Jinhua Wu, PhD
- PhD, Structural Biology, Purdue University, West Lafayette, IN, 2004
- BS, Biology, University of Science and Technology of China, Hefei, China, 1997
- Health Research Formula Grant Award, Pennsylvania Department of Health 2015
- Member, American Cancer Society 2014
- American Cancer Society Institutional Research Grant Pilot Project Award 2012
- Member, Fox Chase Cancer Center Cell Signaling Group 2010
- Member, Fox Chase Cancer Center Head and Neck Keystone 2010
- Member, Fox Chase Cancer Center Molecular Modeling Facility Advisory Committee 2010
- Member, Sigma Xi Scientific Research Society 2007 - 2008
- Member, American Association for the Advancement of Science 2007 - 2008
- Member, New York Structural Biology Discussion Group 2005
- Member, American Cyrstallographic Association 2001 - 2007
Structural and Functional studies of integrin signaling
- Structural basis to the regulatory mechanisms of the inside-out integrin signaling.
- Structural and functional analyses of the MRL family proteins.
- Development of anti-talin inhibitors by structure-based computer-aided design.
Alterations in the regulation or expression of integrins have been implicated in many human diseases including inflammatory disorders, cardiovascular diseases, and cancer. In cancer biology, altered expression of integrins has been linked to tumor cell proliferation, metastasis and survival due to their role as adhesion receptors. Hence the integrin signaling pathway has become an appealing target for cancer therapy. Integrins can be activated by extracellular ligand binding in an outside-in manner or by growth factor stimulation through an inside-out pathway. Although antagonistic inhibitors have been shown to reduce early tumor angiogenesis, the inconsistent effect remain major obstacles for anti-cancer drug development. Alternatively, Integrin activities may also be suppressed by blocking the specific interactions of intracellular elements in the inside-out signaling.
The main focus of my lab is to understand the structural basis of intermolecular complexes and intramolecular rearrangements that control integrin-mediated cell adhesion and motility. Understanding the structural details of each signaling event, particularly the protein-protein interactions involved in this pathway, is the key to developing next-generation inhibitors. We aim to elucidate the structural basis of cytosolic inter-molecular complexes and intra-molecular domain rearrangements that modify the integrin activation, to validate these specific interactions revealed in the crystal structures, and to assess their roles in integrin activation in biochemical and physiological contexts. Our lab employes a combination of X-ray crystallography, biochemical and biophysical assays, cell-based functional studies, computer modeling, and organic synthesis to accomplish these goals.
Zhang H, Chang YC, Huang Q, Brennan ML, Wu J. Structural and Functional Analysis of a Talin Triple-Domain Module Suggests an Alternative Talin Autoinhibitory Configuration Structure. 2016 24(5):721-9. PubMed
Yang J, Zhu L, Zhang H, Hirbawi J, Fukuda K, Dwivedi P, Liu J, Byzova T, Plow EF, Wu J**, Qin J**. Conformational activation of talin by RIAM triggers integrin-mediated cell adhesion. Nat Comm Epub 2014 Dec 18. PubMed
Chang YC, Zhang H, Brennan ML, Franco-Barraza J, Patel T, Cukierman E, Wu J. Structural and mechanistic insights into the recruitment of talin by RIAM in integrin signaling. Structure 2014 22(12):1810-20. PubMed
Zhang H, Chang YC, Brennan ML, Wu J. The structure of Rap1 in complex with RIAM reveals specificity determinants and recruitment mechanism. J Mol Cell Biol 2014 6(2):128-39. PubMed
Anastassiadis T, Duong-Ly KC, Deacon SW, Lafontant A, Ma H, Devarajan K, Dunbrack RL Jr, Wu J, Peterson JR. A highly selective dual insulin receptor (IR)/insulin-like growth factor 1 receptor (IGF-1R) inhibitor derived from an extracellular signal-regulated kinase (ERK) inhibitor. J Biol Chem. 2013 Sep 27;288(39):28068-77. doi: 10.1074/jbc.M113.505032. Epub 2013 Aug 9. PubMed
Chang YC, Zhang H, Brennan ML, Wu J. Crystal structure of Lamellipodin implicates diverse functions in actin polymerization and Ras signaling. Protein Cell. 2013 Mar;4(3):211-9. doi: 10.1007/s13238-013-2082-5. Epub 2013 Mar 13. PubMed
Wynne JP*, Wu J*, Su W, Mor A, Patsoukis N, Boussiotis VA, Hubbard SR, Philips MR. Rap1-interacting adapter molecule (RIAM) associates with the plasma membrane via a proximity detector. J Cell Biol. 2012 Oct 15;199(2):317-30. doi: 10.1083/jcb.201201157. Epub 2012 Oct 8. *Equal contribution. PubMed
Ungureanu D, Wu J, Pekkala T, Niranjan Y, Young C, Jensen ON, Xu CF, Neubert TA, Skoda RC, Hubbard SR, Silvennoinen O. The pseudokinase domain of JAK2 is a dual-specificity protein kinase that negatively regulates cytokine signaling. Nat Struct Mol Biol. 2011 Aug 14. [Epub ahead of print] PubMed
Depetris RS*, Wu J*, Hubbard, S.R. Structural and functional studies of the Ras-associating and pleckstrin-homology domains of Grb10 and Grb14. Nat Struct Mol Biol. 2009;16,833-9. *Equal contribution. PubMed
Wu J*, Li W*, Craddock BP, Foreman KW, Mulvihill MJ, Ji QS, Miller WT, Hubbard SR. Small-molecule inhibition and activation-loop trans-phosphorylation of the IGF1 receptor. EMBO J. 2008;27,1985-94. *Equal contribution. PubMed
Wu J, Tseng Y, Xu C, Neubert TA, White MF, and Hubbard SR. Structural and biochemical characterization of the KRLB region in insulin receptor substrate-2. Nat Struct Mol Biol. 2008;15,251-8. PubMed