Jinhua Wu, PhD

Jinhua Wu, PhD

Assistant Professor

Research Program

Fig. 1
Figure 1. Molecular Mechanisms of the Inside-out Integrin Signaling Pathway
Fig. 2
Figure 2. Molecular mechanisms governing activation of integrin by MRL proteins
Fig. 3
Figure 3. Interaction of TBS1 with talin rod region. A. Crystal structure of talin R7R8 in complex with RIAM TBS1 peptide. TBS1-interacting helices in R8 are 2 and 3. Hydrogen bond network mediated Ser13 is shown in the close-in view. B. Hydrophobic interactions are represented by a light gray surface with residues of TBS1 in blue stroke and residues of R8 in yellow stroke. C. Hydrogen bonds are denoted by a dotted line.
Fig. 4
Figure 4. (Left) CHO cells stably expression integrin alphaIIb/beta3 were transiently transfected with mCherry-talin and GFP-RIAM-TBS1-CAAX and its mutants. The cells were plated on fibrinogen-coated coverslips and allowed to adhere and spread. Yellow colors in merged images represent areas of common red and green localizations. (Right) Enlarged lamellae sections correspond to the white rectangles marked in the left. Note that small histogram graphs are representative of intensity levels of the assorted overexpressed proteins. While WT RIAM-TBS1 and talin colocalized at the lamellae, the mutants failed to recruit talin into the lamellae.
Fig. 5
Figure 5. Interaction of TBS1 with talin head region. A. NMR structure of talin F3 domain in complex with the RIAM TBS1 peptide. The side chains of the residues involved in the interaction are labeled. B. The structure of talin-F3 (blue) bound to RIAM-TBS1 (salmon) was superimposed onto the talin-F3 (green) bound to talin-R9 (gray). TBS1 sterically interferes with the autoinhibitory interface of F3:R9. C. Superposition of TBS1 bound talin-F3 with integrin- (yellow) bound talin-F3 indicates that TBS1 binds to a neighboring region of the integrin-binding site on talin-F3. D. Superposition of the TBS1 fragments in complex with R8 of talin-R (purple:green) or with F3 of talin-H (salmon:blue).
Education, Training & Credentials

Educational Background

  • 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
Research Profile

Research Program

Research Interests

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.

Lab Overview

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.


Yu-Chung Chang, PhD

Postdoctoral Associate

Room: W410

Hao Zhang, PhD

Research Associate

Room: W410

Rebecca Stronk, BS

Scientific Technician

Room: W410

Selected Publications

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

Additional Publications


This Fox Chase professor participates in the Undergraduate Summer Research Fellowship
Or learn more about Research Volunteering.