Yan-Qing Ma, PhD
The integrin family receptors deliver bidirectional signaling (inside-out and outside-in) across plasma membrane, by which they modulate cell adhesion, migration, proliferation, differentiation, and apoptosis. Integrin signaling comprises a series of molecular events within cells that steer integrins to bridge the crosstalk between the extracellular milieu and the cytoplasmic signaling cascades. Integrin activation and activity are tightly modulated by integrin cytoplasmic tail binding proteins (ICBPs). The dialogue between integrins and the ICBPs defines the integrin activation states and functional activities. Malfunction of integrin signaling often leads to integrin-associated pathological alterations, such as inflammatory defect and bleeding disorder. The long-term goal of our research is to understand the detailed molecular regulations of integrin signaling and explore novel therapeutic opportunities for preventing and treating integrin-associated diseases.
The ongoing research in our laboratory focuses on an important signaling adaptor molecule - Kindlin-3, which is one of the key ICBPs expressed in cells of hematopoietic origin. Kindlin-3 plays an essential role in supporting integrin signaling in blood cells. Deficiency of kindlin-3 causes type-III leukocyte adhesion deficiency (LAD-III) in human patients, marked with severe bleeding disorder and recurrent infections. Specifically, we investigate the mechanistical role of Kindlin-3 in platelets and myeloid cells in immunothrombosis under different pathological conditions, such as deep vein thrombosis and sepsis. The experimental approaches employed in our laboratory range from biochemical analysis, molecular biology, cellular mechanism, to small animal models. Our study may facilitate the development of more specific strategies for treating immunothrombotic complications in a whole host of diseases, including widespread COVID-19.
Ma, YanQing. Research Fig. 02-18-22
- ASH Bridge Grant, Kindlin signaling in platelets. Role: PI (2021-2022)
- NIH-NHLBI, 1R01HL15730, Kindlin-3 Signaling in Platelets. Role: PI (2022-2025)
- NIH-NHLBI, 1R01HL16086, Kindlin-3 Signaling in Neutrophils. Role: PI (2022-2026)
Zhen Xu, PhD
Research Scientist II
Former lab trainees:
Bin Wang, PhD, Postdoctoral Fellow
HuiHui Liu, PhD, Postdoctoral Fellow
Jiayi Cai, MD, Visiting Scholar
Beiwen Ni, MD, Visiting Scholar
Shuzhen Liu, PhD, Postdoctoral Fellow
Xiaofeng Shi, MD, Postdoctoral Fellow
Huong Nguyen, PhD, Postdoctoral Fellow
There are currently open positions in the Ma Lab, 2 Postdoctoral Fellows and 2 Research Technicians. See the Open Positions menu on this page for more detail or click here to visit them on the Versiti Careers website.
- Ma YQ and Geng JG. Heparan sulfate-like proteoglycans mediate adhesion of human malignant melanoma A375 cells to P-selectin under flow. J Immunol. 2000;165:558-565.
- Ma YQ 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. 2002;168:1690-1696.
- Ma YQ, Plow EF, 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. 2004;104:2549-2556.
- Ma YQ, Yang J, Pesho M, Vinogradova O, Qin J, Plow EF. Regulation of integrin alphaIIbbeta3 activation by distinct regions of its cytoplasmic tails. Biochemistry 2006;45(21):6656-62.
- Shi X, Ma YQ, Tu Y, Chen K, Wu S, Fukuda K, Qin J, Plow EF, Wu C Mig-2/integrin interaction strengthens cell-matrix adhesion and modulates cell motility. J Biol Chem 2007;282(28):20455-66.
- Ma YQ, Qin J, Wu C, Plow EF. Kindlin-2 (Mig-2): a co-activator of beta3 integrins. J Cell Biol 2008;181:439-446.
- Goksoy E#, Ma YQ#, Wang X, Kong X, Perera D, Plow EF, Qin J. Structural basis for the autoinhibition of talin in regulating integrin activation. Mol Cell 2008;31(1):124-33.
