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Dr. Jin Zhang

Ph.D.
Titles

Associate Professor of Pharmacology and Molecular Sciences
Assistant Professor of Oncology
Assistant Professor of Neuroscience

Schools\Degrees

Ph.D., University of Chicago

Training

The University of California, San Diego

Research Summary

Dr. Zhang’s research involves an interdisciplinary approach using a combination of live-cell imaging, protein engineering and chemical and cellular biology to elucidate the dynamic modulation and compartmentation of kinases and second messengers and their functional roles in regulating chemotaxis, adipocyte physiology, and cancer development.

Cell Signaling; Kinases and Phosphatases; Chemotaxis; Live-cell Imaging; Fluorescent Proteins and Reporters; Chemical BiologyAll living cells monitor their surroundings and interpret various environmental cues in order to respond appropriately to changing conditions. Signal transduction is the mechanism by which cellular information is processed and signal inputs are converted to specific pathway outputs. Despite the great diversity of information processed and the numerous signaling components involved, it is likely that only a limited number of fundamental strategies are used for signal transduction. One such strategy is to achieve specificity in signal transduction by temporal coordination and spatial compartmentation of signaling components. For example, compartmentation of kinases, phosphatases, and substrates is widely conjectured to be a key determinant in the specificity of various signaling pathways. We are interested in understanding the molecular basis and cellular consequences of such spatiotemporal regulation.

Our approach is to design, synthesize, and apply molecular tools that allow us to monitor and perturb signaling processes with precise spatial and temporal control. To monitor signaling processes, we will employ fluorescent protein-based indicators that can be designed to respond to a variety of biological events and signals and used for visualization and tracking of various cellular events in real time and space. Perturbation strategies, such as photochemical manipulation, small-molecule modulation, and RNA interference, are powerful techniques for dissecting signaling pathways and provide various degrees of spatiotemporal control. Using a combination of live-cell imaging, protein engineering and evolution, chemical biology, and molecular cell biology, our interdisciplinary research effort will involve developing imaging probes and perturbation tools for use in living mammalian cells. These new tools will be applied to the study of dynamic modulation and compartmentation of kinase activities in the context of the molecular mechanisms regulating cell polarity in cell migration and chemotaxis.

Journal Citations

Allen, M.D.; DiPilato, L.M.; Rahdar, M.; Ren, Y.R.; Chong, C.; Liu, J.O.; Zhang, J. Reading dynamic kinase activity in living cells for high-throughput screening. ACS chemical biology. 2006 Jul 21;1(6):371-376.

Allen, M.D.; Zhang, J. Subcellular dynamics of protein kinase A activity visualized by FRET-based reporters. Biochem Biophys Res Commun. 2006 Sep 22;348(2):716-721.

Shamay, M.; Krithivas, A.; Zhang, J.; Hayward, S.D. Recruitment of the de novo DNA methyltransferase Dnmt3a by Kaposi's sarcoma-associated herpesvirus LANA. Proc Natl Acad Sci U S A. 2006 Sep 26;103(39):14554-14559.

Chen, L.; Zhang, Z.; Chen, W.; Zhang, Z.; Li, Y.; Shi, M.; Zhang, J.; Chen, L.; Wang, S.; Wang, F.S. B7-H1 up-regulation on myeloid dendritic cells significantly suppresses T cell immune function in patients with chronic hepatitis B. J Immunol. 2007 May 15;178(10):6634-6641.

Zhang, J.; van Zijl, P.C.; Laterra, J.; Salhotra, A.; Lal, B.; Mori, S.; Zhou, J. Unique patterns of diffusion directionality in rat brain tumors revealed by high-resolution diffusion tensor MRI. Magnetic resonance in medicine : official journal of the Society of Magnetic Resonance in Medicine / Society of Magnetic Resonance in Medicine. 2007 Sep;58(3):454-462.

