Iyengar Laboratory

Susana Neves, Ph.D.

Postdoctoral Fellow, Department of Pharmacology and Systems Therapeutics
E-mail: susana.neves@mssm.edu

Mailing Address

One Gustave L. Levy Place, Box 1215 New York NY 10029

Training and Education

Ph.D. (2006) Mount Sinai School of Medicine, New York, NY, USA

B.A. (1998) Rutgers University, New Brunswick, NJ, USA

Current Research

The cAMP pathway is one of the most ubiquitous signaling pathways. cAMP can be produced by a plethora of extracellular stimuli. cAMP levels are modulated by the opposing actions of adenylyl cyclase and phosphodiesterases. Once adenylyl cyclase is activated via a G-protein coupled receptor or by Ca++, the small diffusible 2nd messenger cAMP is produced and activates its targets. Neurons are probably one of the most complex cells in the organism. They receive a multitude of inputs into their very intricate dendritic harbor. They then have to weigh the inputs in a manner that allows the cell to integrate them and eventually make decisions. Based on this knowledge it is difficult to imagine that signaling components that are involved in the relaying of information are random groups of proteins that are free floating in a well-stirred mixture. The discovery of proteins, such as scaffolds in mammalian systems which function to provide platforms for enzymatic reactions to occur in the appropriate region of the cell, has led to the idea that the freely diffusible reactions in aqueous medium may not occur in the living cell. Morphogen gradients, as studied in the developmental field, (reviewed by (Gurdon & Bourillot 2001)) is a concept that can be applied to intracellular signal transduction. It has been established that the morphogen gradient is formed by the differential spatial distribution and regulation of the negative regulators (or inhibitors) of the morphogen(s). Recent findings suggest that intracellular cAMP is not homogenously distributed either through the cell, but it may be concentrated, in specific regions named microdomains. The microdomain themselves are likely to be dynamically regulated but the mechanisms underlying their regulation are not fully understood. The cAMP microdomains, similarly to the morphogen gradients, may be regulated by negative regulators, such as phosphodiesterases, which in turn are modulated by MAP kinase and PKA. This could also lead to the formation of PKA microdomains and MAP kinase microdomains, since these proteins are regulated in a cAMP dependent manner in neurons. The overall goal of this project is to determine the contribution of negative regulators, such as phosphodiesterases and phosphatases, in the regulation of the activation and localization of MAP kinase by the cAMP dependent activation of upstream kinases and the modulation of phosphatases. We are approaching this problem with the use of spatial modeling techniques supplemented by experimental data.

Publications

Pagano M, Jordan JD, Neves S, Nguyen T, Iyengar R. Galpha(o/i)-stimulated proteosomal degradation of RGS20: A mechanism for temporal integration of G(s) and G(i) pathways. Cell Signal. 2008 Feb 19.

Aaronson DS, Muller M, Neves S, Chung WC, Jayaram G, Iyengar R, Ram PT. An androgen-IL-6-Stat3 autocrine loop re-routes EGF signal in prostate cancer cells. Mol Cell Endocrinol. 2007 May 30;270(1-2):50-6.

He JC, Lu TC, Fleet M, Sunamoto M, Husain M, Fang W, Neves S, Chen Y, Shankland S, Iyengar R, Klotman PE. Retinoic acid inhibits HIV-1-induced podocyte proliferation through the cAMP pathway. J Am Soc Nephrol. 2007 Jan;18(1):93-102.

He JC, Neves S, Jordan JD, Iyengar R. Role of the Go/i signaling network in the regulation of neurite outgrowth. Can J Physiol Pharmacol. 2006 Jul;84(7):687-94.

Ma'ayan A, Jenkins SL, Neves S, Hasseldine A, Grace E, Dubin-Thaler B, Eungdamrong NJ, Weng G, Ram PT, Rice JJ, Kershenbaum A, Stolovitzky GA, Blitzer RD, Iyengar R. Formation of regulatory patterns during signal propagation in a Mammalian cellular network. Science. 2005 Aug 12;309(5737):1078-83.

Campagne F, Neves S, Chang CW, Skrabanek L, Ram PT, Iyengar R, Weinstein H, Quantitative information management for the biochemical computation of cellular networks. Sci STKE. 2004 Aug;(248):p|11.

Neves SR, Ram PT, Iyengar R. G protein pathways. Science 2002 May 31;296(5573):1636-9.

Neves S, Iyengar R. Modeling of signaling networks. Bioessays 2002 Dec;24(12):1110-7.

Presentations

2nd International Conference on Pathways, Networks, and Systems: Theory and Experiments, Crete, Greece - October 2004, Modeling the Dynamic Regulation of Signaling Microdomains.

2nd International Symposium on Computational Cell Biology, Lenox, MA - March 2003, Regulation of the Dynamics of Intracellular Microdomains of Signaling Molecules in Neurons.

Honors

NRSA Predoctoral Fellowship, Honors College, Garden State Scholar, Dean's List