Faculty

Chair
	412-648-3333 bahar@pitt.edu Office: 3058 BST3 Lab Website	Ivet Bahar, PhD - Distinguished Professor and John K. Vries Chair, Department of Computational & Systems Biology Ph.D. in Chemistry, Istanbul Technical Institute; B.S. and M.S. in Chemical Engineering, Bogazici U. Biomolecular systems are not static: they constantly move, change shape, and interact with each other. Understanding the mechanisms of their interactions and their binding, catalytic and allosteric signaling effects is not possible without a molecular level modeling of their collective dynamics. A major research goal in my lab is to investigate the dynamics of molecular systems in the cellular environment cellular using fundamental principles of physical sciences and engineering. Another is the development of novel quantitative molecular and system pharmacology tools toward discovering novel drugs or repurposing existing drugs, with focus on neurosignaling disorders. Cheng MH, Torres-Salazar D, Gonzalez-Suarez AD, Amara SG, Bahar I (2017) Substrate Transport and Anion Permeation Proceed through Distinct Pathways in Glutamate Transporters. ELife. 6: e25850 Cheng MH, Garcia-Olivares J, Wasserman S, DiPietro J, Bahar I (2017) Allosteric Modulation of Human Dopamine Transporter Activity under Conditions Promoting its Dimerization. J Biol Chem. 292: 12471-12482
	412-648-3315 benos@pitt.edu Office: 3059 BST3 Lab Website	Panayiotis (Takis) V. Benos, PhD - Professor, Vice Chair of Faculty Affairs Molecular Biology, University of Crete, 1997 Our ultimate goal is to investigate the causes of chronic diseases and cancer by using all available data. Our work involves the development of new machine learning methods for the integration of multi-modal, large, biomedical datasets in a probabilistic graphical framework. For this purpose we collaborate with many clinical researchers in the University of Pittsburgh and elsewhere. Oltvai ZN, Beckwitt CH, Warita K, Wells K, Benos PV, Raghu V (2018) Biomarker identifica­tion for statin sensitivity of cancer cell lines Biochem. Biophys. Res. Comm.. 495: 659-665 Pociask DA, Robinson KM, Chen K, McHugh KJ, Clay ME, Huang GT, Benos PV, Janssen-Heininger YM, Kolls JK, Anathy V, Alcorn JF (2017) Epigenetic and Transcriptomic Regulation of Lung Repair during Recovery from Influenza Infection. Am J Pathol. 187(4): 851-863
	412-648-8171 faeder@pitt.edu Office: 3082 BST3 Lab Website	James R. Faeder, PhD - Associate Professor, Vice Chair for Educational Programs/Initiatives Ph.D. in Chemical Physics, University of Colorado at Boulder I am interested in developing mathematical models of biological regulatory processes that integrate specific knowledge about protein-protein interactions. My current research includes the development of specific models of signal transduction and the development of new stochastic simulation algorithms that will greatly broaden the scope of models that can be developed. Other research areas include model reduction, parameter estimation and uncertainty analysis, and automated model construction from databases of protein interactions. Singh M, Oltvai ZN, Warita K, Warita T, Faeder JR, Lee REC, Sant S (2018) Shift from Sto-chastic to spatially-ordered expression of serine-glycine synthesis enzymes in 3D microtumors Sci. Rep. 8:9388: Morel PA, Lee REC, Faeder JR (2017) Demystifying the cytokine network: Mathematical models point the way Cytokine. 98: 115-123
Faculty
	412-648-8646 jayoob@pitt.edu Office: 3053 BST3 Lab Website	Joseph C. Ayoob, PhD - Associate Professor Ph.D., Neuroscience, Johns Hopkins University School of Medicine Research: As an experimentalist, I use molecular-genetic approaches to study developmentally-regulated cell death and engulfment. Studying this process during the development of an organism will give us new insights into how this same process also eliminates pre-cancerous cells in the adult. Training and Outreach: To reach out to and train the next generation of scientists, we have initiated Tiered Mentoring and Training programs for undergraduates (TECBio REU @ Pitt) and high school students (DiSCoBio Summer Academy) to prepare them for careers in STEM (see Education page for more info). Delubac D, Highley CB, Witzberger-Krajcovic M, Ayoob JC, Furbee EC, Minden JS, Zappe S (2012) Microfluidic system with integrated microinjector for automated Drosophila embryo injection. Lab Chip. 12(22): 4911-9. [JIF=6.260] Ayoob JC, Chennubhotla CS (2012) First Steps: Tomorrow's Scientists International Innovation, North America - The Future of American Research. May: 30-32
