Xin (Sarah) Zhang, MD Assistant Professor of Medicine   Dr. Zhang's Research Group
Mailing Address: 941 Stanton L. Young Blvd., BSEB 331A Oklahoma City, OK 73104-5020	Telephone: (405) 271-5896 ext 47790 Fax: (405) 271-3973
Email: xin-zhang@ouhsc.edu

Research Interests

1. Molecular mechanisms of diabetic retinopathy and early interventions. Diabetic retinopathy is the leading cause of visual disability and blindness among adults in the US and worldwide. Early hallmarks of diabetic retinopathy include retinal vascular endothelial dysfunction, blood-retinal barrier breakdown, vascular leakage and retinal ischemia. As the pathogenic mechanisms are largely undefined, to date there is no satisfactory treatment for preventing the vision loss associated with diabetes. Our research interests are to understand the role of oxidative stress and inflammation in the pathogenesis of retinal vascular cellular dysfunction in diabetic retinopathy. Using cultured retinal cells (in vitro system) and diabetes animal models (in vivo system), we are characterizing the oxidative stress/anti-oxidative defense and inflammatory status in diabetic retina and retinal cells, particularly in retinal vascular endothelial cells, pericytes and retinal pigment epithelial cells. We are also using genetic tools, transgenic and knockout animals to study the key function of endogenous anti-inflammatory factors in diabetic retinopathy. In an ongoing study, we are attempting to elucidate how macrophages are implicated in the pathogenesis of vascular leakage and retinal neovascularization in diabetic retinopathy and other ischemic retinal diseases.
2. Role of angiogenic/anti-angiogenic factors in obesity, insulin resistance and Type 2 diabetes. Obesity, insulin resistance and Type 2 diabetes are clustered as the most important metabolic disorders, substantially increasing morbidity and impairing quality of life. Excess body fat mass, particularly visceral fat, leads to the dysregulation of the adipokines (proteins secreted from fat cells) and contributes to increased risk of cardiovascular and peripheral vascular diseases. Recent findings from us and other groups indicate that anti-angiogenic factors are associated with obesity and Type 2 diabetes. From bedside to bench, we are now investigating the functions and mechanisms of anti-angiogenic inhibitors in lipid metabolism and adiposity using cell culture system and genetic animal models. Another current study focuses on the role of angiogenic/anti-angiogenic factors in peripheral vascular diseases in diabetic and non-diabetic patients. The outcomes from these studies will provide scientific explanations for the clinical observations and have great potential to translate into clinical application by identifying new biomarkers and developing novel therapeutics. Research in our laboratory is supported by the National Institutes of Health (NIH), the Juvenile Diabetes Research Foundation International (JDRF), and the Oklahoma Center for the Advancement of Science and Technology (OCAST).

Education

Zhang, S.X., Wang, J.J., Dashiti, A., Wilson, K., Zou, M-H., Szweda, L., Ma, J-x., and Lyons, T.J. Pigment Epithelium-derived Factor (PEDF) mitigates inflammation and oxidative stress in retinal pericytes exposed to oxidized-LDL. J Mol Endocrinol, June 27, 2008 [Epub ahead of print].

Yu, Y., Jenkins, A. J., Nankervis, A. J., Hanssen, K., Scholz, H., Henriksen, T., Lorentzen, B., Garg, S.K.,  Menard, M. K., Hammad, S., Scardo, J.C., Stanley, J.R., Dashti, A., May, K., Lu, K., Aston, C. E., Zhang, S.X.,Ma, J-x., and Lyons, T. J. Anti-angiogenic factors and preeclampsia in Type 1 diabetes. Diabetologia, Submitted, 2008.

Zhang, S.X., Wang, J.J., Mott, R., Chen, Y., Knapp R.R., Cao, W. and Ma, J-x. Anti-inflammatory Effects of Pigment Epithelium-derived Factor in Diabetic Nephropathy. Am J Physiol Renal Physiol, [Epub ahead of print], 2008.

Zhang, S.X., Jenkins, A.J., Rowley, K.G., Karschimkus, C.S., Nelson, C.L., Lyons, T.J., Best, J.D. and Ma, J-x. Increased Serum PEDF is Associated With Microvascular Complications, Vascular Stiffness, and Inflammation in Type 1 Diabetes. Diabet. Med, 24: 1345-1351, 2007.