Hua, K.; Oishi, K.; Zhang, J.; Wakana, S.; Yoshioka, T.; Zhang, W.; Akhter, K.D.; Li, X.; Huang, H.; Jiang, H.; van Zijl, P.; Mori, S. Mapping of Functional Areas in the Human Cortex Based on Connectivity through Association Fibers. Cerebral cortex (New York, NY: 1991). 2008 Dec 9;19:1889-1895.

Ren, Y.R.; Pan, F.; Parvez, S.; Fleig, A.; Chong, C.R.; Xu, J.; Dang, Y.; Zhang, J.; Jiang, H.; Penner, R.; Liu, J.O. Clofazimine inhibits human Kv1.3 potassium channel by perturbing calcium oscillation in T lymphocytes. PLoS ONE. 2008;3(12):e4009.

Stone, B.S.; Zhang, J.; Mack, D.W.; Mori, S.; Martin, L.J.; Northington, F.J. Delayed neural network degeneration after neonatal hypoxia-ischemia. Annals of Neurology. 2008 Nov;64(5):535-546.

Szewczuk, L.M.; Tarrant, M.K.; Sample, V.; Drury, W.J., 3rd; Zhang, J.; Cole, P.A. Analysis of serotonin N-acetyltransferase regulation in vitro and in live cells using protein semisynthesis. Biochemistry. 2008 Sep 30;47(39):10407-10419.

Lin, Y.Y.; Lu, J.Y.; Zhang, J.; Walter, W.; Dang, W.; Wan, J.; Tao, S.C.; Qian, J.; Zhao, Y.; Boeke, J.D.; Berger, S.L.; Zhu, H. Protein acetylation microarray reveals that NuA4 controls key metabolic target regulating gluconeogenesis. Cell. 2009 Mar 20;136(6):1073-1084.

Mullighan, C.G.; Su, X.; Zhang, J.; Radtke, I.; Phillips, L.A.; Miller, C.B.; Ma, J.; Liu, W.; Cheng, C.; Schulman, B.A.; Harvey, R.C.; Chen, I.M.; Clifford, R.J.; Carroll, W.L.; Reaman, G.; Bowman, W.P.; Devidas, M.; Gerhard, D.S.; Yang, W.; Relling, M.V.; Shurtleff, S.A.; Campana, D.; Borowitz, M.J.; Pui, C.H.; Smith, M.; Hunger, S.P.; Willman, C.L.; Downing, J.R. Deletion of IKZF1 and Prognosis in Acute Lymphoblastic Leukemia. N Engl J Med. 2009 Jan 7;360:470-480.

Zhang, J.; Johnson, P.C.; Popel, A.S. Effects of erythrocyte deformability and aggregation on the cell free layer and apparent viscosity of microscopic blood flows. Microvasc Res. 2009 May;77(3):265-272.

Zhang, J.; Sprung, R.; Pei, J.; Tan, X.; Kim, S.; Zhu, H.; Liu, C.F.; Grishin, N.V.; Zhao, Y. Lysine acetylation is a highly abundant and evolutionarily conserved modification in Escherichia coli. Mol Cell Proteomics. 2009 Feb;8(2):215-225.

Zhang, W.; Li, X.; Zhang, J.; Luft, A.; Hanley, D.F.; van Zijl, P.; Miller, M.I.; Younes, L.; Mori, S. Landmark-referenced voxel-based analysis of diffusion tensor images of the brainstem white matter tracts: application in patients with middle cerebral artery stroke. NeuroImage. 2009 Feb 1;44(3):906-913.

Zhu, J.; Liao, G.; Shan, L.; Zhang, J.; Chen, M.R.; Hayward, G.S.; Hayward, S.D.; Desai, P.; Zhu, H. Protein array identification of substrates of the Epstein-Barr virus protein kinase BGLF4. J Virol. 2009 May;83(10):5219-5231.

