We study integrin signaling in blood cells. Integrin family receptors deliver bidirectional signaling (inside-out and outside-in) across the cell plasma membrane, modulating cell adhesion, migration, proliferation, differentiation, and other functions. Integrin signaling involves a series of molecular events within cells that enable integrins to bridge the crosstalk between the extracellular milieu and cytoskeletal changes, as well as cytoplasmic signaling cascades. Integrin activation is tightly regulated by integrin cytoplasmic tail binding proteins (ICBPs). The interaction between integrins and ICBPs defines the activation states and functional activities of integrins. Dysfunction of integrin signaling often leads to integrin-associated pathological conditions, including inflammatory defects and bleeding disorders. The long-term goal of our research is to elucidate the detailed molecular mechanisms regulating integrin signaling and to explore novel and safer therapeutic strategies for preventing and treating integrin-associated diseases, such as inflammation and thrombosis.

The ongoing research in our laboratory focuses on Kindlin-3, an essential integrin signaling adaptor molecule and one of the key ICBPs expressed in cells of hematopoietic origin. Kindlin-3 plays a critical role in supporting integrin signaling in blood cells. Kindlin-3 deficiency causes type-III leukocyte adhesion deficiency (LAD-III) in humans, characterized by severe bleeding disorders and recurrent infections. Specifically, we are investigating the novel role of Kindlin-3 in platelets and myeloid cells in modulating immunothrombosis under various pathological conditions, including deep vein thrombosis and endotoxemia. Our experimental approaches range from biochemical and cellular analyses to small animal models. Our study may facilitate the development of more specific and safer strategies for treating immunothrombotic complications across a wide range of diseases.

Ma, YanQing. Research Fig. 02-18-22

• NIH-NHLBI, 1R01HL15730, Kindlin-3 Signaling in Platelets. Role: PI (2022-2025)
• NIH-NHLBI, 1R01HL16086, Kindlin-3 Signaling in Neutrophils. Role: PI (2022-2026)
• Versiti Joan Cox Gill Clinic & Translational Pilot Award, Endotoxemia and deep vein thrombosis, 2024-2025

Zhen Xu, PhD
Research Scientist

Zhiwei Xu, PhD
Research Scientist

Marjorie Kipp
Research Technologist

Ying Zhou
Research Technologist

Positions Available:

Postdoctoral Laboratory Opportunities:

One Postdoctoral Fellow position is available at Versiti Blood Research Institute (www.versiti.org) to conduct NIH-funded research projects. The successful candidate will employ biochemical and cellular approaches together with small animal models to study the mechanistic role of novel Kindlin-3 signaling in platelets and innate immune cells in modulating immunothrombosis. The study may lead to new opportunities for developing more specific and safer 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 with research experience in platelet biology and/or immunology and be able to 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 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 (yma@versiti.org). Review of applicants will begin immediately and continue until the position is filled.

Technologist Laboratory Opportunities:

One Research Technologist position is available at Versiti Blood Research Institute (www.versiti.org). The successful candidate should have some basic experimental skills in Cell Biology and Biochemistry, including but not limited to cell culture, western blotting, PCR, small animal handling, etc. Previous work experience in the field 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 (yma@versiti.org). Review of applicants will begin immediately and continue until the position is filled.

Versiti Blood Research Institute (VBRI), located in Milwaukee of the state Wisconsin in the US, is an internationally recognized leader in hematology, immunology, vascular biology, and stem cell research. It is adjacent to the Medical College of Wisconsin on the campus of the Milwaukee Regional Medical Center, which is also home to Milwaukee’s major hospitals, Children’s Hospital and Froedtert Hospital. The proximity of VBRI to the basic and clinical research programs promotes productive environment for collaboration. VBRI provides an excellent research environment, state-of-the-art facilities, and comprehensive training programs. As the largest city in the 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.

Click here to apply for positions on the Versiti Careers website.

Selected Publications

• 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. 
• Liu C., Zhou Y., Zhou Y., Xu Z. and Ma Y.Q. Kindlin-3 in immune cells is required to suppress prostate cancer tumor growth in mice. Anticancer Research 42(3):1217-1220. 2022 
• Xu Z., Jobe S.M., Ma Y.Q.‡, Shavit J.A. A novel leukocyte adhesion deficiency type III mutation manifests functional important of the compact FERM domain in kindlin-3. Journal of Thrombosis and Hemostasis 22(2):558-564. 2024
• Xu Z., Zhou Y., Yu H., Chen X., Ma Y.Q. Myosin light chain 6 (Myl6) interacts with kindlin-3 and support integrin αIIbβ3 activation in platelets in mice. Journal of Thrombosis and Hemostasis 2024. DOI: 10.1016/j.jtha.2024.01.007 (Online ahead of print)

Positions Available:

Click Here for Job Posting Site

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 (yma@versiti.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.