G Mutation Produce Discrete Changes in Energy Metabolism. Scientific Reports 9(1).
LaConte LEW, Chavan V, Elias AF, Hudson C, Schwanke C, Styren K, Shoof J, Kok F, Srivastava S and Mukherjee K. (2018). Two microcephaly-associated novel missense mutations in CASK specifically disrupt the CASK-neurexin interaction. Hum Genet 137(3): 231-246.
Srivastava S. (2017). The mitochondrial basis of aging and age-related disorders. Genes (Basel) 8(12): pii: E398.
LaConte LEW, Srivastava S and Mukherjee K. (2017). Probing protein kinase-ATP interactions using a fluorescent ATP analog. Methods Mol Biol 1647: 171-183.
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.
Rudresh, Jain R, Dani V, Mitra A, Srivastava S, Sarma SP, Varadarajan R, Ramakumar S. (2002). Structural consequences of replacement of an alpha-helical Pro residue in Escherichia coli thioredoxin. Protein Eng 15(8): 627-33.
Moraes CT, Srivastava S, Kirkinezos I, Oca-Cossio J, van Waveren C, Woischnick M, Diaz F. (2002). Mitochondrial DNA structure and function. In: Int Rev Neurobiol. (pp. 3-23):Waltham, MA: Academic Press.
Srivastava S, Moraes CT. (2001). Manipulating mitochondrial DNA heteroplasmy by a mitochondrially targeted restriction endonuclease. Hum Mol Genet 10: 3093-99.
Ganesh C, Eswar N, Srivastava S, Ramakrishnan C, Varadarajan R. (1999). Prediction of the maximal stability temperature of monomeric globular proteins solely from amino acid sequence. FEBS Lett 454(1): 31-6.
Chakrabarti A, Srivastava S, Swaminathan CP, Surolia A, Varadarajan R. (1999). Thermodynamics of replacing an alpha-helical pro residue in the P40S mutant of Escherichia coli thioredoxin. Protein Sci 8(11): 2455-59.
- Harvard University School of Medicine: 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
- United Mitochondrial Disease Foundation (UMDF) Postdoctoral grant award, 2009 – 2011
- Seahorse Bioscience travel award, 2014
- Carilion Clinic Research Acceleration Program grant award, 2018 – 2019