Aggarwal, M.; Mori, S.; Shimogori, T.; Blackshaw, S.; Zhang, J. Three-dimensional diffusion tensor microimaging for anatomical characterization of the mouse brain. Magnetic resonance in medicine : official journal of the Society of Magnetic Resonance in Medicine / Society of Magnetic Resonance in Medicine. 2010;64(1):249-261.

Althoff, K.N.; Gange, S.J.; Klein, M.B.; Brooks, J.T.; Hogg, R.S.; Bosch, R.J.; Horberg, M.A.; Saag, M.S.; Kitahata, M.M.; Justice, A.C.; Gebo, K.A.; Eron, J.J.; Rourke, S.B.; Gill, M.J.; Rodriguez, B.; Sterling, T.R.; Calzavara, L.M.; Deeks, S.G.; Martin, J.N.; Rachlis, A.R.; Napravnik, S.; Jacobson, L.P.; Kirk, G.D.; Collier, A.C.; Benson, C.A.; Silverberg, M.J.; Kushel, M.; Goedert, J.J.; McKaig, R.G.; Van Rompaey, S.E.; Zhang, J.; Moore, R.D. Late presentation for human immunodeficiency virus care in the United States and Canada. Clin Infect Dis. 2010 Jun 1;50(11):1512-1520.

Depry, C.; Zhang, J. Visualization of kinase activity with FRET-based activity biosensors. Curr Protoc Mol Biol. 2010 Jul;Chapter 18:Unit 18 15.

Fan, X.; Khaki, L.; Zhu, T.S.; Soules, M.E.; Talsma, C.E.; Gul, N.; Koh, C.; Zhang, J.; Li, Y.M.; Maciaczyk, J.; Nikkhah, G.; Dimeco, F.; Piccirillo, S.; Vescovi, A.L.; Eberhart, C.G. NOTCH pathway blockade depletes CD133-positive glioblastoma cells and inhibits growth of tumor neurospheres and xenografts. Stem Cells. 2010 Jan;28(1):5-16.

Fosbrink, M.; Aye-Han, N.N.; Cheong, R.; Levchenko, A.; Zhang, J. Visualization of JNK activity dynamics with a genetically encoded fluorescent biosensor. Proc Natl Acad Sci U S A. 2010 Mar 23;107(12):5459-5464.

Hector, A.; Montgomery, E.A.; Karikari, C.; Canto, M.; Dunbar, K.B.; Wang, J.S.; Feldmann, G.; Hong, S.M.; Haffner, M.C.; Meeker, A.K.; Holland, S.J.; Yu, J.; Heckrodt, T.J.; Zhang, J.; Ding, P.; Goff, D.; Singh, R.; Roa, J.C.; Marimuthu, A.; Riggins, G.J.; Eshleman, J.R.; Nelkin, B.D.; Pandey, A.; Maitra, A. The Axl receptor tyrosine kinase is an adverse prognostic factor and a therapeutic target in esophageal adenocarcinoma. Cancer Biol Ther. 2010 Nov 29;10(10):1009-1018.