	412-624-1223 jberg@pitt.edu Lab Website	Jeremy M. Berg, PhD - Professor Ph.D. in Chemistry, Harvard University Specific interactions between macromolecules are key to essentially all biological processes. Our research program has two related goals. The first is to understand the structural and chemical bases by which these specific interactions occur. The second is to understand why, biologically and evolutionarily, particular interactions have the strengths that they do. Systems of particular interest involve peroxisomal protein targeting and protein and nucleic acid interactions involving zinc-binding domains. Jeremy M. Berg is Director of the Institute of Personalized Medicine, Associate Vice Chancellor for Science Strategy and Planning in the Health Sciences, and Professor of Computational and Systems Biology at the University of Pittsburgh. Berg JM, Berg WA (2016) No myth: Benefits of breast screening Nature. 529(7586): 283 Geskin A, Legowski E, Chakka A, Chandran UR, Barmada MM, LaFramboise WA, Berg JM, Jacobson RS (2015) Needs Assessment for Research Use of High-Throughput Sequencing at a Large Academic Medical Center PloS. 10: e0131166
	412-648-7776 ccamacho@pitt.edu Office: 3077 BST3 Lab Website	Carlos J. Camacho, PhD - Associate Professor Ph.D. in Physics, University of Maryland, College Park A striking set of specific and non-specific interactions encoded in the protein structure tolerates binding only to a unique substrate. My main research interests focus on modeling the physical interactions responsible for molecular recognition, and in the development of new technologies for structural prediction, their substrates and supramolecular assemblies. Any progress in these fundamental problems is bound to bring about a better understanding of how proteins work cooperatively in a cell, promoting breakthroughs in every aspect of the biological sciences. Ye Z, Needham PG, Estabrooks SK, Whitaker SK, Garcia BL, Misra S, Brodsky JL, Camacho CJ (2017) Symmetry breaking during homodimeric assembly activates an E3 ubiquitin ligase. Sci Rep. 7(1): 1789 Pabon NA, Camacho CJ (2017) Probing protein flexibility reveals a mechanism for selective promiscuity. eLife. 6: pii: e22889
	412-648-3335 anc201@pitt.edu Office: 3079 BST3 Lab Website	Anne Ruxandra Carvunis, PhD - Assistant Professor Ph.D., Bioinformatics, Université Joseph Fourier, Grenoble, France What makes each species unique? Why is it that drugs that cure rats in the lab are often powerless against human disease? A major goal of my research is to work out the molecular mechanisms of change and innovation in biological systems in order to define the genetic and network-level determinants of species-specificity. Domazet-Loso T, Carvunis AR, M. Mar, Sestak MS, Bakaric R, Neme R, Tautz D (2017) No evidence for phylostratigraphic bias impacting inferences on patterns of gene emergence and evolution Molecular Biology and Evolution. 34(4): 843-856 Carvunis AR, Wang T, Skola D, Yu A, Chen J, Kreisberg J, Ideker T (2015) Evidence for a common evolutionary rate in metazoan transcriptional networks ELife. 4: e11615
	412-648-7794 chakracs@pitt.edu Office: 3081 BST3 Lab Website	Chakra Chennubhotla, PhD - Associate Professor Ph.D. in Computer Science, University of Toronto Developing computational models and methods to improve the understanding of major interactions and allosteric mechanisms that underlie the proper functioning of biomolecular systems. In particular (i) developing information-theoretic concepts for determining the probabilistic rates, pathways, and sequences of information flow in multicomponent and cellular biomolecular systems, (ii) designing and interpreting FRET based experiments to explore and assess functional implications of molecular interactions and correlations, and (iii) developing novel computer vision methods for analyzing, refining and interpreting structure, dynamics, and function in biomolecular images and movies. Benos PV, Tosun BA, Manatakis DV, Vukmirovic M, Nguyen L, Yan X, Hu B, Deluliis G, Woolard T, Maya JD, Homer R, Kaminski N, Chennubhotla CS (2017) Towards Understanding Spatial Lung Tissue Heterogeneity In Idiopathic Pulmonary Fibrosis (IPF) A72. Mechanisms Driving Fibrosis. Narayanan C, Bernard DN, Bafna K, Choudhary OP, Chennubhotla CS, Agarwal PK, Doucet N (2017) Conformational Motions Impacting Function in an Enzyme Superfamily The FASEB Journal. 31(1 supplement): 762.6
