Integrative and Translational Research: stroke; hypertension; stem cell; diabetic complications; cellular microvesicles (MVs) and exosomes; cancer.
Approaches: Contemporary techniques cutting-edge methodologies are used for my studies at molecular, cellular and in vivo levels, such as telemetric cardiovascular monitoring, behavior analysis, brain microinjection, cell transplantation, real-time RT-PCR, gene transfection, RNA interference (RNAi), nanoparticle tracking analysis (NTA), mass spectral (ms), mRNA/microRNA deep sequencing (RNAseq), ELISA, western blot, etc.
Summary of My Research Emphasis
- Study of the role of renin-angiotensin system (RAS) in cardiovascular disease. We are currently focusing on the two counteracting RAS signaling pathways (Ang II/AT1 and Ang1-7/Mas). Gene modified mice models (transgenic or gene deletion) are used for the studies. Middle cerebral artery occlusion (MCAO) is conducted for introducing focal ischemic stroke on animals. The long-term objective is to understand the roles of different RAS pathways in regulating endothelial progenitors (EPCs), endothelial cell (ECs), smooth muscle cells (SMCs), neuronal and glial function. The blood-brain barrier (BBB) and bone marrow(BM) mechanisms are also explored.
- Study of stem cell-based and gene-based therapeutic avenues for stroke and tissue injury.The BM derived EPCs may play an important role in tissue repair. The interest in my laboratory is to understand the changes of EPCs function in hypertension and type-2 diabetes. We hypothesize that the local RAS, the stromal derived factor (SDF-1a) and its receptor CXCR4 may regulate the EPCs function such as generation, mobilization and homing for angiogenesis and repair. We are interested in transplantation (or in situ reprogram for regeneration) of EPCs and neuron progenitor cells (NPCs) for treating ischemic stroke.
- Study of extracellular microvesicles (MVs) and Exosomes in four major areas: 1) release, isolation, purification and detection; 2) contents, modulation and function; 3) biomarkers; 4) targets for therapeutics. Accumulating evidence indicate that extracellular MVs and exosomes could be biomarkers and therapeutic targets of various diseases. The long-term objective in my laboratory is to understand the roles and mechanisms of extracellular MVs and exosomes mediated cell-cell communication in physiology and pathologies (cardiovascular and neurological diseases, cancers).
M.D. Nanhua University Medical College
Ph.D. Beijing University Medical Center
Postdoctoral Wright State University Boonshoft School of Medicine
Peer Reviewed Articles (selected publications, * Corresponding author)
1). Wu K, Yang Y, Zhong Y, Ammar HM, Zhang P, Guo R, Liu H, Cheng C, Koroscil TM, Chen Y, Liu S, Bihl JC. The effects of microvesicles on endothelial progenitor cells are compromised in type 2 diabetic patients via downregulation of miR-126/VEGFR2 pathway. Am J Physiol Endocrinol Metab. 2016;310(10):E828-37.
2). Ma CL, Ma XT, Wang JJ, Liu H, Chen YF, Yang Y. Physical exercise induces hippocampal neurogenesis and prevents cognitive decline. Behav Brain Res. 2016;317:332-339
3). Jinju Wang, Yun Zhong, Xiaotang Ma, Xiang Xiao, Chuanfang Cheng, Yusen Chen, Ifeanyi Iwuchukwu, Kenneth J. Gaines, Bin Zhao, Shiming Liu, Jeffrey B. Travers, Ji C. Bihl*, Yanfang Chen*. Analyses of endothelial cells and endothelial progenitor cells released microvesicles by using microbead and Q-dot based nanoparticle tracking analysis. Scientific Reports 2016, 20;6:24679.
4). Yang Y, Yang X, Dong Y, Chen N, Xiao X, Liu H, Li Z, Chen Y*.Transcutaneous electrical acupoint stimulation alleviates adverse cardiac remodeling induced by overload training in rats. J Appl Physiol. 2016;120(11):1269-76.
