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Yan-Qing Ma, PhD

Yan-Qing Ma, PhD

Investigator

Assistant Professor
Department of Biochemistry
Medical College of Wisconsin

Education and Training

Doctoral Training
Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences

 Postdoctoral Training
Lerner Research Institute, Cleveland Clinic

Contact Us

Yan-Qing Ma, PhD

Investigator
Email (414) 937-3881 Fax: (414) 937-6284

  • Research Interests

    Thrombosis, Hemostasis and Vascular Biology

    The integrin family receptors deliver bidirectional signals (inside-out and outside-in) across the plasma membrane to modulate cell adhesion, migration, proliferation, differentiation and apoptosis. The integrin signaling comprises a series of molecular events occurring within cells that can steer integrins to dynamically regulate the dialogue between the extracellular milieu and the cytoplasmic signal cascades via integrin conformational changes. Mechanistically, integrin activity can be tightly modulated by some key integrin cytoplasmic tail-binding proteins (CTBPs), and the interactive cooperation between the integrin cytoplasmic tails and the integrin CTBPs virtually defines the integrin activation states and the functional consequences. Importantly, malfunctions of integrins, resulted from functional defects of either integrins themselves or the integrin CTBPs, often lead to severe pathological conditions, such as infections, bleeding disorders and angiogenic dysregulations. 

    The long-term goal of our research is to interpret the detailed molecular mechanisms of integrin activation and explore the therapeutic value for integrin-associated vascular diseases. Currently, our study focuses on kindlin-3, one of the key integrin CTBPs. Kindlin-3 is mainly expressed in hematopoietic cells and plays an important role in supporting integrin function in blood cells. The absence of kindlin-3 expression in blood cells causes type-III leukocyte adhesion deficiency in humans, characterized by bleeding disorders and recurrent bacterial infections. Specifically, our ongoing projects are investigating how kindlin-3 in platelets/neutrophils functions at the interface of inflammation and thrombosis under pathological conditions, such as deep vein thrombosis and sepsis. The experimental approaches employed in our laboratory range from biochemical analyses, molecular biology, and cellular mechanisms, to small animal models.

  • Grant Support
    • NIH Grant R01 HL131654, 06/01/2016-02/28/2020, Kindlin-3 signaling in blood cells
    • BCW, Blood Center Research Fund, 2011-
  • Lab

    Zhen Xu, PhD
    Research Scientist II

    Marjorie Kipp
    Research Technologist

    Huong Nguyen
    Postdoctoral Fellow

    Former lab trainees:
    HuiHui Liu, PhD, Research Fellow
    Jiayi Cai, MD, Visiting Scholar
    Beiwen Ni, MD, Visiting Scholar
    Shuzhen Liu, PhD, Research Fellow

    Postdoctoral position available:

    One Postdoctoral/Research Associate position is available in the laboratory. The successful candidate will employ mouse models, ex vivo analyses, cellular/biochemical/molecular approaches to dissect the mechanisms employed by kindlin-3 to regulate neutrophil/platelet functions. Applicants should have a PhD and/or MD degree, be proficient in English, and be able to work independently. A very competitive annual salary and an attractive benefit package will be offered.

    Interested candidates should submit resume and a cover letter to: Dr. Yan-Qing Ma, PhD, Blood Research Institute, BloodCenter of Wisconsin; email: yanqing.ma@bcw.edu. Review of applicants will begin immediately, and continue until the position is filled. BloodCenter of Wisconsin is an internationally recognized leader in vascular biology, thrombosis, and hemostasis research, and Blood Research Institute provides state-of-the-art facilities and offers an excellent environment for scientific interactions and comprehensive postdoctoral fellow training programs. 