	412-648-3338 mchikina@pitt.edu Office: 3078 BST3 Lab Website	Maria Chikina, PhD - Assistant Professor Ph.D. in Molecular Biology, Princeton University The rise of genome-scale experimental methods has greatly accelerated the speed of biological data accumulation. However, as datasets increase in size, it becomes easier to find patterns and correlations, but harder to distinguish true biological insight from technological and statistical artifacts. Consequently, exploiting large-scale datasets to inform our understanding of biological systems remains a challenge. My work has focused on bridging the gap between statistically rigorous computational techniques and knowledge of underlying biological and experimental processes to develop methods that overcome the biases and artifacts inherent in the structure of large-scale datasets and transform noisy data into concrete biological knowledge. Overacre-Delgoffe AE, Chikina M, Dadey RE, Yano H, Brunazzi EA, Shayan G, Horne W, Moskovitz JM, Kolls JK, Sander C, Shuai Y, Normolle DP, Kirkwood JM, Ferris RL, Delgoffe GM, Bruno TC, Workman CJ, Vignali DAA (2017) Interferon-γ Drives Treg Fragility to Promote Anti-tumor Immunity. Cell. 169(6): 1130-1141 Chikina M, Frieze A, Pegden W (2017) Assessing significance in a Markov chain without mixing. Proc Natl Acad Sci U S A.. 114(11): 2860-2864
	412-855-4562 nclark@pitt.edu Office: 3080 BST3 Lab Website	Nathan L. Clark, PhD - Associate Professor Ph.D. in Genome Sciences at University of Washington, Seattle Adaptive evolution brings about genetic changes in response to new challenges such as pathogens or a new environment. Our lab exploits genetic signatures left by these adaptations to determine mechanisms of functional change in proteins. In addition, we study the coevolutionary relationships between genes to infer new genetic interactions and to inform a systems-level view of the genome. Our overarching goal is to understand how proteins and their networks change over time, and we develop novel evolutionary tools to this end. Chikina M, Robinson JD, Clark NL (2016) Hundreds of Genes Experienced Convergent Shifts in Selective Pressure in Marine Mammals Mol Biol Evol.. 33(9): 2182–2192 Clancy CJ, Meslin C, Badrane H, Cheng S, Losada LC, Nierman WC, Vergidis P, Clark NL, Nguyen MH (2016) Candida albicans Transcriptional Profiling Within Biliary Fluid From a Patient With Cholangitis, Before and After Antifungal Treatment and Surgical Drainage Open Forum Infect Dis. 3: 3 ofw120
	412-383-5745 dkoes@pitt.edu Office: 3086 BST3 Lab Website	David R. Koes, PhD - Assistant Professor Ph.D. in Computer Science, Carnegie Mellon University Removing barriers to computational drug discovery bit by bit. I create novel computational methods for accelerating the pace of discovery and enhancing the accuracy of virtual screening. Koes DR, Vries JK (2017) Evaluating Molecular Mechanics Force Fields with a Quantum Chemical Approach Biophysical Journal. 112 (3): 289a Ragoza M, Hochuli J, Idrobo E, Sunseri J, Koes DR (2017) Protein-Ligand Scoring with Convolutional Neural Networks ournal of Chemical Information and Modeling. 57(4): 942-957
	412-648-8607 robinlee@pitt.edu Office: 3083 BST3 Lab Website	Robin E.C. Lee, PhD - Assistant Professor Ph.D. in Cellular and Molecular Medicine, University of Ottawa To decide between irreversible cell fates such as growth, differentiation or death, cells process information about their environment through a network of molecular circuits. Our research combines principles of systems and synthetic biology with large-scale data to understand how information flows through these circuits. By observing input-output relationships in the same cell using microfluidics, live-cell dynamics and single-molecule microscopy, we aim to decode the ‘language’ of signaling dynamics and develop mathematical models of information flow with single-cell resolution. Our ultimate goal is to understand how population-level responses emerge from single-cell heterogeneity and to rationally manipulate cell fate decisions in disease. Singh M, Oltvai ZN, Warita K, Warita T, Faeder JR, Lee REC, Sant S (2018) Shift from Sto-chastic to spatially-ordered expression of serine-glycine synthesis enzymes in 3D microtumors Sci. Rep. 8:9388: Morel PA, Lee REC, Faeder JR (2017) Demystifying the cytokine network: Mathematical models point the way Cytokine. 98: 115-123