5). Wang J, Guo R, Yang Y, Jacobs B, Chen S, Iwuchukwu I, Gaines K, Chen Y, Simman R, Lv G, Wu K, Bihl J. The Novel methods for analysis of exosomes released from endothelial cells and endothelial progenitor cells. Stem Cell International. 2016:2639728.
6). Bihl JC, Rapp CM, Chen Y, Travers JB. UVB generates microvesicle particle release in part due to platelet-activating factor signaling. Photochem Photobiol 2016;92(3):503-6.
7). Wang J, Chen Y, Yang Y, Xiao X, Chen S, Zhang C, Jacobs B, Zhao B, Bihl J*, Chen Y*. Endothelial progenitor cells and neural progenitor cells synergistically protect cerebral endothelial cells from hypoxia/reoxygenation-induced injury via activating the PI3k/Akt pathway. Mol Brain 2016; 9(1):12
8). Bihl JC*, Zhang C, Zhao Y, Xiao X, Ma X, Chen Y, Chen S, Zhao B, Chen Y*. Angiotensin-(1-7) counteracts the effects of Ang II on vascular smooth muscle cells, vascular emodeling and hemorrhagic stroke: role of the NFкB inflammatory pathway. Vascul Pharmacol. 2015;73:115-23.
9). Yusen Chen, Yun Xiao, Zhijun Lin, Xiang Xiao, Caixia He, Ji C. Bihl, Bin Zhao, Xiaotang Ma, Yanfang Chen*. The role of circulating platelets microparticles and platelet parameters in acute ischemic stroke patients. Journal of Stroke and Cerebrovascular Diseases 2015; 24(10):2313-20.
10). Xiang Xiao, Cheng Zhang, Xiaotang Ma, Huilai Miao, Jinju Wang, Langni Liu, Shuzhen Chen, Rong Zeng, Yanfang Chen*, Ji C Bihl. Angiotensin-(1-7) counteracts angiotensin II-induced dysfunction in cerebral endothelial cells via modulating Nox2/ROS and PI3K/NO pathways. Experimental Cell Research 2015;336(1):58-65.
11). Xiang Xiao, Xiake Bi, Yingxia Liu, Ray Fan, Xiaotang Ma, Jinju Wang, Bin Zhao, Yanfang Chen*, Ji Chen. Cellular membrane microparticles: potential targets of combinational therapy for vascular disease. Curr Vasc Pharmacol. 2015;13(4):449-58.
12). Yusen Chen, Bing Lu, Jinju Wang, Shuzhen Chen, Zhijun Lin, Xiaotang Ma; Yajing Liu; Bin Zhao, Yanfang Chen*. Circulating CD133+ CD34+ progenitor cells and plasma stromal-derived factor-1 alpha: predictive role in ischemic stroke patients. Journal of Stroke and Cerebrovascular Diseases 2015;24(2):319-26
13). Jiyu Wen, Xiaojun Wen, Jinju Wang, Yang Shu, Zhidong Qiu, Zhongkao Liu, Ran Li, Guofang Zeng, Shiting Bao, Huilai Miao, Yanfang Chen*, and Mingyi Li. Anti-cancer effects of glypican-3 on Huh-7 hepatocellular carcinoma cells. J Cell Sci Ther 2014;5: 186
14). Dan Yi, Ji Chen, Machenzie S Newman, Yanfang Chen*, Richard Simman. The Preliminary study of effects of tolfenamic acid on cell proliferation, cell apoptosis, and intracellular collagen deposition in Keloid fibroblasts in vitro. Dermatology Research and Practice 2014 2014;2014:736957
15). Jian-ying Chen, An Ran, Jin-ju Wang, Shu-zhen Chen, Zhen-jun Liu, Mian-ming Hong, Jing-hu Liu, Meng-yuan Xiao, Yan-fang Chen*. Effects of mesenchymal stem cell-derived microvesicles on treating pulmonary arterial hypertension. Acta Pharmacologica Sinica 2014; 35(9):1121-8