Zhang, S.X. and Ma, J-x. Ocular neovascularization: implication of endogenous angiogenic inhibitors and potential therapy. Prog Retin Eye Res, 26(1):1-37, 2007.

Zhang, S.X., Wang, J.J., Gao G, Park K, and Ma, J-x. Reciprocal regulation between pigment epithelium-derived factor (PEDF) and vascular endothelial growth factor (VEGF). J. Mol. Endocrinol., 37(1):1-12, 2006.

Sima, J., Ma, J-x, Zhang, S.X., Guo, J. Study of the influence of angiostatin intravitreal injection on vascular leakage in retina and iris of the experimental diabetic rats. Yan Ke Xue Bao. 22(4):252-8, 2006.

Tomasek, J.J., Haaksma, C.J., Schwartz, R.J., Vuong, D.T., Zhang, S.X., Ash, J.D., Ma, J-x, Al-Ubaidi, M.R. Deletion of smooth muscle α-actin alters blood-retina barrier permeability and retinal function. Invest Ophthalmol Vis Sci., 47(6):2693-2700, 2006.

Zhang, S.X., Wang, J.J., Mott, R., Knapp, R.R., Cao, W., Lau, K. and Ma, J-x. Salutary Effect of Pigment Epithelium-Derived Factor in Diabetic Nephropathy: Evidence for Anti-fibrogenic Activities. Diabetes, 55(6):1678-1685, 2006.

Liu, L., Yu, Q., Wang, H., Zhang, S.X., Huang, C., and Chen, X. Association of Intercellular Adhesion Molecule 1 Polymorphisms with Retinopathy in Chinese Patients with Type 2 Diabetes. Diabet. Med., 23: 643-648, 2006.

Zhang, S.X., Wang, J.J., Lu, K., Mott, R., and Ma, J-x. Therapeutic Potential of Angiostatin in Diabetic Nephropathy. J. Am. Soc. Nephro., 17(2):475-486, 2006.

Zhang, S.X., Wang, J.J., Lu, K., Mott, R., and Ma, J-x. Pigment Epithelium-derived Factor (PEDF) Is A Novel Endogenous Anti-inflammatory Factor. FASEB J., 20(2):323-325, 2006.

Zhang, S.X., Ma, J-x., Sima, J., Ottlecz, A., Hu, M., Lambrou, G.N. Genetic Difference in Susceptibility to the Blood-retina Barrier Breakdown in Diabetes and Oxygen-induced Retinopathy. Am.J.Pathol., 166: 313-321, 2005.

Zhang, S.X., Sima, J., Wang, J.J., Shao, C., Fant, J. and Ma, J-x.  Systemic and periocular delivery of plaseminogen kringle 5 reduces vascular leakage in rat models of oxygen-induced retinopathy and diabetes.  Curr. Eye Res., 30:681-689, 2005.

Zhang, S.X., Wang, J., , Lu, K., Chen, Y., Mott, R., Sato, S. and Ma, J-x. Decreased Expression of Pigment Epithelium-derived Factor Is Involved in the Pathogenesis of Diabetic Nephropathy. Diabetes, 54: 243-250, 2005.

Reviews and Invited Papers

Zhang, S.X. and Ma, J-X. Ocular Neovascularization: Implication of Endogenous Angiogenic Inhibitors and Potential Therapy. Prog Retin Eye Res, 26(1):1-37, 2007.

Ma, Jx, Zhang, S.X., Wang, J.J.  Down-regulation of Angiogenic Inhibitors: A New  Pathogenic Mechanism For Diabetic Complications. Invited Review Curr Diabetes Rev. 1, 183-196, 2005.

Books Chapters and Manuscripts

Ma, J-X., Zhang, S.X. Endogenous Angiogenic Inhibitors in Diabetic Retinopathy. in "Ocular Angiogenesis:  Diseases, Mechanisms and Therapeutics" Eds J. Tombran-Tink and C.J. Barnstable, Humana Press, Totowa, NJ. 2006, pp 23-44.