The New York Center for Systems Biology (NYCSB) brings together researchers and educators from Mount Sinai SOM, Columbia University College of Physicians, Courant Inst of Mathematical Sciences NYU, SUNY Stony brook, City College CUNY and the IBM T.J Watson Research Lab to integrate theoretical and experimental approaches for a deep mechanistic understanding of multi-scale functional organization of mammalian physiological/pathophysiological systems and how drugs (therapeutic and abusive) affect this organization. We want to understand how the effects of molecular interactions are propagated across scales of organization from cells to tissues and organs affecting physiology and pathophysiology. We posit that the dynamic organization of motifs (regulatory loops) within multi-scale networks provides the basis for propagation of effects across scales from molecules to cells to tissues. Drugs have their effects by reorganizing network topology across these scales. We study selected processes in the heart and brain to test these hypotheses. We are developing and seamlessly integrating multiple modeling approaches including graph theory analysis, differential equation-based modeling and the new method of stochastic reaction-diffusion to model processes in 3D. Such theoretical integration allows us to construct and analyze multi-scale models. We are developing parallelized programs that run on supercomputers such as IBM Blue-Gene/L both for dynamic motif searches in large networks and for simulations of differential equation- based models. The theoretical studies are well integrated with multivariable experiments to profile activity changes by reverse protein arrays, transcription factor arrays and microarrays. The multivariable experiments in turn are combined with quantitative measurements of molecular interactions and tissue level physiological measurements to constrain models and test model predictions. The research activities of the NYCSB form a continuum with our educational and outreach activities that include graduate and postdoctoral training, summer programs for undergraduates with a focus on recruiting underrepresented minorities, training undergraduate educators, personalized workshops and opportunities to participate in the NYCSB research projects for all researchers. Together these research, education and outreach activities will allow NYSBC make significant contributions towards the development of Systems Medicine and Therapeutics.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Specialized Center (P50)
Project #
3P50GM071558-05S1
Application #
8529785
Study Section
Special Emphasis Panel (ZGM1-CBCB-2 (SB))
Program Officer
Dunsmore, Sarah
Project Start
2007-09-18
Project End
2013-08-31
Budget Start
2011-09-01
Budget End
2013-08-31
Support Year
5
Fiscal Year
2012
Total Cost
$461,607
Indirect Cost
$188,467
Name
Icahn School of Medicine at Mount Sinai
Department
Pharmacology
Type
Schools of Medicine
DUNS #
078861598
City
New York
State
NY
Country
United States
Zip Code
10029
Ron, Amit; Azeloglu, Evren U; Calizo, Rhodora C et al. (2017) Cell shape information is transduced through tension-independent mechanisms. Nat Commun 8:2145
Xiong, Yuguang; Soumillon, Magali; Wu, Jie et al. (2017) A Comparison of mRNA Sequencing with Random Primed and 3'-Directed Libraries. Sci Rep 7:14626
Hansen, Jens; Meretzky, David; Woldesenbet, Simeneh et al. (2017) A flexible ontology for inference of emergent whole cell function from relationships between subcellular processes. Sci Rep 7:17689
Stern, Alan D; Rahman, Adeeb H; Birtwistle, Marc R (2017) Cell size assays for mass cytometry. Cytometry A 91:14-24
Flamini, Vittoria; DeAnda, Abe; Griffith, Boyce E (2016) Immersed boundary-finite element model of fluid-structure interaction in the aortic root. Theor Comput Fluid Dyn 30:139-164
Smith, Gregory R; Birtwistle, Marc R (2016) A Mechanistic Beta-Binomial Probability Model for mRNA Sequencing Data. PLoS One 11:e0157828
Leffler, Shoshana R; Legué, Emilie; Aristizábal, Orlando et al. (2016) A Mathematical Model of Granule Cell Generation During Mouse Cerebellum Development. Bull Math Biol 78:859-78
Krogh-Madsen, Trine; Sobie, Eric A; Christini, David J (2016) Improving cardiomyocyte model fidelity and utility via dynamic electrophysiology protocols and optimization algorithms. J Physiol 594:2525-36
Lee, Young-Seon; Hwang, Minki; Song, Jun-Seop et al. (2016) The Contribution of Ionic Currents to Rate-Dependent Action Potential Duration and Pattern of Reentry in a Mathematical Model of Human Atrial Fibrillation. PLoS One 11:e0150779
Bouhaddou, Mehdi; DiStefano, Matthew S; Riesel, Eric A et al. (2016) Drug response consistency in CCLE and CGP. Nature 540:E9-E10

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