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Pathobiology & Molecular Medicine

Photo of  Yigang Wang, PhD

Yigang Wang, PhD

Professor, Director of Regenerative Medicine Division

  • Medical Degree: Qinghai Medical College
  • Doctorate: Tokyo Medical and Dental University

Research/Clinical Interests

Over the past two decades, Dr. Wang's research in cardiovascular pathophysiology and therapies has focused on three areas: 1) effect of various additive agents of cardioplegic solution on functional cardiac restoration, 2) ischemic preconditioning against ischemia/reperfusion injury, its molecular mechanisms and signaling pathways, and 3) progenitor cell based cell therapy for treatment of myocardial infarction. Currently, Dr. Wang's research activities focus on stem cell therapies using three animal models. These models are myocardial infarction (MI) via ligation of the left anterior descending (LAD) coronary artery, heterotopic heart transplantation, and the use of a special cell patch to treat MI. These models are used to explore the role of progenitor cell differentiation, migration, and proliferation on protection and functional regeneration of injured heart tissue. Dr. Wang and his research team are investigating the optimal stem cell population for expressing certain cytokines (e.g., CXCR4) which can promote stem cell migration and proliferation and have the ability to attenuate the adverse remodeling process after coronary artery obstruction leading to myocardial infarction by releasing anti-fibrotic enzymes. Dr. Wang's team recently discovered that neuropeptide Y (NPY) induces the re-entry of differentiated rat neonatal and adult heart muscle cells (cardiomyocytes) into the cell cycle. His team has also recently developed a 3-dimensional (3-D) stratified cell-sheet as a potential therapeutic tissue patch, wherein inducible pluripotent (iPSC)-derived cardiac progenitor cells (cardiomyocytes and endothelial cells) and fibroblasts are co-cultured for application in the repair of ischemic heart tissue. This approach is very promising as a new therapeutic modality because it would avoid the use of synthetic biomaterial scaffolds, whose in vivo degradation by-products can produce inflammation and foreign body reactions. Dr. Wang’s team is also transducing endothelial and other progenitor cells derived from iPSC's with viral vectors encoding markers under the control of cardiomyocyte or endothelial cell-specific promoters to allow identification of cardiomyocytes, or endothelial cells. Most recently his team reported their discovery that overexpression of the micro RNA (miR-29) enhances the migration of progenitor cells from the cell patch into the subjacent myocardial infarction tissue by reducing the extracellular matrix barrier (collagen deposition) in the infarcted myocardium treated with an iPSC-based tri-cell patch applied to the epicardium. The goal of Dr. Wang's projects as a collective and unified research and discovery program is to identify and develop new strategies that enhance the application of cell-based therapies for myocardial tissue regeneration.

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Gong, Min; Yu, Bin; Wang, Jingcai; Wang, Yigang; Liu, Min; Paul, Christian; Millard, Ronald W; Xiao, De-Sheng; Ashraf, Muhammad; Xu, Meifeng 2017. Mesenchymal stem cells release exosomes that transfer miRNAs to endothelial cells and promote angiogenesis. Oncotarget, 8 28, 45200-45212

Liang, Jialiang; Huang, Wei; Cai, Wenfeng; Wang, Lei; Guo, Linlin; Paul, Christian; Yu, Xi-Yong; Wang, Yigang 2017. Inhibition of microRNA-495 Enhances Therapeutic Angiogenesis of Human Induced Pluripotent Stem Cells. Stem cells (Dayton, Ohio), 35 2, 337-350

Ma, Ruilian; Liang, Jialiang; Huang, Wei; Guo, Linlin; Cai, Wenfeng; Wang, Lei; Paul, Christian; Yang, Huang-Tian; Kim, Ha Won; Wang, Yigang 2017. Electrical Stimulation Enhances Cardiac Differentiation of Human Induced Pluripotent Stem Cells for Myocardial Infarction Therapy. Antioxidants & redox signaling, ,

