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Tim Lezon, PhD

Group Leader of Systems Biology and Modeling, Assistant Professor of Computational and Systems Biology Computational Systems Biology

PhD in physics, The Pennsylvania State University

The single-target view of drug discovery is yielding to a systems-based view in which drugs are used in combinations to alter the behavior of specific and multiple pathways. This approach, called Quantitative Systems Pharmacology (QSP) requires the seamless integration of computational modeling and experiments. Among the computational challenges of QSP are identifying pathways relevant to disease and outlining the mechanistic details of those pathways. My lab is developing methods for inferring disease pathways from screening data, and is constructing mechanistic models of pathways that are central to the progression of cancer and other diseases. We are developing methods to predict the outcomes of phenotypic screens, including how cells will respond to combinations of two or more drugs.

  1. Dual role of mitochondria in producing melatonin and driving GPCR signaling to block cytochrome c release. Suofu Y, Li W, Jean-Alphonse FG, Jiao J, Khattar NK, Li J, Baranov SV, Leronni D, Mihalik AC, He Y, Cecon E, Wehbi V, Kim J, Heath BE, Baranova OV, Wang X, Gable M, Kretz E, Di Benedetto G, Lezon TR, Ferrando L, Larkin TM, Sullivan MLG, Yablonska S, Wang J, Minnigh MB, Guillaumet G, Suzenet F, Richardson RM, Poloyac S, Stolz DB, Jockers R, Witt-Enderby P, Carlisle DL, Vilardaga J-P, Friedlander RM. Proc. Natl. Acad. Sci. USA 114:E7997-E8006 (2017). PMID: 28874589
  2. "Connecting Neuronal Cell Protective Pathways and Drug Combinations in a Huntington's Disease Model through the Application of Quantitative Systems Pharmacology."Pei, F., H. Li, M. J. Henderson, S. A. Titus, A. Jadhav, A. Simeonov, M. C. Cobanoglu, S. H. Mousavi, T. Shun, L. McDermott, P. Iyer, M. Fioravanti, D. Carlisle, R. M. Friedlander, I. Bahar, D. L. Taylor, T. R. Lezon, A. M. Stern and M. E. Schurdak (2017). Sci Rep 7(1): 17803.
  3. Proteomic screening and lasso regression reveal differential signaling in insulin and insulin-like growth factor I pathways. Erdem C, Nagle AM, Casa AJ, Litzenburger BC, Wang Y, Taylor DL, Lee AV and Lezon TR. Molecular and Cellular Proteomics M115.057729 (2016, in press).
  4. Identifying and Quantifying Heterogeneity in High Content Analysis: Application of Heterogeneity Indices to Drug Discovery. Gough A, Chen N, Schurdak M, Shun TY, Lezon T, Boltz R, Reese C, Wagner J, Vernetti L, Grandis J, Lee A and Taylor DL. PLoS ONE 9:e102678 (2014). PMID: 4103836
  5. Evol and ProDy for bridging protein sequence evolution and structural dynamics. Bakan A, Dutta A, Mao W, Liu Y, Chennubhotla C, Lezon TR and Bahar I. Bioinformatics 30:2681-2683 (2014). PMID: 24849577
  6. Constraints imposed by the membrane selectively guide the alternating access dynamics of the glutamate transporter GltPh. Lezon TR and Bahar I. Biophys J 102:1331-1340 (2012). PMID: 22455916
  7. The effects of rigid motions on elastic network model force constants. Lezon TR. Proteins 80:1133-1142 (2012). PMID: 22228562
Primary Address
Biomedical Science Tower 3, 3501 Fifth Ave, Pittsburgh, PA 15213, USA
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