Photo of Srinivas (Ravi) Iyengar

Srinivas (Ravi) Iyengar

  • PROFESSOR Pharmacology and Systems Therapeutics
  • DIRECTOR SYSTEMS BIOLOGY CENTER NEW YORK
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Education

  • B.S., Bombay University
    Major-Chemistry, Minor-Physics

  • M.Sc., Bombay University
    Biophysics

  • M.S., University of Houston
    Biophysics

  • Ph.D., University of Houston
    Biophysical Sciences

  • Fellowship, Baylor College of Medicine

Biography

Research

Summary of Research

The Iyengar laboratory is interested in understanding how signals are routed and processed through cellular signaling networks including mechanisms of information sorting and integration.

We are interested in understanding dynamics of network topology. For this we focus on identifying regulatory motifs such as feedback and feedforward loops and determining their information processing capability. We have constructed and analyzed dynamic maps of these motifs to understand how cellular signaling networks engage the various cellular machinery to produce physiological responses to extra-cellular signals. To study complex cell signaling networks we utilize a combination of experimental and theoretical approaches. Multidimensional experimental approaches currently being used in the laboratory include reverse-phase phosphoproteomic arrays, transcription factor arrays, ChIP-Seq and mRNA profiling by sequencing. These experimental approaches are being integrated with theoretical analysis using both graph theory approaches and differential equation based modeling to understand network regulation of cell proliferation and activity induced synaptic plasticity.

We are interested in understanding how spatial organization within cells and tissues contributes to dynamic stability. We are studying the role of cell shape in regulating information processing within signaling networks. For these studies at the experimental level we are using approaches to observe and quantify biochemical signaling reactions in live cells. We are also using patterned surfaces at the nano and microscale as to obtain cells of specific shapes that can be imaged. To decipher the information content in cell shape we are analyzing signaling networks using partial differential equations. We are developing spatially realistic models of signaling networks to understand the origins and dynamics of microdomains of signaling components. We are also interested in understanding the dynamics underlying tissue integrity. We are developing multi-scale models as well as experimentally engineered systems to determine if a dynamic loop that integrates signaling networks in multiple cell types forms the basis for tissue integrity.

We are developing systems level approaches to understanding drug action at a genome-wide level. We are constructing large scale networks to capture all of the known protein-protein interactions in the human genome to computationally identify selective regions (disease neighborhood) within the interaction space associated with specific diseases. We are analyzing the relationship between drug targets and other cellular components to understand the relationship between disease neighborhood and targets of drugs used to treat the disease. From such analyses we are attempting to predict adverse events and explain adverse events reports in the FDA–AERS database.

For more information, please visit the Iyengar Laboratory, Systems Pharmacology and Systems Biology website.

Publications

Azeloglu EU, Hardy SV, Eungdamrong NJ, Chen Y, Jayaraman G, Chuang PY, Fang W, Xiong H, Neves SR, Jain MR, Li H, Ma'ayan A, Gordon RE, He JC, Iyengar R. Interconnected network motifs control podocyte morphology and kidney function. Science Signaling 2014; 7(311).

Zhao S, Nishimura T, Chen Y, Azeloglu EU, Gottesman O, Giannarelli C, Zafar MU, Benard L, Badimon JJ, Hajjar RJ, Goldfarb J, Iyengar R. Systems Pharmacology of Adverse Event Mitigation by Drug Combinations. Science Translational Medicine 2013 Oct; 5(206).

Rangamani P, Lipshtat A, Azeloglu EU, Calizo RC, Hu M, Ghassemi S, Hone J, Scarlata S, Neves SR, Iyengar R. Decoding information in cell shape. Cell 2013 Sep; 154(6).

Iyengar R, Zhao S, Chung SW, Mager DE, Gallo JM. Merging systems biology with pharmacodynamics. Science Translational Medicine 2012 Mar; 4(126).

Rangamani P, Fardin MA, Xiong Y, Lipshtat A, Rossier O, Sheetz MP, Iyengar R. Signaling network triggers and membrane physical properties control the actin cytoskeleton-driven isotropic phase of cell spreading. Biophysical Journal 2011 Feb; 100(4): 845-857.

Xiong Y, Rangamani P, Fardin MA, Lipshtat A, Dubin-Thaler B, Rossier O, Sheetz MP, Iyengar R. Mechanisms controlling cell size and shape during isotropic cell spreading. Biophysical Journal 2010 May; 98(10): 2136-2146.

Berger SI, Ma'Ayan A, Iyengar R. Systems pharmacology of arrhythmias. Science Signaling 2010 Apr; 3(118): ra30.

Lipshtat A, Jayaraman G, He JC, Iyengar R. Design of versatile biochemical switches that respond to amplitude, duration, and spatial cues. Proc Natl Acad Sci U S A 2010 Jan; 107(3): 1247-1252.

Ma'ayan A, Cecchi GA, Wagner J, Rao AR, Iyengar R, Stolovitzky G. Ordered cyclic motifs contribute to dynamic stability in biological and engineered networks. Proc Natl Acad Sci U S A 2008 Dec; 105(49): 19235-19240.

Neves SR, Tsokas P, Sarkar A, Grace EA, Rangamani P, Taubenfeld SM, Alberini CM, Schaff JC, Blitzer RD, Moraru II, Iyengar R. Cell shape and negative links in regulatory motifs together control spatial information flow in signaling networks. Cell 2008 May; 133(4): 666-680.

Bromberg KD, Ma'ayan A, Neves SR, Iyengar R. Design logic of a cannabinoid receptor signaling network that triggers neurite outgrowth. Science 2008 May; 320(5878): 903-909.

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; 309(5737): 1078-1083.

Industry Relationships

Physicians and scientists on the faculty of the Icahn School of Medicine at Mount Sinai often interact with pharmaceutical, device and biotechnology companies to improve patient care, develop new therapies and achieve scientific breakthroughs. In order to promote an ethical and transparent environment for conducting research, providing clinical care and teaching, Mount Sinai requires that salaried faculty inform the School of their relationships with such companies.

Below are financial relationships with industry reported by Dr. Iyengar during 2012 and/or 2013. Please note that this information may differ from information posted on corporate sites due to timing or classification differences.

Consulting:

  • F. Hoffman-La Roche Ltd.

Scientific Advisory Board:

  • GlaxoSmithKline

Mount Sinai's faculty policies relating to faculty collaboration with industry are posted on our website at http://icahn.mssm.edu/about-us/services-and-resources/faculty-resources/handbooks-and-policies/faculty-handbook. Patients may wish to ask their physician about the activities they perform for companies.

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