  • Publications
    • Ma Y.Q. and Geng JG. Heparan sulfate-like proteoglycans mediate adhesion of human malignant melanoma A375 cells to P-selectin under flow. J. Immunol. 165: 558- 565; 2000.
    • Ma Y.Q. and Geng JG. Obligatory requirement of sulfation for P-Selectin binding to human salivary gland carcinoma Acc-M cells and breast carcinoma ZR-75-30 cells. J. Immunol. 168:1690-1696; 2002.
    • Ma Y.Q., Plow EF and Geng JG. P-selectin binding to P-selectin glycoprotein ligand-1 induces an intermediate state of αMβ2 activation and acts cooperatively with extracellular stimuli to support maximal adhesion of human neutrophils. Blood 104: 2549-2556; 2004.
    • Plow EF, Pesho M and Ma Y.Q. “Integrin αIIbβ3”, chapter 8 in: Platelets 2/e, Michelson, 2007.
    • Ma Y.Q., Yang, J., Pesho, M., Vinogradova O., Qin, J. and Plow EF. Regulation of integrin alphaIIbbeta3 activation by distinct regions of its cytoplasmic tails. Biochemistry 45(21):6656-62; 2006.
    • Ma Y.Q., Qin J and Plow EF. Platelet Integrin αIIbβ3: Activation mechanisms. Journal of Thrombosis and Haemostasis 5: 1345-1352; 2007.
    • Plow EF and Ma Y.Q. Inside-out, outside-in: what’s the difference? Blood 109(8): 3128-29; 2007.
    • Shi X., Ma Y.Q., Tu Y., Chen K., Wu S., Fukuda K., Qin J., Plow EF and Wu C. Mig-2/integrin interaction strengthens cell-matrix adhesion and modulates cell motility. J. Biol. Chem. 282(28):20455-66; 2007.
    • Ma Y.Q., Qin J., Wu C. and Plow EF. Kindlin-2 (Mig-2): a co-activator of beta3 integrins. J. Cell Biol. 181: 439-446; 2008.
    • Goksoy E.#, Ma Y.Q.#, Wang X., Kong X., Perera D., Plow EF and Qin J. (2008) Structural basis for the autoinhibition of talin in regulating integrin activation. Mol Cell. 31(1):124-33; 2008. (#Equal contributions)
    • Malinin NL, Zhang L., Chio J., Ciocea A., Razorenova O, Ma, Y.Q., Podrez EA, Tosi M., Lennon DP, Caplan AI, Shurin SB, Plow EF and Byzova TV. A point mutation in KINDLIN3 ablates activation of three integrin subfamilies in humans. Nature Medicine 15(3):313-8; 2009.
    • Ithychanda SS, Das M., Ma Y.Q., Ding K., Wang X., Gupta S., Wu C., Plow EF and Qin J. Migfilin: a molecular switch in regulation of integrin activation. J. Biol. Chem. 284(7): 4713-4722; 2009.
    • Plow EF, Ma Y.Q., Byzova TV and Jun Q. Platelet Aggregation: A Brief Historical and Molecular Perspective. Journal of Thrombosis and Thrombolysis 26(1):68-70; 2009.
    • Yang J., Ma Y.Q., Rage RC, Misra S., Plow EF and Qin J. Structure of an integrin αIIbβ3 transmembrane-cytoplasmic heterocomplex provides insight into integrin activation. Proc Natl Acad Sci U S A. 106(42):17729-34; 2009.
    • Bialkowska K., Ma Y.Q., Bledzka K., Sossey-Alaoui, K., Izem L., Zhang X., Malinin N., Qin J., Byzova T and Plow EF. The integrin co-activator kindlin-3 is expressed and functional in a non-hematopoietic cell, the endothelial cell. J. Biol. Chem. 285(24):18640-9; 2010.
    • Bledzka K., Bialkowska K., Nie H., Qin J., Byzova T., Wu, C., Plow EF and Ma Y.Q. Tyrosine phosphorylation of beta3 integrin regulates kindlin-2 binding and integrin activation. J. Biol. Chem. 285(40):30370-4; 2010.
    • Pluskota E., Dowling JJ, Gordon N., Golden J., Szpak D., West ZX., Nestor C., Ma Y.Q., Bialkowska K., Byzova T and Plow EF. The integrin co-activator kindlin-2 plays a critical role in angiogenesis in mice and zebrafish. Blood 117(18):4978-87; 2011.
    • Perera, H.D., Ma, Y.Q., Yang, J., Hirbawi, J. Plow, E.F., and Qin, J. Membrane binding of the N-terminal ubiquitin-like domain of kindlin-2 is crucial for its regulation of integrin activation. Structure, 19(11):1664-71; 2011.
    • Liu J., Fukuda K., Xu Z., Ma Y.Q., Hirbawi J., Plow EF and Qin J. Structural basis of phosphoinositide binding to Kindlin-2 pleckstrin homology domain in regulating integrin activation. J. Biol. Chem. 286(50):43334-42; 2011.
    • Bledzka K., Liu J., Xu Z., Perera HD., Yadav SP., Bialkowska K., Qin J., Ma Y.Q. and Plow EF. Spatial coordination of kindlin-2 with talin head domain in interaction with integrin β cytoplasmic tails. J. Biol. Chem. 287(29):24585-94. 2012.
    • Bledzka K., Pesho M., Ma, Y.Q., and Plow, E.F. Integrin αIIbβ3, chapter 8 in: Platelets 3/e. Michelson. 2013.
    • Xu, Z., Gao, J., Hong, J., and Ma, Y.Q. Integrity of Kindlin-2 FERM subdomains is required for supporting integrin activation. BBRC. 434(2):382-7. 2013.
    • Pluskota E., Ma, Y., Bledzka, K.M., Bialkoska, K., Soloviev, D.A., Szpak, D., Podrez, E.A., Fox, P.L., Hazen, S.L., Dowling, J.J., Ma, Y.Q. and Plow, E.F. Kindlin-2 regulates hemostasis by controlling endothelial cell surface expression of ADP/AMP catabolic enzymes via a clathrin-dependent mechanism. Blood 122(14):2491-9. 2013.
    • Xu, Z., Chen, X., Zhi, H., Gao, J., Bialkowska, K., Byzova, T.V., Pluskota, E., White, G.C., Liu, J., Plow, E.F., and Ma Y.Q. Direct interaction of kindlin-3 with integrin αIIbβ3 in platelets is required for supporting arterial thrombosis in mice. Arterioscler. Thromb. Vasc. Biol. 34(9):1961-9. 2014
    • Liu, J., Wang Z., Thinn A.M., Ma Y.Q., Zhu J. The dual structural role of the membrane distal region of integrin cytoplsamic tails in integrin inside-out activation. Journal of Cell Science 128(9):1718-31. 2015
    • Xu, Z., Cai, J., White, G.C., Chen, F. and Ma Y.Q. Interaction of kindlin-3 and β2-integrins differentially regulates neutrophil recruitment and NET release in mice. Blood 126(3):373-7. 2015 
    • Gao J., Huang M., Lai J., Mao K., Sun P., Cao Z, Hu, Y., Zhang Y., Schulte M.L., Jin C., Wang J., White G., Xu Z. and Ma Y.Q. Kindlin supports integrin αIIbβ3 activation by interacting with paxillin. Journal of Cell Science 30(21): 3764-75. 2017
    • Xu Z., Ni B., Cao Z., Zielonka J., Gao J., Chen F., Kalyanaraman B., White G.C., Ma Y.Q. Kindlin-3 negatively regulates the release of neutrophil extracellular traps. Journal of Leukocyte Biol. 2018 [Epub ahead of print]
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