16). Wang YK, Shen D, Hao Q, Yu Q, Wu ZT, Deng Y, Chen YF, Yuan WJ, Hu QK, Su DF, Wang WZ. Overexpression of angiotensin-converting enzyme 2 attenuates tonically active glutamatergic input to the rostral ventrolateral medulla in hypertensive rats. Am J Physiol Heart Circ Physiol 2014;307: H182–H190
17). Jiaoling Zheng, Guangze Li, Shuzhen Chen, Ji Chen, Joshua Buck, Yulan Zhu; Huijing Xia, Eric Lazartigues, Yanfang Chen*, James E. Olson. Activation of the ACE2/Ang-(1-7)/Mas pathway reduces oxygen-glucose deprivation induced tissue swelling, ROS production, and cell death in mouse brain with angiotensin II overproduction. Neurosciences 2014; 273 (2014) 39–51
18). Gu S, Zhang W, Chen J, Ma R, Xiao X, Ma X, Yao Z, Chen Y*. EPC-derived microvesicles protect cardiomyocytes from Ang II-induced hypertrophy and apoptosis. PloS ONE 2014; 9(1):e85396
19). Chen J, Zhao Y, Chen S, Wang J, Xiao X, Ma X, Penchikala M, Xia H, Lazartigues E, Zhao B, Chen Y*. Neuronal over-expression of ACE2 protects brain from ischemia-induced damage. Neuropharmacology 2014; 79:550–558
20). Zheng JL, Li GZ, Chen SZ, Wang JJ, Olson JE, Xia HJ, Lazartigues E, Zhu YL, Chen YF*. Angiotensin converting enzyme 2/Ang-(1-7)/Mas axis protects brain from ischemic injury with a tendency of age-dependence. CNS Neurosci Ther. 2014; 20(5):452-9
21). Chen J, Xiao X, Chen S, Zhang C, Chen J, Yi D, Shenoy V, Raizada MK, Zhao B, Chen Y*. Angiotensin converting enzyme 2 priming enhances the function of endothelial progenitor cells and their therapeutic efficacy. Hypertension 2013;61(3):681-9
22). Li Y, Liao F, Yin XJ, Cui LL, Ma GD, Nong XX, Zhou HH, Chen YF, Zhao B, Li KS. An association study on ADAM10 promoter polymorphisms and atherosclerotic cerebral infarction in a Chinese population. CNS Neurosci Ther. 2013; 19(10):785-94
23). Zhao YH, Yuan B, Chen J, Feng DH, Zhao B, Qin C, Chen YF*. Endothelial progenitor cells: therapeutic perspective for ischemic stroke. CNS Neurosci Ther. 2013;19(2): 67–75
24). Zhu J, Chen S, Wang J, Zhang C, Zhang W, Liu P, Ma R, Chen Y*, Yao Z. Splenectomy increases the survival time of heart allograft via developing immune tolerance. J Cardiothorac Surg. 2013;8(1):129
25). Wang J, Chen S, Ma X, Cheng C, Xiao X, Chen J, Liu S, Zhao B, Chen Y*. Effects of endothelial progenitor cell-derived microvesicles on hypoxia-reoxygenation induced endothelial dysfunction and apoptosis. Oxidative Medicine and Cellular Longevity 2013;2013:572729
26). Ma X, Zhang H, Pan Q, Zhao Y, Chen J, Zhao B, Chen Y*. Hypoxia/Aglycemia-induced endothelial barrier dysfunction and tight junction protein downregulation can be ameliorated by citicoline. PloS ONE 2013;8(12):e82604
27). Zhu P, Chen JM, Guo HM, Fan XP, Zhang XS, Fan RX, Zheng SY, Wu RB, Xiao XJ, Huang HL, Zhu XL, Liu HP, Long G, Chen Y, Zhang J. Matrine inhibits disturbed flow-enhanced migration via down-regulation of ERK1/2-MLCK signaling vascular smooth muscle cells. Ann Vasc Surg. 2012;26(2):268-75