(# Equal contributions)
- Malinin NL, Zhang L, Chio J, Ciocea A, Razorenova O, Ma YQ, Podrez EA, Tosi M, Lennon DP, Caplan AI, Shurin SB, Plow EF, Byzova TV. A point mutation in KINDLIN3 ablates activation of three integrin subfamilies in humans. Nature Medicine 2009;5(3):313-8.
- Ithychanda SS, Das M, Ma YQ, Ding K, Wang X, Gupta S, Wu C, Plow EF, Qin J. Migfilin: a molecular switch in regulation of integrin activation. J Biol Chem 2009;284(7): 4713-4722.
- Yang J, Ma YQ, Rage RC, Misra S, Plow EF, Qin J. Structure of an integrin αIIbβ3 transmembrane-cytoplasmic heterocomplex provides insight into integrin activation. Proc Natl Acad Sci U S A. 2009;106(42):17729-34.
- Bialkowska K, Ma YQ, Bledzka K, Sossey-Alaoui K, Izem L, Zhang X, Malinin N, Qin J, Byzova T, Plow EF. The integrin co-activator kindlin-3 is expressed and functional in a non-hematopoietic cell, the endothelial cell. J Biol Chem. 2010;285(24):18640-9.
- Bledzka K, Bialkowska K, Nie H, Qin J, Byzova T, Wu C, Plow EF, Ma YQ. Tyrosine phosphorylation of beta3 integrin regulates kindlin-2 binding and integrin activation. J Biol Chem. 2010;285(40):30370-4.
- Pluskota E, Dowling JJ, Gordon N, Golden J, Szpak D, West ZX, Nestor C, Ma YQ, Bialkowska K, Byzova T, Plow EF. The integrin co-activator kindlin-2 plays a critical role in angiogenesis in mice and zebrafish. Blood 2011;117(18):4978-87.
- Perera HD, Ma YQ, Yang J, Hirbawi J, Plow EF, Qin J. Membrane binding of the N-terminal ubiquitin-like domain of kindlin-2 is crucial for its regulation of integrin activation. Structure 2011;19(11):1664-71.
- Liu J, Fukuda K, Xu Z, Ma YQ, Hirbawi J, Plow EF, Qin J. Structural basis of phosphoinositide binding to Kindlin-2 pleckstrin homology domain in regulating integrin activation. J Biol Chem 2011;286(50):43334-42.
- Bledzka K, Liu J, Xu Z, Perera HD, Yadav SP, Bialkowska K, Qin J, Ma YQ, Plow EF. Spatial coordination of kindlin-2 with talin head domain in interaction with integrin β cytoplasmic tails. J Biol Chem 2012; 287(29):24585-94.
- Pluskota E, Ma Y, Bledzka KM, Bialkoska K, Soloviev DA, Szpak D, Podrez EA, Fox PL, Hazen SL, Dowling JJ, Ma YQ, Plow EF. Kindlin-2 regulates hemostasis by controlling endothelial cell surface expression of ADP/AMP catabolic enzymes via a clathrin-dependent mechanism. Blood 2013;122(14):2491-9.
- Xu Z, Chen X, Zhi H, Gao J, Bialkowska K, Byzova TV, Pluskota E, White GC, Liu J, Plow EF, Ma YQ. Direct interaction of kindlin-3 with integrin αIIbβ3 in platelets is required for supporting arterial thrombosis in mice. Arterioscler Thromb Vasc Biol. 2014; 34(9):1961-9.
- Xu Z, Cai J, White GC, Chen F, Ma YQ. Interaction of kindlin-3 and β2-integrins differentially regulates neutrophil recruitment and NET release in mice. Blood 2015;126(3):373-7.
