Our lab is primarily focused on unraveling the mechanisms of receptor transmembrane signaling. Specifically, our attention is directed towards cell surface receptors featuring single transmembrane domains, such as integrins, receptor tyrosine kinases, and receptor-like tyrosine phosphatases. Through a multidisciplinary approach encompassing structural biology, protein engineering, biochemistry, and cell biology techniques, we aim to elucidate how these receptors transmit signals across the cell membrane. Our investigations center on understanding the conformational regulation triggered by ligand binding at the extracellular domain or cytoplasmic domain stimulations. Our goal is to illustrate the intricate mechanisms governing receptor-ligand interactions and the conformational changes necessary for transmembrane signaling, spanning the extracellular, transmembrane, and cytoplasmic domains.

We are currently engaged in several projects, delving into the conformational requirements for bi-directional transmembrane signaling in integrins, elucidating the structural and functional basis of integrins as pathogen receptors, exploring integrin ligand interactions, and developing antibodies and small molecules that target or stabilize specific integrin conformations. Integrins, crucial cell surface receptors, play a pivotal role in regulating cell-cell and cell-matrix interactions across various biological processes, including development, hemostasis, antigen recognition, homing, and inflammation. Dysregulation of integrin activation is observed in pathological conditions such as autoimmune diseases and thrombosis. Our overarching goal is to uncover the intricate correlation between receptor conformational regulation and signal transduction, aiming to contribute to the design of more efficient and safer therapeutic agents.

A new focus of our lab entails unraveling the mechanism behind coronavirus spike protein-mediated cell fusion and viral infection. We aim to apply the gained knowledge to develop inhibitors for antiviral treatment and diverse virus-based applications, including cell-specific gene delivery and oncolysis.

• NIH/NHLBI 5R01HL131836 “Structural transition of cellular integrins and applications thereof” Role: PI (2016-2024)
• NIH/NIGMS 1R01GM137143 Zhu “Structural Mechanisms Underlying the Activity Regulation of the Receptor-like Protein Tyrosine Phosphatase CD148/PTPRJ”
• NIH/NHLBI 1P01-HL167668 “Molecular mechanisms of immune thrombocytopenia in transfusion medicine” Role: Co-Investigator of Core A; PI of Core B; Co-Investigator of Projects 1 and 2.
• NIH/NIGMS 5R01GM137143 Zhu “Structural Mechanisms Underlying the Activity Regulation of the Receptor-like Protein Tyrosine Phosphatase CD148/PTPRJ” Role: PI

Huong (Helen) T.T. Nguyen, PhD
Heinrich Heine University Medical Center, Germany
Research Scientist I

Heng Zhang, PhD 
University of Waikato, New Zealand
Research Scientist I

Zhengli Wang, PhD
Ocean University of China, China
Research Scientist I

Lab Alumni

• Brandon Patterson, B.S., Graduate Student (MCW IDP) (2023)
• Liem Rao, Research Trainee (2023)
• Emily Zhang, Research Trainee (2023)
• Qifang Lao, M.D., Ph.D., Visiting Scholar (2021-2022)
• Kim Hung Huynh, Ph.D., Postdoctoral Fellow (2021-2022)
• Abigail Watson, B.S., Assistant Research Technologist (2021-2022)
• Cindy Nunez, B.S. Graduate Student (MCW IDP) (2021)
• Maya Abner, Undergraduate student (UW-Madison) (2021)
• An Li, Ph.D., Postdoctoral Fellow (2019-2021)
• Weiyi Guo, M.S., Graduate Student (MCW IDP) (2019)
• Dongwen Zhou, Ph.D. Postdoctoral Fellow/Research Scientist I (2014-2018)
• Aye Myat Myat Thinn, Ph.D. Predoctoral Fellow (MCW IDP) (2014-2018)
• Julia Williams, Undergraduate Student (MCW SPUR) (2018)
• Megan Wetzell, Undergraduate Student (UW-Madison) (2018)
• Magen Gates, Summer Student (MCW ROAD) (2017)
• Jiafu Liu, Ph.D. Postdoctoral Fellow (2011-2014)
• Chuanmei Zhang, Ph.D. Predoctoral Fellow (2012)
• Can Zhang, Ph.D. Visiting Scholar (2013)
• Xiulei Cai, Ph.D. Predoctoral Fellow (2014-2015)
• Yan Zhao, M.D. Visiting Scholar (2015-2016)
• Linzheng Shi, Summer Student (2013)
• Nada Haydar, B.S. Graduate Student (MCW IDP) (2012)

Click Here for a full list of publications from Dr. Jieqing Zhu.

