Department of Pharmacology & Toxicology

Norma C. Adragna, Ph.D., Interim Chair

Chen

 

Yanfang Chen, Ph.D., M.D., FAHA

Associate Professor
Department of Pharmacology & Toxicology
Department of Medicine (Adjunct Faculty)
Department of Neurology (Residency Program Core Faculty)

 

Campus Address : 210 Health Sciences
Office: (937) 775-3265
Lab: (937) 775-4160
Fax: (937) 775-7221
E-mail: yanfang.chen@wright.edu


Education

M.D. (1987) Nanhua University Medical College
Ph.D. (1995) Beijing University Medical Center
Postdoctoral (1999-2002) Wright State University Boonshoft School of Medicine

Research Interests

Integrative and Translational Cardiovascular and Cerebrovascular Research: ischemic stroke and hypertension; stem cell therapy (angiogenesis and neurogenesis); diabetic complications; cellular microvesicles (MVs) and exosomes.

Approaches: Contemporary techniques are used for my studiesat molecular, cellular and in vivo levels, such as telemetric cardiovascular monitoring, brain microinjection, in situ hybridization, real-time RT-PCR, gene transfection, RNA interference (RNAi), nanoparticle tracking analysis (NTA). The cutting-edge methodologies such as mass spectral (ms), mRNA/microRNA deep sequencing (RNAseq), yeast-two-hybrid (Y2H) are applied through collaboration with the experts in these areas. 

Summary of My Research Emphasis

  1. Study of the role of renin-angiotensin system (RAS) in vascular disease including hypertension and stroke. 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.
  2. Study of stem cell-based and gene-based avenues for treating 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.
  3. Study of the role of extracellular MVs and Exosomes in modulating EPC-EC-SMC communication.Accumulating evidence indicate that extracellular MVs and exosomescould be the biomarkers and therapeutic targets for various diseases. The long-term objective in my laboratory is to understand the roles and mechanisms of extracellular MVs and exosomes mediated EPC-EC-SMC communication in modulating vascular function, and their implications in diseases.

