Jin Zhang, Ph.D.
Vice Chair and Professor of Pharmacology
Research Interests
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. The past decades have seen tremendous progress in identifying the molecular components that constitute the structural, biochemical and mechanical networks that control various life processes. Less well developed is our understanding of how these components are precisely regulated to achieve the functional specificity within a living cell, which may be simultaneously reacting to multiple inputs from the changing environment. It has been increasingly clear that the key lies 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. This allows us to unravel chemical mechanisms of life processes in the framework of cellular time and space, where molecular changes can be directly linked to functional effects. Combing genetically encoded fluorescent biosensors, superresolution imaging, targeted biochemical perturbations and mathematic modeling, the Zhang laboratory is investigating the spatiotemporal regulation of GPCR, cAMP/PKA, Ca2+/calcineurin, PI3K/Akt/mTOR, Ras/ERK and AMPK pathways, in the context of energy metabolism, neuronal activity, cardiovascular homeostasis, insulin secretion by β cells as well as tumorigenesis.
Selected Publications
Hardy JC, Pool EH, Bruystens JGH, Zhou X, Li Q, Zhou DR, Palay M, Tan G, Chen L, Choi JLC, Lee HN, Strack S, Wang D, Taylor SS, Mehta S, and Zhang J. Molecular Determinants and Signaling Effects of PKA RIα Phase Separation. Mol Cell, 2024, 84(8):1570-1584.
Frei M, Mehta S and Zhang J. Next-Generation Genetically Encoded Fluorescent Biosensors Illuminate Cell Signaling and Metabolism. Rev. Biophys. 2024 doi: 10.1146/annurev-biophys-030722-021359
Kwon Y, Mehta S, Clark M, Walters G, Zhong Y, Lee HN, Sunahara RK, and Zhang J. Non-canonical β-adrenergic activation of ERK at endosomes. Nature. 2022, 611(7934): 173-179.
Zhang JF*, Liu B*, Hong I*, Mo A, Roth RH, Tenner B, Lin W, Zhang JZ, Molina RS, Drobizhev M, Hughes TE, Tian L, Huganir RH†, Mehta S†, and Zhang J†. An ultrasensitive biosensor for high-resolution kinase activity imaging in awake mice. Chem. Biol. 2021, 17(1): 39-46.
Zhou X, Zhong Y, Molinar-Inglis O, Kunkel MT, Chen M, Sun T, Zhang J, Shyy JY, Trejo J, Newton AC, and Zhang J., Location-specific inhibition of Akt reveals regulation of mTORC1 activity in the nucleus. Nat Commun. 2020, 11(1):6088.
Zhang JZ, Lu TW, Stolerman LM, Tenner B, Yang J, Zhang JF, Falcke M, Rangamani P, Taylor SS, Mehta S, Zhang J. Phase separation of a regulatory subunit of Protein Kinase A controls cAMP compartmentation and oncogenic signaling, Cell, 2020, 182(6):1531-1544.