Selected Publications

1. Heng Zhang, Zhengli Wang, Huong T.T. Nguyen, Abigail J. Watson, Qifang Lao, An Li, and Jieqing Zhu. Integrin α₅β₁ contributes to cell fusion and inflammation mediated by SARS-CoV-2 spike via RGD-independent interaction. Proc Natl Acad Sci USA, 120(50):e2311913120 (2023).
2. Heng Zhang, Daniel S. Zhu, and Jieqing Zhu. Family-wide analysis of integrin structures predicted by AlphaFold2. Computational and Structural Biotechnology Journal, 21:4497-4507 (2023).
3. Sevasti B. Koukouritaki, Aye Myat M. Thinn, Katrina J. Ashworth, Juan Fang, Haley S. Slater, Lily M. Du, Xavier Pillois, Alan T. Nurden, Jorge Di Paola, Jieqing Zhu*, David A. Wilcox*. A single F153Sβ3 mutation causes constitutive integrin αIIbβ3 activation in a variant form of Glanzmann thrombasthenia. Blood Advances, 7(13):3180-3191 (2023). (*Corresponding author)
4. Heng Zhang, Qifang Lao, Jue Zhang, Jieqing Zhu. Coagulopathy in COVID-19 and anticoagulation clinical trials. Best Practice & Research Clinical Haemotology, 35(3):101377 (2022).
5. Fu-Yang Lin, Jing Li, Yonghua Xie, Jianghai Zhu, Thi Thu Huong Nguyen, Yonghui Zhang*, Jieqing Zhu*, and Timothy A. Springer*. A general chemical principle for creating closure-stabilizing integrin inhibitors. Cell, 185(19):3533-3550. (2022) (*Corresponding author).
6. Danying Liao, Jesse Sundlov, Jieqing Zhu, Heng Mei, Yu Hu, Debra K. Newman, and Peter J. Newman. Atomic level dissection of the PECAM-1 homophilic binding interface: Implications for endothelial cell barrier function. Arterioscler Thromb Vasc Biol. 42(2):193-204 (2022).
7. Zhengli Wang and Jieqing Zhu. Structural determinants of the integrin transmembrane domain required for bidirectional signal transmission across the cell membrane. Journal of Biological chemistry, 297(5):101318 (2021).
8. Zhengli Wang and Jieqing Zhu. Measurement of Integrin Activation and Conformational Changes on the Cell Surface by Soluble Ligand and Antibody Binding Assays. Methods in Molecular Biology, 2217:3-15 (2021).
9. Behnaz Bayat, Annalena Traum, Heike Berghöfer, Jieqing Zhu, Gregor Bein, Ulrich Sachs, and Sentot Santoso. Current anti-HPA-1a standard antibodies react with the β3 integrin subunit but not with αIIbβ3 and αVβ3 complexes. Thrombosis and Haemostasis, 119 (11):1807-1815 (2019).
10. Huiying Zhi, Maria Therese Ahlen, Aye Myat Myat Thinn, Hartmut Weiler, Brian R. Curtis, Bjørn Skogen, Jieqing Zhu, and Peter J. Newman. Atomic-level dissection of the polyclonal immune response to the human platelet alloantigen, HPA-1a (PlA1): Implications for diagnosis, prophylaxis and treatment. Blood Advances, 2(21):3001-3011 (2018).
11. Aye Myat Myat Thinn, Zhengli Wang, Dongwen Zhou, Yan Zhao, Brian R. Curtis, and Jieqing Zhu. The autonomous conformational regulation of β₃ integrin and the conformation-dependent property of HPA-1a alloantibodies. Proc Natl Acad Sci USA, 115(39): E9105-E9114 (2018).
12. Dongwen Zhou, Aye Myat Myat Thinn, Yan Zhao, Zhengli Wang, and Jieqing Zhu. Structure of an extended β3 integrin. Blood, 132(9): 962-972 (2018).
13. Aye Myat Myat Thinn, Zhengli Wang, and Jieqing Zhu. The membrane distal regions of integrin α cytoplasmic domains contribute differently to integrin inside-out activation. Scientific Reports, 8(1): 5067 (2018).
14. Jieqing Zhu. Csk/CD148 and platelet SFK activation – a balancing act! Blood, 131(10):1042-1043 (2018).
15. Zhengli Wang, Aye Myat Myat Thinn, and Jieqing Zhu. A pivotal role for a conserved bulky residue at the α1-helix of αL integrin I domain in integrin ligand binding. Journal of Biological chemistry, 292(50): 20756-20768 (2017).
16. Xiulei Cai, Aye Myat Myat Thinn, Zhengli Wang, Hu Shan, and Jieqing Zhu. The importance of N-glycosylation on β3 integrin ligand binding and conformational regulation. Scientific Reports, 7(1): 4656 (2017).
17. Sentot Santoso, Hevi Wihadmadyatami, Tamam Bakchoul, Silke Werth, Nadia Al-Fakhri, Gregor Bein, Volker Kiefel, Jieqing Zhu, Peter J. Newman, Behnaz Bayat, Ulrich J. Sachs. Antiendothelial αvβ3 Antibodies Are a Major Cause of Intracranial Bleeding in Fetal/Neonatal Alloimmune Thrombocytopenia. Arterioscler Thromb Vasc Biol. 36(8): 1517-1524 (2016).