Sontake, Vishwaraj; Wang, Yunguan; Kasam, Rajesh K; Sinner, Debora; Reddy, Geereddy B; Naren, Anjaparavanda P; McCormack, Francis X; White, Eric S; Jegga, Anil G; Madala, Satish K 2017. Hsp90 regulation of fibroblast activation in pulmonary fibrosis. JCI insight, 2 4, e91454

Wu, Shi-Zheng; Li, Ying-Lan; Huang, Wei; Cai, Wen-Feng; Liang, Jialiang; Paul, Christian; Jiang, Lin; Wu, Zhi-Chao; Xu, Meifeng; Zhu, Ping; Wang, Yigang 2017. Paracrine effect of CXCR4-overexpressing mesenchymal stem cells on ischemic heart injury. Cell biochemistry and function, 35 2, 113-123

Cai, Wen-Feng; Huang, Wei; Wang, Lei; Wang, Jia-Peng; Zhang, Lu; Ashraf, Muhammad; Wu, Shizheng; Wang, Yigang 2016. Induced Pluripotent Stem Cells derived Muscle Progenitors Effectively Mitigate Muscular Dystrophy through Restoring the Dystrophin Distribution. Journal of stem cell research & therapy, 6 10,

Cai, Wen-Feng; Liu, Guan-Sheng; Wang, Lei; Paul, Christian; Wen, Zhi-Li; Wang, Yigang 2016. Repair Injured Heart by Regulating Cardiac Regenerative Signals. Stem cells international, 2016 , 6193419

Cai, Wen-Feng; Wang, Lei; Liu, Guan-Sheng; Zhu, Pin; Paul, Christian; Wang, Yigang 2016. Manipulating the Hippo-Yap signal cascade in stem cells for heart regeneration. Annals of palliative medicine, 5 2, 125-34

Kondo, Hideyuki; Kim, Ha Won; Wang, Lei; Okada, Motoi; Paul, Christian; Millard, Ronald W; Wang, Yigang 2016. Blockade of senescence-associated microRNA-195 in aged skeletal muscle cells facilitates reprogramming to produce induced pluripotent stem cells. Aging cell, 15 1, 56-66

Okada, Motoi; Kim, Ha Won; Matsu-ura, Kaoru; Wang, Yi-Gang; Xu, Meifeng; Ashraf, Muhammad 2016. Abrogation of Age-Induced MicroRNA-195 Rejuvenates the Senescent Mesenchymal Stem Cells by Reactivating Telomerase. Stem cells (Dayton, Ohio), 34 1, 148-59

Wang, Yi-Gang; Huang, Pan-Pan; Zhang, Rong; Ma, Bu-Yun; Zhou, Xiu-Mei; Sun, Yan-Fang 2016. Targeting adeno-associated virus and adenoviral gene therapy for hepatocellular carcinoma. World journal of gastroenterology, 22 1, 326-37

Yu, Bin; Yang, Yueting; Liu, Huan; Gong, Min; Millard, Ronald W; Wang, Yi-Gang; Ashraf, Muhammad; Xu, Meifeng 2016. Clusterin/Akt Up-Regulation Is Critical for GATA-4 Mediated Cytoprotection of Mesenchymal Stem Cells against Ischemia Injury. PloS one, 11 3, e0151542

Cai, Wen-Feng; Kang, Kai; Huang, Wei; Liang, Jia-Liang; Feng, Yu-Liang; Liu, Guan-Sheng; Chang, De-Hua; Wen, Zhi-Li; Paul, Christian; Xu, Meifeng; Millard, Ronald W; Wang, Yigang 2015. CXCR4 attenuates cardiomyocytes mitochondrial dysfunction to resist ischaemia-reperfusion injury. Journal of cellular and molecular medicine, 19 8, 1825-35

Kang, Kai; Ma, Ruilian; Cai, Wenfeng; Huang, Wei; Paul, Christian; Liang, Jialiang; Wang, Yuhua; Zhao, Tiejun; Kim, Ha Won; Xu, Meifeng; Millard, Ronald W; Wen, Zhili; Wang, Yigang 2015. Exosomes Secreted from CXCR4 Overexpressing Mesenchymal Stem Cells Promote Cardioprotection via Akt Signaling Pathway following Myocardial Infarction. Stem cells international, 2015 , 659890

