Qiang Zhang, M.D., Ph.D.
Research Investigator and Director, Center for Dose Response Modeling
M.D., Harbin Medical University, People's Republic of China, 1995.
Ph.D., physiology and neurobiology, University of Connecticut, 2003.
Postdoctoral training, Division of Computational Biology, CIIT Centers for Health Research, Research Triangle Park, North Carolina, 2003-2006.
My research interest is focused on understanding how molecular circuits operating in cells mediate cellular responses to external perturbations, such as by environmental chemical toxicants, and how the altered dynamics of these circuits underlie various nonlinear dose response behaviors for multiple biological and toxicological endpoints. In close collaboration with experimental biologists, I use mathematical modeling approaches to study several cellular response pathways. One is the adaptive response pathways handling cellular stress and maintaining homeostasis. Time series and steady-state responses are investigated both computationally and experimentally with focuses on the antioxidant response and p53 DNA damage response pathways. The role of negative feedback circuitry in these pathways is extensively studies for the origin of nonlinear response. Another research area I am interested in is to understand the molecular circuitry underlying all-or-none type of cellular responses, as occurring during cell differentiation, cell proliferation and apoptosis. Research in this area has focused on the terminal differentiation of B cells in response to antigens and how the environmental pollutant dioxin interferes with this process. Recently efforts have also been devoted to modeling the mammalian cell cycle and understanding the effect of chemicals on proliferation rate.
The emerging field of computational systems biology – a novel discipline to study cells from a dynamical system perspective – has brought new challenges to biologists and toxicologists who traditionally study biological systems in a descriptive rather than quantitative way. To accelerate the transformation of toxicological science, disseminating the new tools of dose response modeling and quantitative risk assessment is essential. With colleagues at the Hamner Institutes, I have organized several training workshops and short courses to practicing toxicologists, risk assessment professionals, and graduate students. With extensive hands-on computer exercises, these trainings teach essential concepts and principles in quantitative cell biology and the network motif mechanisms for nonlinear dose responses. Some of the Dose Response Modeling workshops we offered can be found on the website under Education and Training
Selected Publications - click to view
Hou Y., Xue P., Bai Y., Liu D., Woods C.G., Yarborough K., Fu J., Zhang Q., Sun G., Collins S., Chan J.Y., Yamamoto M., Andersen M.E., Pi J. (2012). Nuclear Factor Erythroid-Derived Factor 2-Related Factor 2 Regulates Transcription of CCAAT/Enhancer-Binding Protein β during Adipogenesis. Free Radic Biol Med. 52(2):462-72.
Bhattacharya S., Zhang Q., and Andersen M.E. (2011). A deterministic Map of Waddington's Epigenetic Landscape for Cell Fate Specification. BMC Systems Biology. 5:85.
Bhattacharya S., Zhang Q., Carmichael P.L., Boekelheide K., and Andersen M.E. (2011). Toxicity Testing In the 21st Century: Defining New Risk Assessment Approaches Based on Perturbation of Intracellular Toxicity Pathways. PLoS ONE. 6(6): e20887.
Bhattacharya S., Zhang Q., and Andersen M.E. (2011). Double-negative feedback loops as a common design motif in the transcriptional networks regulating cell fate. International Journal of Design Engineering. 4(1): 41-57.
Xue P., Hou Y., Zhang Q., Woods C.G., Yarborough K., Liu H., Sun G., Andersen M.E., and Pi J. (2011). Prolonged Inorganic Arsenite Exposure Suppresses Insulin-Stimulated AKT S473 Phosphorylation and Glucose Uptake in 3T3-L1 Adipocytes: Involvement of the Adaptive Antioxidant Response. Biochem Biophys Res Commun. 407(2): 360-365.
Zhang Q., Bhattacharya S., Andersen M.E., and Conolly R.B. (2010). Computational Systems Biology and Dose Response Modeling in Relation to New Directions in Toxicity Testing. Journal of Toxicology and Environmental Health Part B. 13(2): 253-276.
Fu J., Woods C.G., Yehuda-Shnaidman E., Zhang Q., Wong V., Collins S., Sun G., Andersen M.E., and Pi J. (2010). Low Levels of Arsenic Impair Glucose-Stimulated Insulin Secretion in Pancreatic Beta-Cells: Involvement of Cellular Adaptive Response to Oxidative Stress. Environmental Health Perspective. 118(6): 864-870.
Bhattacharya S., Conolly R.B., Kaminski N.E., Thomas R.S., Andersen M.E., and Zhang Q. (2010). A Bistable Switch Underlying B-Cell Differentiation and Its Disruption by the Environmental Contaminant 2,3,7,8-Tetrachlorodibenzo-p-dioxin. Toxicological Sciences. 115(1), 51–65.
