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Yong Zhao, MD, Ph.D.
Office and Laboratory Location:
University of Illinois at Chicago, Department of Medicine
Section of Endocrinology, Diabetes and Metabolism
Mailing Address: 1819 West Polk St., M/C 640
Express Delivery (Fed Ex-UPS): 835 S. Wolcott, 6th Floor, Room E625
Chicago, IL 60612
MD - Shandong Weifang Medical Science, China
MS - Shandong Academy of Medical Science, China
PhD - Shanghai Second Military Medical University, China
Diabetes imposes a large burden on family and society and presents an important challenge to find more effective therapies. To achieve this goal, Dr. Zhao laboratory is actively pursuing the following research programs:
Reversal of Type 1 Diabetes by Cord Blood Stem Cell-Educated Regulatory T Cells
Autoimmune destruction of pancreatic islet beta cells is a crucial issue in type 1 diabetes (T1D). It is essential to fundamentally control the autoimmunity for treatment of T1D. Regulatory T cells (Tregs) play a pivotal role in maintaining self-tolerance through their inhibitory impact on autoreactive effector T cells. An abnormality of Tregs is associated with initiation of progression of T1D. Thus, the manipulation of Tregs for treatment of T1D is an attractive approach. We identified a novel type of stem cells from human umbilical cord blood (designated cord blood stem cells, CB-SC), with multiple potential of differentiation. Notably, we found that CB-SC display CB-SC displayed immuno-modulatory effects on human allogeneic T lymphocytes. Based on these works, recently we have demonstrated that treatment with CB-SC-educated CD4CD62L Tregs can reverse overt diabetes, not only by controlling the autoimmunity but also by promoting beta cell regeneration leading to the restoration of euglycemia in an autoimmune-caused diabetic NOD mouse model. These autologous CD4CD62L Tregs can be readily generated by co-culture with allogeneic CB-SC for therapeutic applications without concern for immune rejection. The whole procedure is also safe and cost-effective. Thus, these findings may have implications for the development of novel human therapies.
Human Blood-Derived Insulin-Producing Cells
The shortage of insulin-producing cells is the common issue for both type 1 and late-stage of type 2 diabetic patients. Our recent studies have demonstrated that insulin-producing cells exist in adult human blood, designated peripheral blood-derived insulin-producing cells (PB-IPC). Using attachment, PB-IPC can be isolated and expanded in a large scale. Notably, in vitro and in vivo characterization revealed that PB-IPC demonstrated characteristics of islet beta cell progenitors including the expression of beta cell-specific insulin gene transcription factors and prohormone convertases, production of insulin, formation of insulin granules, and the ability to reduce hyperglycemia and migrate into pancreatic islets after transplantation into the diabetic mice. Application of PB-IPC is easy to access, culture, expand, and differentiate, very cost-effective and safe, without any ethical issues and immune rejection. These findings may open up new avenues for autologous blood stem cell-based therapies for diabetes.
Selected Recent Publications and Manuscripts in Review:
Yong Zhao, Brian Lin, Robert Darflinger, Yongkang Zhang, Mark Holterman, Randal A. Skidgel. (2009) Human cord blood stem cell-modulated regulatory T lymphocytes reverse the autoimmune-caused type 1 diabetes in nonobese diabetic (NOD) mice. Plos ONE. 4 (1): e4226.
Yong Zhao. (2007) New hope for diabetics: adult blood stem cells can make insulin. Discovery Medicine.7:63-67. Invited review article.
Zhao Y, Huang Z, Lazzarini P, Wang Y, Di A, Chen M. (2007) A unique human blood-derived cell population displays high potential for producing insulin. Biochem Biophys Res Commun. 360: 205-211.
Zhao Y, Huang Z, Qi M, Lazzarini P, Mazzone T. (2007) Immune regulation of T lymphocyte by a newly characterized human umbilical cord blood stem cell. Immunology Letters 108:78-87.
Zhao Y and Mazzone T. (2006) Turning "waste" into gold: Identification of novel stem cells from human umbilical cord blood. Discovery Medicine 6:87-89. Invited review article.
Zhao Y, Wang H and Mazzone T. (2006) Identification of pluripotent stem cells from umbilical cord blood with embryonic and hematopoietic characteristics. Experimental Cell Research 312: 2454-2464.
Zhao Y, Mazzone T. (2005) Human umbilical cord blood-derived f-macrophages retin pluripotentiality after thromobopoietin expansion. Experimental Cell Research310: 311-318.
Zhao Y, Glesne D, Huberman E. (2003) A human peripheral blood monocyte-derived subset acts as pluripotent stem cells as pluripotent stem cells. Proc. Natl. Acad. Sci. USA 100:2426.