Faculty


Sriram Chandrasekaran

Assistant Professor of Biomedical Engineering

Junior Fellow, Harvard Society of Fellows, Harvard University
Ph.D. Biophysics, University of Illinois at Urbana-Champaign
B.Tech, Biotechnology, Anna University, Chennai, India

Research Focus: Systems biology; computational biology; metabolic regulation; chemogenomics; antibiotics; drug resistance

Phone: 734.764.1566
E-mail: csriram@umich.edu

Our lab develops computer models to understand how complex networks in a cell – spanning metabolism, gene regulation and signaling – interact with each other, how these networks break down in disease, and how they can be targeted for therapy using drug combinations. We address this challenge by developing theoretical models that incorporate principles from chemistry (thermodynamics, stoichiometry) and engineering (such as mass and energy balance) to simulate the dynamic regulation of metabolic pathways.

The computational approaches that we have developed (PROM, ASTRIX and GEMINI) perform complementary functions in reconstruction and modeling of biological networks. For instance, the popular genome-scale modeling tool – PROM that we developed integrates metabolic networks with transcriptional regulatory networks. PROM was used to identify key regulators of metabolic pathways in the pathogen M. tuberculosis. Modeling this interplay between metabolic pathways and regulatory processes holds promise for dissecting the impact of diet, genetics and environment on human health.

Another major focus of our lab is to apply systems approaches to understand antibiotic resistance and subsequently design combination therapies for infectious diseases like Tuberculosis. We are using chemogenomics data and computational models to design effective combination therapies that have enhanced efficacy, diminished side effects, and reduced potential for developing drug resistance.



Chandrasekaran Research Group

 

Representative Publications

  1. Chandrasekaran S and N.D. Price, "Probabilistic integrative modeling of genome-­ scale metabolic and regulatory networks in Escherichia coli and Mycobacterium tuberculosis," PNAS, 2010

  2. Chandrasekaran S, Ament S.A, Eddy J.A, Rodriguez-­Zas S.R, Schatz B.R, Price N.D, and Robinson G.E, "Behavior-­specific changes in transcriptional modules lead to distinct and predictable neurogenomic states", PNAS, 2011

  3. Chandrasekaran S and Price ND, “Metabolic Constraint-­based Refinement of Transcriptional Regulatory Networks”, PLOS Computational Biology, 2013.

  4. Chandrasekaran S, Cokol-Cakmak M, Sahin N, Yilancioglu K, Kazan H, Collins J.J and Cokol M, “Chemogenomics and Orthology-based Design of Antibiotic Combination Therapies” Molecular Systems Biology, 2016.

  5. Chandrasekaran S*, Zhang J*, Ross C, Huang Y, Asara JM, Li H, Daley GQ, Collins JJ. Comprehensive mapping of pluripotent stem cell metabolism using dynamic genome-scale network modeling, Cell Reports (in press), 2017

 

 

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