Jiemei Wang, PhD

Education

Ph.D., Sun Yat-Sen University (China), 2009

Research Focus

Endothelial dysfunction, microRNA regulatory network in tissue repair and regeneration, endoplasmic reticulum and oxidative stress in metabolic disorders.

The goal of my study is to translate the mechanistic insights for new therapeutic modalities in cardiovascular disorders and tissue repair. There are two major focuses in my research:

1. microRNA regulation of tissue regeneration: MicroRNAs are newly discovered short oligonucleotides that act as key regulators of gene expression. It is until recently that the importance of microRNA-directed gene regulation in vascular disorders has been recognized. Up to date, little information exists regarding microRNA regulation of stem cell-mediated neovascularization. One of my research interests is to investigate the therapeutic potential of microRNA-engineered stem cells under disease condition and to explore candidate microRNAs that might serve as therapeutic targets. Previously we have found that increasing certain microRNAs could boost bone marrow derived angiogenic cells in diabetes by reducing harmful reactive oxygen species (ROS). For example, miR-27b reduced mitochondrial oxidative stress by increasing the activities of anti-oxidant enzymes, i.e. Manganese SOD (MnSOD), and decreasing pro-oxidant protein expressions, i.e. p66shc adaptor protein, etc. miR-27b also suppresses several anti-angiogenic molecules, thus boosting the function of bone marrow derived angiogenic cells in diabetes. These diabetic cells with enhanced miR-27b expression can close refractory wounds in diabetic animals and can increase tissue blood perfusion. Our on-going project is to determine the biogenesis of miRNAs and their impact on tissue repair, in response to detrimental stress, such as diabetes, hyperlipidemia, hypertension, etc. This project utilizes comprehensive approaches, including molecular, biochemical, morphological, and genetic techniques, as well as diabetic models of various unique transgenic and gene knockout animals in ex vivo and in vivo studies.

2. Endothelial injury and repair under disease setting: Vascular endothelium is not only a barrier layer that separate blood and tissue, it is considered as a vast endocrine gland that stretches over the entire vascular tree with a surface area of 400 square meters. Endothelium well-being is essential to normal vascular homeostasis. Its dysfunction is one of the first steps leading to atherosclerosis. Circulating markers of such endothelial cell damage include endothelial microparticles derived from activated or apoptotic cells. One of our study is to look at the role of EMPs as both markers and mediators in vascular injury. In a cohort study, we discovered that circulating EMPs were the only independent indicator of arterial function. We further identified BH4 (tetrahydrobiopterin) as a key substance that controls the release of EMPs in response to C reactive protein (CRP)-induced endothelial injury. Endothelial integrity depends not only on the extent of injury, but also on the endogenous capacity for repair. Endothelial progenitor cells (EPCs) are vascular endothelial cell (EC) precursors that are capable of differentiating into mature endothelial cells and producing new vessels but their functions are impaired in various cardiovascular diseases. In a clinical study, we found that modest exercise significantly increased blood EPCs. Possible mechanisms include improving the anti-inflammatory and anti-coagulant potential of EPCs by increasing shear stress. This fact sheds light on the possibility of using patient-derived EPCs for cell therapy via gene engineering preparation. We are now investigating the morphogenic activities of EPCs that might contribute to EPCs’s therapeutic potentials for wound healing.

Recent Publications

Jiang RZ, Cai JJ, Zhu ZW, Chen DD, Wang JM, Wang QD, Teng YC, Huang YJ, Tao MF, Xia AB, Xue M, Zhou SH, Chen AF. Hypoxic Trophoblast HMGB1 Induces Endothelial Cell Hyperpermeability via the TRL-4/Caveolin-1 Pathway. J Immunol 2014 (ePub ahead of Print).

Wang JM, Chen AF. MicroRNAs and endothelial progenitor cells. Chandan Sen Ed. Edition 1, Chapter 10. MicroRNA and Regenerative Medicine. Academic Press; 2014.

Wang JM, Tao J, Chen DD, Cai JJ, Wang QD, Irani K, Yuan H, Chen AF. MicroRNA miR-27b rescues bone marrow-derived angiogenic cell function and accelerates wound healing in type 2 diabetes. Arteriosclerosis, Thrombosis, and Vascular Biology. 34:99-109,2014.

Bae ON*, Wang JM*, Wang QD, Yuan H, Chen AF. Oxidative stress-mediated thrombospondin-2 upregulation impairs bone marrow-derived angiogenic cell function in diabetes. Arteriosclerosis, Thrombosis, and Vascular Biology; 33:1920-1927, 2013.

Wang JM, Isenberg JS, Billiar TR, Chen AF. Thrombospondin-1/CD36 Pathway Contributes to Bone Marrow-Derived Angiogenic Cell Dysfunction in Type 1 Diabetes via Sonic Hedgehog Pathway Suppression. American Journal of Physiology-Endocrinology and Metabolism. 305:E1464-1472, 2013.

Wang JM, Luo JD, Chen AF. Sonic Hedgehog accelerates wound healing via enhancing cutaneous nitric oxide function in diabetes. Chandan Sen Ed. Volume 2, Chapter 28. Advances in Wound Care. Mary Ann Liebert, Inc; 171-176, 2011.

Wang JM, Chen AF. Gene and cell therapy in cardiovascular disease. Dingfeng Su Ed. Volume 4. Chapter 27. Cardiovascular Pharmacology, People’s Medical Publishing House;638-662, 2011.