Li, Longhu; Zhao, Dong; Jin, Zhe; Zhang, Jian; Paul, Christian; Wang, Yigang 2015. Phosphodiesterase 5a Inhibition with Adenoviral Short Hairpin RNA Benefits Infarcted Heart Partially through Activation of Akt Signaling Pathway and Reduction of Inflammatory Cytokines. PloS one, 10 12, e0145766

Yu, Bin; Kim, Ha Won; Gong, Min; Wang, Jingcai; Millard, Ronald W; Wang, Yigang; Ashraf, Muhammad; Xu, Meifeng 2015. Exosomes secreted from GATA-4 overexpressing mesenchymal stem cells serve as a reservoir of anti-apoptotic microRNAs for cardioprotection. International journal of cardiology, 182 , 349-60

Chang, Dehua; Wen, Zhili; Wang, Yuhua; Cai, Wenfeng; Wani, Mashhood; Paul, Christian; Okano, Teruo; Millard, Ronald W; Wang, Yigang 2014. Ultrastructural features of ischemic tissue following application of a bio-membrane based progenitor cardiomyocyte patch for myocardial infarction repair. PloS one, 9 10, e107296

DeNicola, Megan; Du, Jianfeng; Wang, Zhengke; Yano, Naohiro; Zhang, Ling; Wang, Yigang; Qin, Gangjian; Zhuang, Shougang; Zhao, Ting C 2014. Stimulation of glucagon-like peptide-1 receptor through exendin-4 preserves myocardial performance and prevents cardiac remodeling in infarcted myocardium. American journal of physiology. Endocrinology and metabolism, 307 8, E630-43

Fan, Zhi-ying; Wang, Yi; Dong, Qi-rong; Chen, Ming; Jin, Zhi-gao; Wang, Yi-gang 2014. Lateral patellar translation effects after arthroscopic partial meniscectomy of torn discoid lateral meniscus. Orthopaedic surgery, 6 1, 38-41

Feng, Yuliang; Huang, Wei; Meng, Wei; Jegga, Anil G; Wang, Yigang; Cai, Wenfeng; Kim, Ha Won; Pasha, Zeeshan; Wen, Zhili; Rao, Fang; Modi, Rohan M; Yu, Xiyong; Ashraf, Muhammad 2014. Heat shock improves Sca-1+ stem cell survival and directs ischemic cardiomyocytes toward a prosurvival phenotype via exosomal transfer: a critical role for HSF1/miR-34a/HSP70 pathway. Stem cells (Dayton, Ohio), 32 2, 462-72

Gao, Ling; Zheng, Yan-Jun; Gu, Shan-Shan; Tan, Ji-Liang; Paul, Christian; Wang, Yi-Gang; Yang, Huang-Tian 2014. Degradation of cardiac myosin light chain kinase by matrix metalloproteinase-2 contributes to myocardial contractile dysfunction during ischemia/reperfusion. Journal of molecular and cellular cardiology, 77 , 102-12

Sheikh, Abdul Q; Kuesel, Courtney; Taghian, Toloo; Hurley, Jennifer R; Huang, Wei; Wang, Yigang; Hinton, Robert B; Narmoneva, Daria A 2014. Angiogenic microenvironment augments impaired endothelial responses under diabetic conditions. American journal of physiology. Cell physiology, 306 8, C768-78

Wang, Xiaohong; Huang, Wei; Liu, Guansheng; Cai, Wenfeng; Millard, Ronald W; Wang, Yigang; Chang, Jiang; Peng, Tianqing; Fan, Guo-Chang 2014. Cardiomyocytes mediate anti-angiogenesis in type 2 diabetic rats through the exosomal transfer of miR-320 into endothelial cells. Journal of molecular and cellular cardiology, 74 , 139-50

Wang, Yuhua; Huang, Wei; Liang, Jialiang; Wen, Zhili; Chang, Dehua; Kang, Kai; Wang, Jiapeng; Xu, Meifeng; Millard, Ronald W; Wang, Yigang 2014. Suicide gene-mediated sequencing ablation revealed the potential therapeutic mechanism of induced pluripotent stem cell-derived cardiovascular cell patch post-myocardial infarction. Antioxidants & redox signaling, 21 16, 2177-91

