Professor of Pharmacology
Ph.D. - University of Chicago
Key Words: Spatiotemporal regulation of signal transduction
Our ultimate goal is to understand how cells, the basic units of life, sense changing environments and orchestrate specific responses to carry out life processes. Recent years have seen tremendous progress in identifying molecular components constituting a signaling network that control various life processes. Less well developed is our understanding of how these components are precisely regulated to achieve signaling specificity within a living cell, which may be reacting to multiple inputs simultaneously. The key is believed to lie in the spatiotemporal information encoded in a particular cellular context.
We are investigating the molecular mechanisms and functional roles of such spatiotemporal regulation by taking a "native biochemistry" approach. With the help of a series of new molecular tools and the state-of-art imaging technology, we study the properties and action of protein kinases and second messengers in living biological systems. Current projects include engineering novel fluorescent biosensors to track the activities of second messengers, kinases and phosphatases and investigating the spatiotemporal regulation of cAMP/PKA, Ca2+/calcineurin, PI3K/Akt/mTOR, MAPK and AMPK pathways, in the context of energy metabolism, cell differentiation or insulin secretion by β cells. Quantitative measurement from live-cell fluorescence imaging is combined with mechanistic computational modeling for systems analyses of signaling networks.
Sample V, Ramamurthy S, Gorshkova K, Ronnett GV and Zhang J. Polarized activities of AMPK and BRSK in primary hippocampal neurons. Mol Biol Cell, 2015, in press.
Zhou X, Clister TL, Lowry PR, Seldin MM, Wong GW and Zhang J. Dynamic Visualization of mTORC1 Activity in Living Cells. Cell Rep. 2015, pii: S2211-1247(15)00177-1, in press.
Mehta S, Aye-Han N, Ganesan A, Oldach L, Gorshkov K, and Zhang J. Calmodulin-controlled Spatial Decoding of Oscillatory Ca2+ Signals by Calcineurin. eLife, 2014, e03765.
Newman RE*, Hu J*, Rho H*, Xie Z*, Woodard C, Neiswinger J, Hwang W, Shirley M, Hu S, Cooper C, Jeong JS, Wu G, Lin J, Gao X, Ni Q, Ji H, Desiderio S, Dalby KN, Birnbaum MJ, Cole PA, Knapp S, Ryazanov A, Zack DJ, Blackshaw S, Pawson T, Gingras A, Pandey A, Turk BE, Zhang J+, Zhu H+, Qian J+. Construction of human activity-based phosphorylation networks. *Equal contribution. +Co-corresponding authors. Mol. Syst. Biol. 2013; 9:655.
Dedecker P+, Mo GCH, Dertinger T, and Zhang J+. Widely accessible method for superresolution fluorescence imaging of living systems. +Co-corresponding authors. Proc. Natl. Acad. Sci. USA 2012; 109(27): 10909-14.