Hudson, T.J.; Anderson, W.; Artez, A.; Barker, A.D.; Bell, C.; Bernabe, R.R.; Bhan, M.K.; Calvo, F.; Eerola, I.; Gerhard, D.S.; Guttmacher, A.; Guyer, M.; Hemsley, F.M.; Jennings, J.L.; Kerr, D.; Klatt, P.; Kolar, P.; Kusada, J.; Lane, D.P.; Laplace, F.; Youyong, L.; Nettekoven, G.; Ozenberger, B.; Peterson, J.; Rao, T.S.; Remacle, J.; Schafer, A.J.; Shibata, T.; Stratton, M.R.; Vockley, J.G.; Watanabe, K.; Yang, H.; Yuen, M.M.; Knoppers, B.M.; Bobrow, M.; Cambon-Thomsen, A.; Dressler, L.G.; Dyke, S.O.; Joly, Y.; Kato, K.; Kennedy, K.L.; Nicolas, P.; Parker, M.J.; Rial-Sebbag, E.; Romeo-Casabona, C.M.; Shaw, K.M.; Wallace, S.; Wiesner, G.L.; Zeps, N.; Lichter, P.; Biankin, A.V.; Chabannon, C.; Chin, L.; Clement, B.; de Alava, E.; Degos, F.; Ferguson, M.L.; Geary, P.; Hayes, D.N.; Johns, A.L.; Kasprzyk, A.; Nakagawa, H.; Penny, R.; Piris, M.A.; Sarin, R.; Scarpa, A.; van de Vijver, M.; Futreal, P.A.; Aburatani, H.; Bayes, M.; Botwell, D.D.; Campbell, P.J.; Estivill, X.; Grimmond, S.M.; Gut, I.; Hirst, M.; Lopez-Otin, C.; Majumder, P.; Marra, M.; McPherson, J.D.; Ning, Z.; Puente, X.S.; Ruan, Y.; Stunnenberg, H.G.; Swerdlow, H.; Velculescu, V.E.; Wilson, R.K.; Xue, H.H.; Yang, L.; Spellman, P.T.; Bader, G.D.; Boutros, P.C.; Flicek, P.; Getz, G.; Guigo, R.; Guo, G.; Haussler, D.; Heath, S.; Hubbard, T.J.; Jiang, T.; Jones, S.M.; Li, Q.; Lopez-Bigas, N.; Luo, R.; Muthuswamy, L.; Ouellette, B.F.; Pearson, J.V.; Quesada, V.; Raphael, B.J.; Sander, C.; Speed, T.P.; Stein, L.D.; Stuart, J.M.; Teague, J.W.; Totoki, Y.; Tsunoda, T.; Valencia, A.; Wheeler, D.A.; Wu, H.; Zhao, S.; Zhou, G.; Lathrop, M.; Thomas, G.; Yoshida, T.; Axton, M.; Gunter, C.; Miller, L.J.; Zhang, J.; Haider, S.A.; Wang, J.; Yung, C.K.; Cross, A.; Liang, Y.; Gnaneshan, S.; Guberman, J.; Hsu, J.; Chalmers, D.R.; Hasel, K.W.; Kaan, T.S.; Lowrance, W.W.; Masui, T.; Rodriguez, L.L.; Vergely, C.; Bowtell, D.D.; Cloonan, N.; deFazio, A.; Eshleman, J.R.; Etemadmoghadam, D.; Gardiner, B.A.; Kench, J.G.; Sutherland, R.L.; Tempero, M.A.; Waddell, N.J.; Wilson, P.J.; Gallinger, S.; Tsao, M.S.; Shaw, P.A.; Petersen, G.M.; Mukhopadhyay, D.; DePinho, R.A.; Thayer, S.; Shazand, K.; Beck, T.; Sam, M.; Timms, L.; Ballin, V.; Lu, Y.; Ji, J.; Zhang, X.; Chen, F.; Hu, X.; Yang, Q.; Tian, G.; Zhang, L.; Xing, X.; Li, X.; Zhu, Z.; Yu, Y.; Yu, J.; Tost, J.; Brennan, P.; Holcatova, I.; Zaridze, D.; Brazma, A.; Egevard, L.; Prokhortchouk, E.; Banks, R.E.; Uhlen, M.; Viksna, J.; Ponten, F.; Skryabin, K.; Birney, E.; Borg, A.; Borresen-Dale, A.L.; Caldas, C.; Foekens, J.A.; Martin, S.; Reis-Filho, J.S.; Richardson, A.L.; Sotiriou, C.; Thoms, G.; van't Veer, L.; Birnbaum, D.; Blanche, H.; Boucher, P.; Boyault, S.; Masson-Jacquemier, J.D.; Pauporte, I.; Pivot, X.; Vincent-Salomon, A.; Tabone, E.; Theillet, C.; Treilleux, I.; Bioulac-Sage, P.; Decaens, T.; Franco, D.; Gut, M.; Samuel, D.; Zucman-Rossi, J.; Eils, R.; Brors, B.; Korbel, J.O.; Korshunov, A.; Landgraf, P.; Lehrach, H.; Pfister, S.; Radlwimmer, B.; Reifenberger, G.; Taylor, M.D.; von Kalle, C.; Majumder, P.P.; Pederzoli, P.; Lawlor, R.A.; Delledonne, M.; Bardelli, A.; Gress, T.; Klimstra, D.; Zamboni, G.; Nakamura, Y.; Miyano, S.; Fujimoto, A.; Campo, E.; de Sanjose, S.; Montserrat, E.; Gonzalez-Diaz, M.; Jares, P.; Himmelbaue, H.; Bea, S.; Aparicio, S.; Easton, D.F.; Collins, F.S.; Compton, C.C.; Lander, E.S.; Burke, W.; Green, A.R.; Hamilton, S.R.; Kallioniemi, O.P.; Ley, T.J.; Liu, E.T.; Wainwright, B.J. International network of cancer genome projects. Nature. 2010 Apr 15;464(7291):993-998.