Zhang Q., Bhattacharya S., Crawford R.B., Kline D.E., Thomas R.S., Conolly R.B., Kaminski N.E., and Andersen M.E. (2010). Stochastic Modeling of B Cell Terminal Differentiation and Its Repression by Dioxin. BMC Systems Biology. 4:40.
Zhang Q., Pi J., Woods C.G., and Andersen M.E. (2010). A Systems Biology Perspective on Nrf2-mediated Antioxidant Response. Toxicology and Applied Pharmacology. 244(1): 84-97.
Pi J., Zhang Q., Fu J., Woods C.G., Hou Y., Collins S., Andersen M.E. (2010). ROS Signaling, Oxidative Stress and Nrf2 in Pancreatic β-cell Function. Toxicology and Applied Pharmacology. 244(1): 77-83.
Woods C.G., Fu J., Zhang Q., Yang L., Thomas R.S., Andersen M.E., Pi J. (2009). Dose-Dependent Transitions in Nrf2-Mediated Adaptive Response and Related Stress Responses to Hypochlorous Acid in Mouse Macrophages. Toxicology and Applied Pharmacology. 238(1): 27-36.
Zhang Q., Pi J., Woods C.G., and Andersen M.E. (2009). Phase I to II Cross-Induction of Xenobiotic Metabolizing Enzymes: a Feedforward Control Mechanism for Potential Hormetic Responses. Toxicology and Applied Pharmacology. 237(3): 345-356.
Zhang Q., Pi J., Woods C.G., Jarabek A.M., Clewell H.J. III, and Andersen M.E. (2008). Hormesis and Adaptive Cellular Control Systems. Dose-Response. 6(2):196-208.
Pi J., Zhang Q., Woods C.G., Wong V., Collins S., and Andersen M.E. (2008). Activation of Nrf2-Mediated Oxidative Stress Response in Macrophages by Hypochlorous Acid. Toxicology and Applied Pharmacology. 226(3): 236-243.
Li L., Heber S., Andersen M.E., and Zhang Q. (2007). Non-Monotonic Dose Response Relationship in Steroid Hormone Receptor-mediated Gene Expression. Journal of Molecular Endocrinology. 38(5): 569–585.
Pi J., Bai Y., Zhang Q., Wong V., Floering L.M., Daniel K., Reece J.M., Deeney J.T., Andersen M.E., Corkey B.E., and Collins S. (2007). Reactive Oxygen Species as a Signal in Glucose-stimulated Insulin Secretion. Diabetes. 56(7): 1783-1791.
Zhang Q. and Andersen M.E. (2007). Dose Response Relationship in Anti-Stress Gene Regulatory Networks. PLoS Comput Biol. 3(3): e24.
Zhang Q., Andersen M.E., and Conolly R.B. (2006). Binary Gene Induction and Protein Expression in Individual Cells. Theor Biol Med Model. 3(1): 18.
Zhang Q. and Gallo R.V. (2003). Presence of Kappa-opioid Tone at the Onset of the Ovulatory Luteinizing Hormone Surge in the Proestrous Rat. Brain Res. 980, 135-139.
Zhang Q., McCoy J.M., and Gallo R.V. (2002). Further Studies on Possible Dynorphin Involvement in the Ovulatory Luteinizing Hormone Surge in the Proestrous Rat. Endocrine. 18, 231-238.
Zhang Q. and Gallo R.V. (2002). The Effect of Prodynorphin-derived Opioid Peptides on the Ovulatory Luteinizing Hormone Surge in the Proestrous Rat. Endocrine. 18, 27-32.
- Melvin E. Andersen, Ph.D., DABT, CIH
- Sudin Bhattacharya, Ph.D.
- Jerry Campbell, Jr., Ph.D.
- Kyoungju Choi, Ph.D.
- Rebecca A. Clewell, Ph.D.
- Harvey J. Clewell III, Ph.D., DABT
- Darol E. Dodd, Ph.D., DABT
- Joshua A. Harrill, Ph.D.
- Alison H. Harrill, Ph.D.
- Brett A. Howell, Ph.D.
- Edward L. LeCluyse, Ph.D.
- Jingbo Pi, M.D., Ph.D.
- Russell S. Thomas, Ph.D.
- Paul B. Watkins, M.D.
- Barbara A. Wetmore, Ph.D.
- Yuching Yang, Ph.D.
- Miyoung Yoon, Ph.D.
- Qiang Zhang, M.D., Ph.D.