Wang, Yun; Wang, Yi-Gang; Ma, Teng-Fei; Li, Mei; Gu, Shu-Ling 2014. Dynamic metabolites profile of cerebral ischemia/reperfusion revealed by (1)H NMR-based metabolomics contributes to potential biomarkers. International journal of clinical and experimental pathology, 7 7, 4067-75

Wen, Zhili; Huang, Wei; Feng, Yuliang; Cai, Wenfeng; Wang, Yuhua; Wang, Xiaohong; Liang, Jialiang; Wani, Mashhood; Chen, Jing; Zhu, Pin; Chen, Ji-Mei; Millard, Ronald W; Fan, Guo-Chang; Wang, Yigang 2014. MicroRNA-377 regulates mesenchymal stem cell-induced angiogenesis in ischemic hearts by targeting VEGF. PloS one, 9 9, e104666

Gong, Min; Yu, Bin; Wang, Yi-Gang; Xu, Meifeng 2013. Bone marrow rejuvenation. An excellent potential therapy for age-related endothelial dysfunction. Circulation journal : official journal of the Japanese Circulation Society, 77 12, 2886-8

Huang, Wei; Dai, Bo; Wen, Zhili; Millard, Ronald W; Yu, Xi-Yong; Luther, Kristin; Xu, Meifeng; Zhao, Ting C; Yang, Huang-Tian; Qi, Zhihua; Lasance, Kathleen; Ashraf, Muhammad; Wang, Yigang 2013. Molecular strategy to reduce in vivo collagen barrier promotes entry of NCX1 positive inducible pluripotent stem cells (iPSC(NCX¹?)) into ischemic (or injured) myocardium. PloS one, 8 8, e70023

Lei, Wen; Liu, Hong-bin; Wang, Shi-bing; Zhou, Xiu-mei; Zheng, Shui-di; Guo, Ke-ni; Ma, Bu-yun; Xia, Yu-long; Tan, Wen-song; Liu, Xin-yuan; Wang, Yi-gang 2013. Tumor suppressor in lung cancer-1 (TSLC1) mediated by dual-regulated oncolytic adenovirus exerts specific antitumor actions in a mouse model. Acta pharmacologica Sinica, 34 4, 531-40

Wang, Yun; Ma, Tengfei; Zhou, Li; Li, Mei; Sun, Xiao-Jing; Wang, Yi-Gang; Gu, Shuling 2013. Penehyclidine hydrochloride protects against oxygen and glucose deprivation injury by modulating amino acid neurotransmitters release. Neurological research, 35 10, 1022-8

Yu, Bin; Gong, Min; He, Zhisong; Wang, Yi-Gang; Millard, Ronald W; Ashraf, Muhammad; Xu, Meifeng 2013. Enhanced mesenchymal stem cell survival induced by GATA-4 overexpression is partially mediated by regulation of the miR-15 family. The international journal of biochemistry & cell biology, 45 12, 2724-35

Yu, Bin; Gong, Min; Wang, Yigang; Millard, Ronald W; Pasha, Zeeshan; Yang, Yueting; Ashraf, Muhammad; Xu, Meifeng 2013. Cardiomyocyte protection by GATA-4 gene engineered mesenchymal stem cells is partially mediated by translocation of miR-221 in microvesicles. PloS one, 8 8, e73304

Liang, Jialiang; Huang, Wei; Yu, Xiyong; Ashraf, Atif; Wary, Kishore K; Xu, Meifeng; Millard, Ronald W; Ashraf, Muhammad; Wang, Yigang 2012. Suicide gene reveals the myocardial neovascularization role of mesenchymal stem cells overexpressing CXCR4 (MSC(CXCR4)). PloS one, 7 9, e46158