	412-383-8042 lezon@pitt.edu Office: 3084 BST3 Lab Website	Tim Lezon, PhD - Assistant Professor Ph.D. in Physics, Pennsylvania State University My research focuses on identifying disease-specific pathways from phenotypic screens. Non-clonal cellular heterogeneity is a rich source of information on the molecular activity of cellular pathways, and I construct analytical and computational tools for extracting this information. The specific applications that I am focused on are developing targeted therapies for breast cancer, identifying combinations of drugs that will effectively treat Huntington’s disease, and advancing computational pathology through analysis of intratumor heterogeneity. Bergman S, Lezon T (2017) Modeling global changes induced by local perturbations to the HIV-1 capsid. J Mol Graphics Modelling. 71: 218-226 Gough A, Stern AM, Maier J, Lezon T, Shun TY, Chennubhotla SC, Schurdak ME, Haney SA, Taylor DL (2017) Biologically Relevant Heterogeneity: Metrics and Practical Insights. SLAS Discov.. (3): 213-237
	412-648-3333 oltvai@pitt.edu Office: 3087 BST3 Lab Website	Zoltan Oltvai, MD - Associate Professor of Pathology MD, Semmelweiss Medical University, Budapest Dr. Oltvai’s research interest is in the area of systems biology of cell metabolism, including the metabolism of prokaryotic and mammalian cells, including tumor cells. Dr. Oltvai is a staff pathologist in the Division of Clinical Microbiology. He is also a faculty member of the Interdisciplinary Biomedical Science Graduate Program, the Medical Scientist Training Program, the Cellular and Molecular Pathology Graduate Training Program, and the Joint CMU-Pitt PhD Program in Computational Biology. Ishikawa T, Hosaka , YZ , Beckwitt CH, Wells A, Oltvai ZN, Warita K (2018) Concomitant attenuation of HMG-CoA reductase expression potentiates the cancer cell growth-inhibitory effect of statins and expands their efficacy in tumor cells with epithelial characteristics. Oncotarget. 9: 29304-29315 Oltvai ZN, Beckwitt CH, Warita K, Wells K, Benos PV, Raghu V (2018) Biomarker identifica­tion for statin sensitivity of cancer cell lines Biochem. Biophys. Res. Comm.. 495: 659-665
	412-648-3338 dltaylor@pitt.edu Office: 10045 BST3 Lab Website	D. Lansing Taylor, PhD - Distinguished Professor; Director, University of Pittsburgh Drug Discovery Institute Ph.D. in Cell Biology, State University of New York at Albany My research interests have been rooted in understanding the temporal-spatial dynamics of signaling molecules and proteins in living cells, coupled to defining the mechanisms of fundamental cell functions such as cell division and cell migration. I have always integrated the development of new technologies in fluorescence-based reagents and light microscope imaging in order to improve the ability to define molecular events in cells and tissue models. My interests have evolved from single cell activities to understanding cellular population dynamics, including the biological basis for heterogeneity in response to perturbagens such as drug treatments. Tosun AB, Nguyen L, Ong N, Navolotskaia O, Carter G, Fine JL, Taylor DL, Chennubhotla SC (2017) Histological detection of high-risk benign breast lesions from whole slide images, Medical Image Computing and Computer Assisted Intervention (MICCAI ‘17), Quebec, Canada, September 10-14, 2017, Proceedings, part 2, pp. 1444-152 . Nguyen L, Tosun AB, Fine JL, Lee AV, Taylor DL, Chennubhotla SC (2017) Spatial statistics for segmenting histological structures in H&E stained tissue images. IEEE Trans Med Imaging. 36(7): 1522-1532
