Pharmacology & Cancer Biology | Duke University Medical Center

Dr. Shirish Shenolikar

Shirish Shenolikar, Ph.D.
Professor of Pharmacology and Cancer Biology
Assistant Research Professor in Medicine

Duke University Medical Center
C133 LSRC
Box 3813
Durham, NC 27710

Phone: 919-681-6178
E-mail: sheno001@mc.duke.edu

Research Interests

Now that many major signaling pathways and the molecules involved have been identified, the challenge facing investigators in signal transduction research is to unravel the redundancy and cross-talk between signaling pathways that dictate the spatial and temporal communication between cells during events such as embryogenesis, immune surveillance, thought and memory. Our work attempts to define the physiological role of "signaling modules" formed by protein kinases and phosphatases that function through specific protein scaffolds to transduce signals and control protein phosphorylation, translation and transcription. Aberrations in these cell-mediated events have already been linked to human diseases such as cancer and diabetes. Thus, by unraveling the disease mechanisms, our studies hope to lead the way for the development of novel pharmacological therapies. The specific goal of our work is to gain a molecular understanding of signaling complexes, define the cellular constraints that dictate their subcellular localization and dynamics and investigate the genetics and physiology of such signaling modules. Training in this laboratory will expose students and fellows to protein biochemistry, structural biology, cell imaging, yeast and mouse genetics i.e. an interdisciplinary approach required for a full understanding of signal transduction by hormones, neurotransmitters and growth factors.

Publications

Brush, M.H., Weiser, D.C. and Shenolikar, S. (2003) The growth arrest and DNA damage-inducible protein GADD34 targets protein phosphatase-1a to the endoplasmic reticulum and promotes dephosphorylation of the a-subunit of eukaryotic translation initiation factor 2. Mol. Cell. Biol. 23: 1292-1303.

Terry-Lorenzo, R.T., Elliot, E., Weiser, D.C., Prickett, T.D., Brautigan, D.L. and Shenolikar, S. (2002) Neurabins recruit protein phosphatase-1 and inhibitor-2 to actin cytoskeleton. J.Biol.Chem. 277:46535-46543.

Shenolikar, S., Voltz, J.W., Minkoff, C.M., Wade, J.B. and Weinman, E.J. (2002) Targeted disruption of the mouse NHERF-1 gene promotes internalization of proximal tubule sodium-phosphate cotransporter type IIa and renal phosphate wasting. Proc. Natl. Acad. Sci. USA. 99: 11470-11475.

Terry-Lorenzo, R.T., Carmody, L.C., Voltz, J.W., Connor, J.H., Li, S., Smith, F.D., Milgram, S.L, Colbran, R.J. and Shenolikar, S. (2002) The neuronal actin-binding proteins, neurabin I and neurabin II, recruit specific isoforms of protein phosphatase-1 catalytic subunits. J. Biol. Chem. 277:27716-27724.

Oliver, C.J., Terry-Lorenzo, R.T., Christensen Bloomer, W.A., Li, S., Elliott, E., Brautigan, D.L., Colbran, R.J. and Shenolikar, S. (2002) Targeting protein phosphatase-1 to the actin cytoskeleton : Neurabin I/PP1 complex regulates cell morphology. Mol. Cell. Biol. 22:4690-4701.

Morishita, W., Connor, J.H., Xia, H., Quinlan, E.M., Shenolikar, S. and Malenka, R.C. (2001) Regulation of synaptic strength by protein phosphatase-1. Neuron 32:1133-1148.

Voltz, J.W., Weinman, E.J. and Shenolikar, S. (2001) Expanding the role of NHERF, a PDZ-domain containing protein adapter, to growth regulation. Oncogene 20:6309-6314.

Connor, J.H., Weiser, D.C., Li, S., Hallenbeck, J.M. and Shenolikar, S. (2001) Growth arrest and DNA damage-inducible protein GADD34 assembles a novel signaling complex containing protein phosphatase-1 and inhibitor-1. Mol. Cell. Biol. 21:6841-6850.

Shenolikar, S. and Weinman, E.J. (2001) NHERF : targeting and trafficking membrane proteins. Am. J. Physiology (Renal Physiol.). 280: F389-396.

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