Sheikh, Abdul Q; Hurley, Jennifer R; Huang, Wei; Taghian, Toloo; Kogan, Andrei; Cho, Hongkwan; Wang, Yigang; Narmoneva, Daria A 2012. Diabetes alters intracellular calcium transients in cardiac endothelial cells. PloS one, 7 5, e36840

Wang, Shi-Bing; Tan, Yuan; Lei, Wen; Wang, Yi-Gang; Zhou, Xiu-Mei; Jia, Xiao-Yuan; Zhang, Kang-Jian; Chu, Liang; Liu, Xin-Yuan; Qian, Wen-Bin 2012. Complete eradication of xenograft hepatoma by oncolytic adenovirus ZD55 harboring TRAIL-IETD-Smac gene with broad antitumor effect. Human gene therapy, 23 9, 992-1002

Dai, B., Huang, W., Xu, M., Millard, R.W., Gao, M.H., Hammond, H.K., Menick, D.R., Ashraf, M., & Wang, Y. 2011. Reduced Collagen Deposition in Infarcted Myocardium Facilitates Induced Pluripotent Stem Cells (iPSC) Engraftment and Angiomyogenesis for Improvement of Left Ventricular Function Journal of the American College of Cardiology (JACC), ,

Huang, W., Wang, T., Zhang, D., Zhao, T., Dai, B., Ashraf, A., Wang, X., Xu, M., Millard, R.W., Fan, G.C., Ashraf, M., Yu, X.Y., & Wang, Y. 2011. Mesenchymal Stem Cells Overexpressing CXCR4 Attenuate Remodeling of Post-myocardial Infarction by Releasing Matrix Metalloproteinase-9 Stem Cell and Development. Stem Cells Dev, ,

Qian J, Vafiadaki E, Florea SM, Singh VP, Song W, Kung Lam C, Wang Y, Yuan Q, Pritchard TJ, Cai W, Haghighi K, Rodriguez P, Wang HS, Sanoudou D, Fan GC, Kranias EG 2011. Small Heat Shock Protein 20 Interacts With Protein Phosphatase-1 and Enhances Sarcoplasmic Reticulum Calcium Cycling Circ Res., 10, 108 12, 1429-38

Huang, W., Zhang, D., Millard, R.W., Wang, T., Zhao, T., Fan, G.C., Ashraf, A., Xu, M., Ashraf, M., & Wang, Y. 2010. Gene manipulated peritoneal cell patch repairs infarcted myocardium J Mol Cell Cardiol, 48 4, 702-12

Huang, Wei; Zhang, Dongsheng; Millard, Ronald W; Wang, Tao; Zhao, Tiemin; Fan, Guo-Chang; Ashraf, Atif; Xu, Meifeng; Ashraf, Muhammad; Wang, Yigang 2010. Gene manipulated peritoneal cell patch repairs infarcted myocardium. Journal of molecular and cellular cardiology, 48 4, 702-12

Wang Y, Zhang D, Ashraf M, Zhao T, Huang W, Ashraf A, Balasubramaniam A 2010. Combining neuropeptide Y and mesenchymal stem cells reverses remodeling after myocardial infarction. Am J Physiol Heart Circ Physiol., 298 1, H275-86

Zhang D, Huang W, Dai B, Zhao T, Ashraf A, Millard RW, Ashraf M, Wang Y 2010. Genetic manipulated progenitor cell sheet with diprotin A improves myocardial function and repair of infarcted hearts Am J Physiol Heart Circ Physiol, 299 5, H1339-47

Zhang X, Wang X, Zhu H, Zhu C, Wang Y, Pu WT, Jegga AG, Fan GC 2010. Synergistic effects of the GATA-4-mediated miR-144/451 cluster in protection against simulated ischemia/reperfusion-induced cardiomyocyte death. J Mol Cell Cardiol, 49 5, 841-50

Ahmad, N., Wang, Y., Ali, A.K., & Ashraf, M. 2009. Long-acting phosphodiesterase-5 inhibitor, tadalafil, induces sustained cardioprotection against lethal ischemic injury Am J Physiol Heart Circ Physiol, 297 , H387-91