	412-383-5856 avogt@pitt.edu Office: 10047 BST3 Lab Website	Andreas Vogt, PhD - Associate Professor Ph.D. in Pharmaceutical Chemistry, University of Hamburg My major research interest is the discovery of new therapeutic agents for diseases related to cell proliferation and intracellular signaling. Specific targets of interest are the mitogen-activated protein kinase phosphatases (MKPs), cellular enzymes involved in cancer, inflammation, and myocardial ischemia that have largely eluded discovery efforts. An important part of my research is the development of analysis tools to increase information content of biological assays and to enable small molecule drug discovery in whole multicellular organisms such as zebrafish. Kaltenmeier CT, Vollmer LL, Vernetti LA, Caprio L, Davis K, Korotchenko VN, Day BW, Tsang M, Hulkower KI, Lotze MT, Vogt A (2017) A tumor cell-selective inhibitor of mitogen-activated protein kinase phosphatases sensitizes breast cancer cells to lymphokine-activated killer cell activity. J Pharmacol Exp Ther. 361(1): 39-50 Colombo R, Wnag Z, Han J, Balachandran R, Daghestani HN, Camarco DP, Vogt A, Day BW, Mendel D, Wipf P (2016) Total Synthesis and Biological Evaluation of Tubulysin Analogs J Org Chem. 81(21): 10302-10320
	412-383-9146 vriesjk@pitt.edu Office: 3061 BST3 Lab Website	John K. Vries, MD - Associate Professor M.D., University of California San Francisco Asymmetry in the distribution of attributes along biological sequences generates signals with characteristic frequency and phase spectra. Asymmetry in the distribution of contacts in 3-dimensional models also generates signals with characteristic spectra. In some cases, these spectra are correlated. My research attempts to predict tertiary structure from these correlations. The long term goal is go develop an alignment-independent method for protein classification. The methodologies employed include n-gram analysis, Fourier analysis, eigenfunction decomposition and all poles spectral density estimation. In related research, correlations between the periodicity of pairwise relationships in molecular dynamics simulations and the results of Gaussian network analysis are compared. Koes DR, Vries JK (2017) Evaluating Molecular Mechanics Force Fields with a Quantum Chemical Approach Biophysical Journal. 112 (3): 289a Koes DR, Vries JK (2017) Error assessment in molecular dynamics trajectories using computed NMR chemical shifts Computational and Theoretical Chemistry. 1099: 152-166
	412-383-5743 xing1@pitt.edu Office: 3084 BST3 Lab Website	Jianhua Xing, PhD - Associate Professor Ph.D., Theoretical Chemistry, University of California, Berkeley, 2002 The Xing lab is interested in the following fundamental questions. How do thousands of molecules species orchestrate temporally and spatially to determine a cell phenotype? How can one regulate and direct cell phenotype? Specifically, the lab currently focuses on Epithelial-to-Mesenchymal Transition (EMT), characterized by loss of cell-cell adhesion and increased cell motility. EMT plays important roles in embryonic development, tissue regeneration, wound healing and pathological processes such as fibrosis in lung, liver, and kidney, and cancer metastasis. The lab studies the coupled gene expression and epigenetic dynamics of EMT. Zhang H, Tian X, Kim KS, Xing JH (2014) Statistical mechanics model for the dynamics of collective epigenetic histone modification, Physical Review Letters. 112: 068101 Wang P, Song C, Zhang H, Wu Z, Tian XJ, Xing JH (2014) Epigenetic state network approach for describing cell phenotypic transitions Interface Focus. 4(3): 20130068
Emeritus Faculty
	412-648-3333 hagaim@pitt.edu Lab Website	Hagai Meirovitch, PhD - Professor Emeritus Ph.D. in Statistical Mechanics, The Weizmann Institute of Science Structure and function of proteins by the energetic and statistical approaches. Development of modeling of solvation, methods for calculating the entropy and the free energy of macromolecules and fluids (water), and simulation and conformational search techniques for protein systems. These methods are components of a new statistical mechanics methodology for treating flexibility applied to loops, peptides, and active sites to understand protein-protein and protein-ligand recognition processes (e.g., antibody-antigen interactions) and to analyze NMR and x-ray data of flexible molecules. General IJ, Dragomirova R, Meirovitch H (2012) Absolute free energy of binding of avidin/biotin, revisited J Phys Chem B. 116: 6628-36 Meirovitch H (2010) Methods for calculating the absolute entropy and free energy of biological systems based on ideas from polymer physics. J Mol Recognit. 23: 153-72