Li, X.; Klaus, J.A.; Zhang, J.; Xu, Z.; Kibler, K.K.; Andrabi, S.A.; Rao, K.; Yang, Z.J.; Dawson, T.M.; Dawson, V.L.; Koehler, R.C. Contributions of poly(ADP-ribose) polymerase-1 and -2 to nuclear translocation of apoptosis-inducing factor and injury from focal cerebral ischemia. J Neurochem. 2010 May;113(4):1012-1022.

Meguid, R.A.; Hooker, C.M.; Harris, J.; Xu, L.; Westra, W.H.; Sherwood, J.T.; Sussman, M.; Cattaneo, S.M., 2nd; Shin, J.; Cox, S.; Christensen, J.; Prints, Y.; Yuan, N.; Zhang, J.; Yang, S.C.; Brock, M.V. Long-term survival outcomes by smoking status in surgical and nonsurgical patients with non-small cell lung cancer: comparing never smokers and current smokers. Chest. 2010 Sep;138(3):500-509.

Ni, Q.; Zhang, J. Dynamic visualization of cellular signaling. Adv Biochem Eng Biotechnol. 2010;119:79-97.
Rojas, C.; Thomas, A.G.; Alt, J.; Stathis, M.; Zhang, J.; Rubenstein, E.B.; Sebastiani, S.; Cantoreggi, S.; Slusher, B.S. Palonosetron triggers 5-HT(3) receptor internalization and causes prolonged inhibition of receptor function. Eur J Pharmacol. 2010 Jan 25;626(2-3):193-199.

Bai, X.; Zhu, Y.; Jin, Y.; Guo, X.; Qian, G.; Chen, T.; Zhang, J.; Wang, J.; Groopman, J.D.; Gu, J.; Tu, H. Temporal acquisition of sequential mutations in the enhancer II and basal core promoter of HBV in individuals at high risk for hepatocellular carcinoma. Carcinogenesis. 2011 Jan;32(1):63-68.

Ni, Q.; Ganesan, A.; Aye-Han, N.N.; Gao, X.; Allen, M.D.; Levchenko, A.; Zhang, J. Signaling diversity of PKA achieved via a Ca2+-cAMP-PKA oscillatory circuit. Nat Chem Biol. 2011 Jan;7(1):34-40.

Shih, I.M.; Nakayama, K.; Wu, G.; Nakayama, N.; Zhang, J.; Wang, T.L. Amplification of the ch19p13.2 NACC1 locus in ovarian high-grade serous carcinoma. Mod Pathol. 2011 Jan 14;Epub 1/14/11.

 

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