- Gao J, Huang M, Lai J, Mao K, Sun P, Cao Z, Schulte ML, Hu Y, Zhang Y, Ni B, Jin C, Wang J, Chen F, White G, Xu Z, Ma YQ. Kindlin supports integrin αIIbβ3 activation by interacting with paxillin. J Cell Sci 2017;128(9): 1718-31.
- Xu Z, Ni B, Cao Z, Zielonka J, Gao J, Chen F, Kalyanaraman B, White GC, Ma YQ. Kindlin-3 negatively regulates the release of neutrophil extracellular traps. J Leukocyte Biol 2018;104(3):597-602.
- Yan Y, Yang H, Hu X, Zhang Z, Ge S, Xu Z, Gao J, Liu J, White GC, Ma YQ. Kindlin-3 in platelets and myeloid cells differentially regulates deep vein thrombosis in mice. Aging (Albany NY) 2019;11(17):6951-9.
- Sun J, Xiao D, Ni Y, Zhang T, Cao Z, Xu Z, Nguyen H, Zhang J, White GC, Ding J, Ma YQ, Xu Z. Structure basis of the FERM domain of kindlin-3 in supporting integrin αIIbβ3 activation in platelets. Blood Adv 2020 Jul 14;4(13):3128-3135.
- Zhu R, Yan T, Feng Y, Liu Y, Cao H, Peng G, Yang Y, Xu Z, Liu J, Hou W, Wang X, Li Z, Deng L, Wang S, Li J, Han Q, Li H, Shan G, Cao Y, An X, Yan J, Zhang Z, Li H, Qu X, Zhu J, Zhou S, Wang J, Zhang F, Gao J, Jin R, Xu D, Ma YQ, et al, Mesenchymal stem cell treatment improves outcome of COVID-19 patients via multiple immunomodulatory mechanisms. Cell Res. 2021; 31(12):1244-62.
- Nguyen H, Xu Z, Shi X, Liu S, Schulte ML, White GC, Ma YQ. Paxillin binding to the PH domain of kindlin-3 in platelets is required to support integrin αIIbβ3 outside-in signaling. J Thromb Haemost. 2021; 19(21):3126-38.
Postdoctoral positions available:
Two (2) Postdoctoral Fellow positions are available at Versiti Blood Research Institute to conduct NIH-funded research projects. The successful candidates will use biochemical/structural/cellular approaches and small animal models to study the mechanistic role of Kindlin-3 in platelets and innate immune cells in immunothrombosis, which may lead to novel opportunities for developing more specific strategies for preventing and treating immunothrombotic complications in a whole host of diseases, including widespread COVID-19. Applicants should have a PhD and/or an MD degree in closely related fields and can perform experiments independently with a highly motivated attitude. Strong verbal and written communication skills in English are required. A very competitive annual salary and benefit package (including medical and dental insurance) will be offered.
Technician/Technologist positions available:
Two (2) Research Technician/Technologist positions are available at Versiti Blood Research Institute. The successful candidates should have some basic experimental skills in Cell Biology and/or Biochemistry, including but not limited to cell culture, western blotting, PCR, small animal handling, etc. Previous work experience in the field of Immunology and/or Hematology is preferred. Applicants should have a bachelor’s degree or master’s degree with strong time management and efficient written/oral communication skills. A very competitive annual salary and benefit package will be offered.
Interested candidates should send a cover letter, an updated CV, and contact information of three references to Dr. Yan-Qing Ma by email (firstname.lastname@example.org). Review of applicants will begin immediately and continue until the positions are filled.
Versiti Blood Research Institute located in Milwaukee is an internationally recognized leader in hematology, immunology, and stem cell research areas. The institute provides an excellent research environment, state-of-the-art facilities, and comprehensive training programs for postdoctoral fellows and graduate students. As the largest city in the US state of Wisconsin, Milwaukee is a place where its residents truly love to live and enjoy, with its diversity, the richness of the arts in the community, and the low cost-of-living.