Research
Stem cells possess the unique ability to self-renew and to differentiate into multiple tissue types, and thus are ideal source of cells for tissue repair and regeneration. However, successful stem cell-based therapy depends on our thorough understanding of stem cell biology, in particular, their ability to proliferate and differentiate within an immune-competent host.
Our research program is comprised of three distinct yet complementary projects: 1) molecular basis that regulates integrin activation, receptor-ligand recognition, and cell migration within inflammatory environments (Fig. 1); 2) cellular mechanisms that modulate immune activation vs. suppression (Fig. 2); and 3) stem cell biology (Fig. 3). The information generated from these studies can assist us better understand the pathogenesis of a number of challenging diseases, such as sepsis, atherosclerosis, rheumatoid arthritis, and other autoimmune diseases, and develop potential therapies for clinical applications.
Our current research interests include:
- Structure-function of integrins: ligand binding and cell migration.
- Immune modulation: macrophages and tolerigenic dendritic cells.
- Immune Suppression: PAR-1, S1P and S1P receptors.
- Tissue repair and regeneration: iPS, MSC and EPC
- Human patients with defective integrin activation.
Migration | 
Immune Tolerance |
Lab Techniques
- Various knockout and transgenic mice for evaluating
 the roles of different proteins and receptors in health and disease.
- Commonly used mouse models in the laboratory
Balloon angioplasty model
Myocardial infarction
Ectopic bone and bone marrow regeneration
Oral and intravenous immune tolerance model
- Adoptive cell transfer and bone marrow transplantation.
- Laser scanning confocal fluorescence microscopy and FRET.
- Live cell imaging.
- FACS cell sorting to enrich a particular stem cell population.
- Real time qRT-PCR, 2D PAGE, and gene microarray.
- Protein expression in E.coli, yeasts, Sf9 insect cells, and eukaryotic cells.
Publications
Selected from a total of 44 publications
- Plow, E.F. and Zhang, L. A MAC-1 attack: integrin functions directly challenged in knock-out mice. Journal of Clinical Investigation 99:1145-1146, 1997.
- Simon, D.I., Chen, Z., Xu, H., Li, C.Q., Dong, J., McIntire, L.V., Ballantyne, C.M., Zhang, L., Furman, M.I., Berndt, M.C., & Lopez, J.A. Platelet glycoprotein ibalpha is a counterreceptor for the leukocyte integrin Mac-1 (CD11b/CD18). Journal of Experimental Medicine, 192: 193-204. 2000.
- Xiong, Y. M., & Zhang, L. Structure-function of the putative I-domain within the integrin b2 subunit. Journal of Biological Chemistry, 276: 19340-19349. 2001.
- Xiong, Y. M., Chen, J., & Zhang, L. Modulation of CD11b/CD18 adhesive activity by its extracellular membrane-proximal regions. Journal of Immunology, 171: 1042-1050. 2003.
- Cao, C., Lawrence, D.A., Strickland, D., and Zhang, L. A specific role of integrin mac-1 in accelerated macrophage efflux to the lymphatics. Blood 106: 3234-3241, 2005.
- Miura, Y., Miura, M., Gronthos, S., Allen, M.R., Cao, C., Uveges, T.E., Bi, Y., Shi, S., and Zhang, L. Integrin beta2 is a novel surface marker for bone marrow stromal stem cells and plays an important role in osteogenic differentiation in vivo. Proceedings of the National Academy of Sciences 102:14022-14027. 2005.
- Cao, C., Lawrence, D.A., Li, Y., Von Arnim, C.A., Herz, J., Su, EJ, Makarova, A, Hyman, B.T., D.A., Strickland, D., and Zhang, L. Endocytic receptor LRP together with tPA and PAI-1 coordinates Mac-1-dependent macrophage migration. The EMBO Journal, 25:1860-1870, 2006.
- Miura, Y, Gao, Z, Miura, M, Seo, B.M., Sonoyama, W, Chen, W, Gronthos, S, Zhang, L, and Shi, S. Mesenchymal Stem Cell-Organized Bone Marrow Elements: An Alternative Hematopoietic Progenitor Resource. Stem Cells 24:2428-2436, 2006.
- Ehirchiou, D, Xiong, Y, Xu, G, Chen, W, Shi, Y, and Zhang, L CD11b Facilitates the Development of Peripheral Tolerance by Suppressing Th17 Differentiation. Journal Experimental Medicine 204:1519-24 2007.
- Bi, Y, Ehirchiou, D, Kilts, TM, Inkson, CA, Embree, MC, onoyama, W, Li, L, Leet, AI, Seo, B, Zhang, L, Shi, S, and Young, MF Identification of tendon stem/progenitor cells and the role of the extracellular matrix in their niche. Nature Medicine, 13:1219-1227 2007
- Choi EY, Orlova VV, Fagerholm SC, Nurmi SM, Zhang, L, Ballantyne CM, Gahmberg CG, Chavakis T. Regulation of LFA-1-dependent inflammatory cell recruitment by Cbl-b and 14-3-3 proteins. Blood 111:3607-14, 2008.
- Li, Y, Cao, C, Jia, W, Yu, L, Mo, M, Wang, Q, Huang, Y, Lim, J, Ishihara, M, Wells, L, Azadi, P, Robinson, H, He, Y, Zhang, L and Mariuzza, RA. Structure of the F-spondin domain of mindin, an integrin ligand and pattern recognition molecule. EMBO J. 28:286-97, 2009.
- Malinin, N, Zhang, L, Choi, J, Ciocea, A, Razorenova, O, Ma, Y, Podrez, EA, Tosi, M, Lennon, DP, Caplan, AI, Shurin, SB, Plow, EF, and Byzova, TV, A point mutation in kindlin-3 ablates activation of three integrin subfamilies in humans. Nature Medicine, 2009 Feb 22. [Epub ahead of print]
Personal History
I received my PhD in Biochemistry and Molecular Biology from the University of Notre Dame, Notre Dame, Indiana. I then worked at the Cleveland Clinic, the Holland Laboratory, and the George Washington University. I joined the University of Maryland School of Medicine in 2004. My research program has been continuously funded by the National Institute of Health and the American Hearst Association. I'm also associated with two training grants from the National Institute of Health.
Laboratory PersonnelBack to All Faculty |