28). Mao S, Garzon-Muvdi T, Difulvio M, Chen Y, Delpire E, Alvarez FJ, Alvarez-Leefmans FJ. Molecular and functional expression of cation-coupled chloridecotranspoters in rodent doral root ganglion neurons during postnatal maturation. J Neurophysiol. 2012;108(3):834-52
29). Gu X, Lu Y, Chen J, He H, Li P, Yang T, Li L, Liu G, Chen Y*, Zhang L. Mechanisms mediating propofol protection of pulmonary epithelial cells against lipopolysaccharide-induced cell death. Clin Exp Pharmacol Physiol. 2012;39(5):447-53
30). Chen J, Liu YM, Tang YX, Chen J, Hu XQ, Liu N, Wang SX, Zhang Y, Zeng WG, Ni HJ, Zhao B, Chen YF*, Tang ZP. Transplantation of adipose-derived stem cells is associated with neural differentiation and functional improvement in a rat model of intracerebral hemorrhage. CNS Neurosci Ther. 2012;18(10):847-54
31). Wang J, Chen S, Zhang C, Stegeman S, Pfaff-Amesse T, Zhang Y, Zhang W, Amesse L, Chen Y*. Human endometrial stromal stem cells differentiate into megakaryocytes with the ability to produce functional platelets. PLoS ONE 2012;7(8): e44300
32). Chen J, Chen J, Chen S, Zhang C, Zhang L, Xiao X, Das A, Zhao Y, Yuan B, Morris M, Zhao B, Chen Y*. Transfusion of CXCR4-primed endothelial progenitor cells reduces cerebral ischemic damage and promotes repair in db/db diabetic mice. PLoS ONE 2012;7(11): e50105
33). Zhu P, Wen YG, Fan XP, Zhou ZL, Fan RX, Chen JM, Huang KL, Zhu XL, Chen Y, Zhuang J. A rapid and sensitive liquid chromatography-tendem mass spectrometry method for determination of olopatadine concentration in human plasma. J Anal Toxicol. 2011; 35:113-8
34). Chen J, Chen S, Chen Y, Zhang C, Wang J, Zhang W, Liu G, Zhao B, Chen Y*. Circulating endothelial progenitor cells and cellular membrane microparticles in db/db diabetic mouse: possible implications in cerebral ischemic damage. Am J Physiol Endocrinol Metab 2011; 301:E62-E71
35). Northcott CA1, Watts S, Chen Y, Morris M, Chen A, Haywood JR. Adenoviral inhibition of AT1a receptors in the paraventricular nucleus inhibits acute increases in mean arterial blood pressure in the rat. Am J Physiol Regul Integr Comp Physiol. 2010; 299(5):R1202-11
36). Zhu P, Chen JM, Chen SZ, Zhang C, Zheng SY, Long G, Chen J, Zhou ZL, Fan RX, Fan XP, Chen Y, Zhuang J. Matrine inhibits vascular smooth muscle cell proliferation by modulating the expression of cell cycle regulatory genes. Acta Pharmacol Sin 2010; 31:1329-35
37). Weihong Tu, Xin Xu, Lisheng Peng, Xiaofen Zhong, Wenfeng Zhang, Mangala M. Soundarapandian, Cherine Balel, Manqi Wang, Nali Jia, Wen Zhang, Frank Lew, Sic Lung Chan, Yanfang Chen, and Youming Lu. DAPK1 interaction with NMDA receptor NR2B subunits mediates brain damage in stroke. Cell 2010,140(2):222-34
38). Shuzhen Chen, Guangze Li, Wenfeng Zhang, Jinju Wang, Curt D. Sigmund, James E. Olson, Yanfang Chen*. Ischemia induced brain damage is enhanced in human renin and angiotensinogen double transgenic mice. Am J Physiol Regul Integr Comp Physiol 2009,297(5):R1526-31