Supriya Srinivasan, PhD

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.

Lee BH, Liu J, Wong D, Srinivasan S, Ashrafi K. Hyperactive Neuroendocrine Secretion Causes Size, Feeding, and Metabolic Defects of C. elegans Bardet-Biedl Syndrome Mutants. PLoS Biol. 2011;9(12):e1001219.

Srinivasan S, Sadegh L, Elle IC, Christensen AG, Faergeman NJ, Ashrafi K. Serotonin regulates C. elegans fat and feeding through independent molecular mechanisms. Cell Metab. 2008;7(6):533-44.

Conklin BR, Hsiao EC, Claeysen S, Dumuis A, Srinivasan S, Forsayeth JR, Guettier JM, Chang WC, Pei Y, McCarthy KD, Nissenson RA, Wess J, Bockaert J, Roth BL. Engineering GPCR signaling pathways with RASSLs. Nat Methods. 2008;5(8):673-8.

Srinivasan S, Santiago P, Lubrano C, Vaisse C, Conklin BR. Engineering the melanocortin-4 receptor to control constitutive and ligand-mediated G(S) signaling in vivo.PLoS One. 2007;2(7):e668.

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

Srinivasan S, Lubrano-Berthelier C, Govaerts C, Picard F, Santiago P, Conklin BR, Vaisse C. 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. 2004;114(8):1158-64.

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

Srinivasan S, Vaisse C, Conklin BR. Engineering the melanocortin-4 receptor to control G(s) signaling in vivo. Ann N Y Acad Sci. 2003;994):225-32.

Srinivasan S, Traini M, Herbert B, Sexton D, Harry J, Alexander H, Williams KL, Alexander S. Proteomic analysis of a developmentally regulated secretory vesicle.Proteomics. 2001;1(9):1119-27.

Srinivasan S, Griffiths KR, McGuire V, Champion A, Williams KL, Alexander S. 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. 2000;146 ( Pt 8):1829-39.

Srinivasan S, Alexander H, Alexander S. Crossing the finish line of development: regulated secretion of Dictyostelium proteins. Trends Cell Biol. 2000;10(6):215-9.

Srinivasan S, Alexander H, Alexander S. The Dictyostelium fruiting body - a structure of cells and cellulose. Trends Cell Biol. 2000;10(8):315.

Mreyen M, Champion A, Srinivasan S, Karuso P, Williams KL, Packer NH. Multiple O-glycoforms on the spore coat protein SP96 in Dictyostelium discoideum. Fuc(alpha1-3)GlcNAc-alpha-1-P-Ser is the major modification. J Biol Chem. 2000;275(16):12164-74.

Srinivasan S, Alexander H, Alexander S. The prespore vesicles of Dictyostelium discoideum. Purification, characterization, and developmental regulation. J Biol Chem. 1999;274(50):35823-31.