Jagatheesan, Ganapathy; Rajan, Sudarsan; Schulz, Emily M; Ahmed, Rafeeq P H; Petrashevskaya, Natalia; Schwartz, Arnold; Boivin, Greg P; Arteaga, Grace M; Wang, Tao; Wang, Yi-Gang; Ashraf, Muhammad; Liggett, Stephen B; Lorenz, John; Solaro, R John; Wieczorek, David F 2009. An internal domain of beta-tropomyosin increases myofilament Ca(2+) sensitivity. American journal of physiology. Heart and circulatory physiology, 297 1, H181-90

Millard, R.W., & Wang, Y. 2009. Milieu Inte´rieur: The search for myocardial arteriogenic signals Journal of the American College of Cardiology, 53 23, 2148-9

Wang, X., Zhao, T., Huang, W., Wang, T., Qian, J., Xu, M., Kranias, E.G., Wang, Y., & Fan, G.C. 2009. Hsp20-Engineered Mesenchymal Stem Cells Are Resistant to Oxidative Stress via Enhanced Activation of Akt and Increased Secretion of Growth Factors Stem Cells, 27 12, 3021-31

Wang, X., Zingarelli, B., Connor, M.O., Zhang, P., Adeyemo, A., Kranias, E.G., Wang, Y., & Fan, G.C. 2009. Overexpression of Hsp20 Prevents Endotoxin-Induced Myocardial Dysfunction and Apoptosis via Inhibition of NF-κB Activation JMCC, 47 3, 382-90

Zhao, T., Zhang, D., Millard, R.W., Ashraf, M., & Wang, Y. 2009. Stem cell homing and angiomyogenesis in transplanted hearts are enhanced by combined intramyocardial SDF-1 delivery and endogenous cytokine signaling Am J Physiol Heart Circ Physiol, 296 4, H976-86

Pasha, Z., Wang, Y., Sheikh, R., Zhang, D., Zhao, T., & Ashraf, M. 2008. Preconditioning Enhances Cell Survival and Differentiation of Stem Cells during Transplantation in Infarcted Myocardium Cardiovas Res, 77 , 134-42

Prasad, V., Bodi, I., Meyer, J.W., Wang, Y., Ashraf, M., Engle, S.J., Doetschman, T., Sisco, K., Nieman, M.L., Miller, M.L., Lorenz, J.N., & Shull, G.E. 2008. Impaired cardiac contractility in mice lacking both the AE3 Cl-/HCO3- exchanger and the NKCC1 Na+-K+-2Cl- cotransporter: Effects on Ca2+ handling and protein phosphatases J Biol Chem, 283 46, 31303-14

Zhang, D., Fan, G.C., Zhou, X., Zhao, T., Pasha, Z., Xu, M., Zhu, Y., Ashraf, M., & Wang Y. 2008. Over-expression of CXCR4 on mesenchymal stem cells augments myoangiogenesis in the infarcted myocardium JMCC, 44 2, 281-92

Wang, Y., Ahmad, N., Wang, B., & Ashraf, M. 2007. Chronic Preconditioning: A Novel Approach For Cardiac Protection Am J Physiol Heart Circ Physiol, 292 5, H2300-2305

Fan, G.C., Yuan, Q., Song, G., Wang, Y., Chen, G., Qian, J., Zhou, X., Lee, Y.J., Ashraf, M., & Kranias, E.G 2006. Small Heat-Shock Protein Hsp20 Attenuates {beta}-Agonist-Mediated Cardiac Remodeling Through Apoptosis Signal-Regulating Kinase 1 Circ Res, 99 11, 1233-42

Wang, Y., Haider, H.K., Ahmad, N., Xu, M., Ge, R., & Ashraf M 2006. Combining pharmacological mobilization with intramyocardial delivery of bone marrow cells over-expressing VEGF is more effective for cardiac repair JMCC, 40 , 736-745

Wang, Y., Haider, H.K., Ahmad, N., Zhang, D., & Ashraf, M. 2006. Evidence for Ischemia Induced Host Derived Bone Marrow Cell Mobilization into Cardiac Allografts J Mol Cell Cardiol, 41 3, 478-487