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Scripps Research Joint Appointments

Assistant Professor, Dorris Neuroscience Center
Department of Molecular and Experimental Medicine
Faculty, Kellogg School of Science and Technology

Research Focus

Laboratory of Molecular Physiology and Chemical Genetics

Our laboratory is interested in understanding emergent properties of complex biological networks at a molecular level. Specifically, we are interested in determining how adaptive homeostatic or allostatic properties such as energy balance and metabolic set points arise in complex multicellular animals, and in the multitude of extrinsic and intrinsic parameters that influence such properties during the lifespan of an animal. Implicit in our studies is the goal of finding new preventive and therapeutic strategies for the human diseases of metabolic dysregulation such as obesity and accelerated aging.

We employ the nematode C. elegans for our studies, an ideal model for systems-level analyses of energy balance networks and metabolic set-point regulation. We utilize a multidisciplinary approach using chemical biology, molecular genetics, proteomics and lipid profiling, pharmacology and neuroscience. The power of the C. elegans system allows the rapid discovery of new pathways that connect sensory function in the nervous system and other tissues, to metabolic actions in the periphery. Novel and conserved molecular candidates emerging from these studies will be tested in mammalian models. Our long-term goal is to understand the relative contributions of genetic, behavioral and environmental influences on complex physiological phenotypes.

Education

B.S., Biology, Macquarie University, 1996
Ph.D., Genetics, University of Missouri-Columbia, 2000

Professional Experience

1996 – 2000: Ph.D., Dr. Stephen Alexander's laboratory, Division of Biological Sciences, University of Missouri-Columbia, MO
2001-2005: Postdoctoral Fellow, Dr. Bruce Conklin’s laboratory, Gladstone Institutes, San Francisco, CA
2005-2009: Postdoctoral Fellow, Dr. Kaveh Ashrafi’s laboratory, Department of Physiology, UCSF, CA
                 Co-mentor: Dr. Keith Yamamoto, Department of Cellular and Molecular Pharmacology, UCSF, CA
2010-present: Assistant Professor, Department of Chemical Physiology, The Scripps Research Institute, La Jolla, CA

Awards & Professional Activities

National Institutes of Health - K99/R00 "Pathway to Independence" Fellow-to-Faculty Transition Award, 2007-2012
Ellison Medical Foundation/American Federation for Aging Research - Senior Postdoctoral Fellowship, 2005-2007
American Heart Association - Postdoctoral Fellowship, 2002-2005
Australian Postgraduate Award - Predoctoral Fellowship, 1996-1999 (declined)

Selected References

Srinivasan, S., Sadegh, L. and Ashrafi, K. (2008) Serotonin Regulates C. elegans fat and feeding through independent molecular mechanisms. Cell Metabolism7:533-544.

Conklin, B.R., Hsiao, E.C., Claeysen, S., Dumuis, A., Srinivasan, S., Forsayeth, J.R., Guettier, J.M., Chang, W.C., Pei, Y., McCarthy, K.D., Nissenson, R.A., Wess, J., Bockaert, J. and Roth, B.R. (2008) Engineering new signaling pathways with receptors activated solely by synthetic ligands (RASSLs) Nature Methods, 5:673-678.

Srinivasan, S., Lubrano, C., Santiago, P., Vaisse, C. and Conklin, B.R. (2007) Engineering the melanocortin-4 receptor to control constitutive and ligand-mediated G_s signaling in vivo” PLOS ONE 2:e668.

Srinivasan, S., Lubrano-Berthelier, C., Govaerts, C., Picard, F., Santiago, P., Conklin, B.R. and Vaisse, C. (2004) Constitutive activity of the melanocortin-4 receptor is maintained by its N-terminal domain and plays a role in energy homeostasis in humans. J Clin Invest 114(8):1158-64.

Govaerts, C., Srinivasan, S., Shapiro, A., Zhang, S., Picard, F., Clement, K., Lubrano-Berthelier, C., and Vaisse, C. (2005) Obesity-associated mutations in the melanocortin-4 receptor provide novel insights into its function. Peptides 26(10):1909-19.

Alexander, S., Srinivasan, S. and Alexander, H. (2003) Proteomics opens doors to the mechanisms of developmentally regulated secretion Mol Cell Proteomics 2(11):1156-63. 

Srinivasan, S., Vaisse, C. and Conklin, B.R. (2002) Engineering the Melanocortin-4 receptor as a tool to study Gs signaling in vivo. Ann New York Acad Sci 994:225-232. 

Srinivasan, S., Traini, M., Herbert, B., Sexton, D., Harry, J., Alexander, H., Williams, K. and Alexander, S. (2001) Proteomic analysis of a developmentally regulated secretory vesicle. Proteomics 1:1119-27. 

Srinivasan, S., Griffiths, K. R., McGuire, V., Champion, A., Williams, K. L. and Alexander, S. (2000) The cellulose-binding activity of the PsB multiprotein complex is required for proper assembly of the spore coat and spore viability in Dictyostelium discoideum. Microbiology 146:1829–39. 

Srinivasan, S., Alexander, H. and Alexander, S. (2000) Crossing the finish line of development: Regulated secretion of Dictyostelium proteins. Trends Cell Biol 10: 215–9. 

Srinivasan, S., Alexander, H. and Alexander, S. (2000) The Dictyostelium fruiting body—A structure of cells and cellulose. Trends Cell Biol 10:315.

Mreyen, M., Champion, A., Srinivasan, S., Karuso, P., Williams, K.L. and Packer, N.H. (2000) Multiple O-glycoforms on the spore coat protein SP96 in Dictyostelium discoideum: Fuc(a1-3)GlcNAc- a -1-P-Ser is the major modification. J Biol Chem 275: 12164–74. 

Srinivasan, S., Alexander, H. and Alexander, S. (1999) The prespore vesicles of Dictyostelium discoideum: Purification, characterization and developmental regulation. J Biol Chem 274: 35823–31. 

Links

Srinivasan Lab Website