18. Cathy Paddock, Dongwen Zhou, Panida Lertkiatmongkol, Peter J. Newman, and Jieqing Zhu. Structural basis for PECAM-1 homophilic binding. Blood, 127(8): 1052-1061 (2016).
19. Jianghai Zhu, Jieqing Zhu, Daniel W. Bougie, Richard H. Aster, and Timothy A. Springer. Structural basis for quinine-dependent antibody binding to platelet integrin. Blood, 126(18): 2138-2145 (2015).
20. Jiafu Liu, Zhengli Wang, Aye Myat Myat Thinn, Yan-Qing Ma, and Jieqing Zhu. The dual structural roles of the membrane distal region of α integrin cytoplasmic tail during integrin inside-out activation. Journal of Cell Science 128(9): 1718-1731 (2015).
21. Chuanmei Zhang, Jiafu Liu, Xiuli Jiang, Nada Haydar, Can Zhang, Hu Shan, and Jieqing Zhu. Modulation of integrin activation and signaling by α1/α1’-helix unbending at the junction. Journal of Cell Science 126(24): 5735-5747 (2013).
22. Jieqing Zhu, Jianghai Zhu, Timothy A. Springer. Complete integrin headpiece opening in eight steps. Journal of Cell Biology 201(7): 1053-1068 (2013).
23. Yan-Feng Zhou, Edward T. Eng, Jieqing Zhu, Chafen Lu, Thomas Walz, and Timothy A. Springer. Sequence and structure relationships within von Willebrand factor. Blood 120(2): 449-458 (2012).
24. Daniel W. Bougie, Mark H. Rasmussen, Jieqing Zhu, Richard H. Aster. Antibodies causing thrombocytopenia in patients treated with RGD-mimetic platelet inhibitors recognize ligand-specific conformers of αIIbβ3 integrin. Blood 119(26): 6317-6325 (2012).
25. Jieqing Zhu, Won-Seok Choi, Joshua G. McCoy, Ana Negri, Jianghai Zhu, Sarasija Naini, Jihong Li, Min Shen, Wenwei Huang, Craig J. Thomas, Marta Filizola, Timothy A. Springer, and Barry S. Coller. Structure-guided design of a high affinity platelet integrin αIIbβ3 receptor antagonist that disrupts Mg²⁺ binding to the MIDAS. Science Translational Medicine 4(125): 125ra32 (2012) (Cover story).
26. Jieqing Zhu, Jianghai Zhu, Ana Negri, Davide Provasi, Marta Filizola, Barry S. Coller, and Timothy A. Springer. The closed headpiece of integrin αIIbβ3, and its complex with an aIIb-specific antagonist that does not induce opening. Blood 116(23): 5050-5059 (2010).
27. Jieqing Zhu, Bing-Hao Luo, Patrick Barth, Jack Schonbrun, David Baker, and Timothy A. Springer. The structure of a receptor with two associating transmembrane domains on the cell surface: integrin αIIbβ3. Molecular Cell 34(2): 234-249 (2009).
28. Jieqing Zhu, Christopher V. Carman, Minsoon Kim, Motomu Shimaoka, Timothy A. Springer, and Bing-Hao Luo. Requirement of α and β subunit transmembrane helix separation for integrin outside-in signaling. Blood 110(7): 2475-2483 (2007).
29. Jieqing Zhu, Brian Boylan, Bing-Hao Luo, Peter J. Newman, and Timothy A. Springer. Tests of the extension and deadbolt models of integrin activation. Journal of Biological chemistry 282(16): 11914-11920 (2007).
30. Jieqing Zhu, Xiuli Jiang, Yueyong Liu, Po Tien, and George F. Gao. Design and characterization of viral polypeptide inhibitors targeting Newcastle disease virus fusion. Journal of Molecular Biology 354(3): 601-613 (2005).
31. Jieqing Zhu, Gengfu Xiao, Yanhui Xu, Fang Yuan, Congyi Zheng, Yueyong Liu, Huimin Yan, David K. Cole, John I. Bell, Zihe Rao, Po Tien, and George F. Gao. Following the rule: formation of the 6-helix bundle of the fusion core from severe acute respiratory syndrome coronavirus spike protein and identification of potent peptide inhibitors. Biochem. Biophys. Res. Commun. 319(1): 283-288 (2004).
32. Jieqing Zhu, Pengyun Li, Tinghe Wu, Feng Gao, Yi Ding, Catherine W-H Zhang, Zihe Rao, George F. Gao, and Po Tien. Design and analysis of post-fusion 6-helix bundle construct of heptad repeat regions from Newcastle disease virus F protein. Protein Engineering 16(5): 373-379 (2003).
33. Jieqing Zhu, Catherine W.-H. Zhang, Zihe Rao, Po Tien, and George F. Gao. Biochemical and biophysical analysis of heptad repeat regions from the fusion protein of Menangle virus, a newly emergent paramyxovirus. Archives of Virology 148(7): 1301-1316 (2003).
34. Jieqing Zhu, Catherine W.-H. Zhang, Yipeng Qi, Po Tien, and George F. Gao. The fusion protein core of measles virus forms stable coiled coil trimer. Biochem. Biophys. Res. Commun. 299(5): 897-902 (2002).