Peer-Reviewed Publications

  1. Chen Y, Morris M. Differentiation of brain angiotensin type 1a and 1b receptor mRNAs: a specific effect of dehydration. Hypertension 2001; 37:692-699.
  2. Zhou Y, Chen Y, Dirksen WP, et al. AT1b receptor predominantly mediates contractions in major mouse blood vessels. Circ Res. 2003; 93:1089-1094.
  3. Chen Y, Rocha MJ, Morris M. Osmolality regulation of angiotensin AT1 receptor subtypes in mouse brain. Brain Res 2003; 965:35-44.
  4. Chen H, Morris M and Chen Y. Rapid neurosecretory and cardiovascular response to osmotic stimulation in conscious mice. Neuroendocrinology 2004; 80: 225-232.
  5. Adragna NC, Chen Y, Delpire E, et al. Hypertension in K-Cl cotransporter-3 knockout mice. Adv Exp Med Biol2004; 559:379-85.
  6. Chen Y, Liu-Stratton Y, Hassanain H, Cool DR and Morris M. Dietary sodium regulates angiotensin AT1a and AT1b mRNA expression in mouse brain: analyzed by quantitative real-time PCR. Exp Neurol. 2004; 188:238-245.
  7. Rocha MJA, Chen Y, Oliveira GR, et al. Physiological regulation of brain angiotensin receptor mRNA in AT1a deficient mice. Exp Neurol. 2005; 195: 229-35.
  8. Chen Y, Chen H and Morris M. Enhanced osmotic responsiveness in angiotensin AT1a receptor deficient mice: evidence for a role of AT1b receptors. Exp Physiol. 2005: 90:739-746.
  9. Zhou Y, Dirksen WP, Chen Y, et al. A major role for AT1b receptor in mouse mesenteric resistance vessels and its distribution in heart and neuroendocrine tissues. J Mol Cell Cardiol. 2005;38:693-696.
  10. Chen Y, Joaquim LF, Farah V, et al. Cardiovascular autonomic control in mice lacking angiotensin AT1a receptors. Am J Physiol Regul Integr Comp Physiol 2005; 288: R1071-R1077.
  11. Chen Y, Chen H, Chappell M, et al. Adenovirus mediated small interference RNA for silencing angiotensin AT1a receptors in mouse brain. Hypertension 2006; 47:230-237.
  12. Chen Y, Oroszi TL, Morris M. Salt consumption increases blood pressure and abolishes the light/dark rhythm in angiotensin AT1a receptor deficient mice. Physiol Behav. 2006; 88: 95-100.
  13. Farah V, Elased KM, Chen Y, et al. Nocturnal hypertension in mice consuming a high fructose diet. Auton Neurosci. 2006:130:41-50.
  14. Wichi RB, Farah V, Chen Y, et al. Deficiency in angiotensin AT1a receptors prevents diabetes-induced hypertension. Am J Physiol Regul Integr Comp Physiol.2007; 292: R1184–R1189.
  15. Zhong JH, Chen XP, Yun ML, Li WJ, Chen Y, Yao Z.Low-dose carvedilol reduces transmural heterogeneity of ventricular repolarization in congestive heart failure. Acta Pharmacol Sin. 2007; 28:1161-1165.
  16. Zhong JH, Chen XP, Zeng CF, Yun ML, Yang XW, Chen Y, Yao Z. Effect of benazepril on heart rate turbulence in patients with dilated cardiomyopathy. Clin Exp Pharmacol Physiol 2007; 34:612-616.
  17. Lin Z, Chen Y, Zhang W, et al. RNA interference shows interactions between brainstem angiotensin AT1 receptors and ACE2.Exp Physiol. 2008; 93:676-84.
  18. Zheng X, Chen S, Wang J, Yang T, Chen Y. Dilated cardiomyopathy with hypertension: prevalence and response to high dose of beta1-adrenergic receptor blocker therapy. Clin Exp Pharmacol Physiol 2009; 36:945-949.
  19. Chen S, Li G, Zhang W, Wang J, Sigmund CD, Olson JE, Chen Y. Ischemia induced brain damage is enhanced in human renin and angiotensinogen double transgenic mice. Am J Physiol Regul Integr Comp Physiol 2009, 297:R1526-31.
  20. Tu W, Xu X, Peng L, Zhong X, Zhang W, Soundarapandian MM, Balel C, Wang M, Jia N, Zhang W, Lew F, Chan SL, Chen Y, Lu Y. DAPK1 interaction with NMDA receptor NR2B subunits mediates brain damage in stroke. Cell 2010, 141, 28-46.
  21. Northcott CA, Watts S, Chen Y, et al. 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:R1202-11.
  22. 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.
  23. 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 Metab2011; 301:E62-E71.
  24. 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.
  25. 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.
  26. 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.
  27. 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.
  28. 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
  29. 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.
  30. 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 ONE2012;7(11): e50105.
  31. Zhao YH, Yuan B, Chen J, Feng DH, Zhao B, Qin C, Chen YFstrong>. Endothelial progenitor cells: therapeutic perspective for ischemic stroke. CNS Neurosci Ther.2013;19(2): 67–75
  32. 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
  33. 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
  34. 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
  35. 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
  36. 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
  37. 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
  38. 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.
  39. 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
  40. 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. AJP-Heart and Circulatory PhysiologyAm J Physiol Heart Circ Physiol. 2014 May 16. pii: ajpheart.00518.2013. [Epub ahead of print]
  41. Xiang Xiao, Yingxia Liu, Ran Fan, Xiaotang Ma, Jinju Wang, Bin Zhao, Yanfang Chen, Ji Chen. Cellular membrane microparticles: potential targets of combinational therapy for vascular disease. Current Vascular Pharmacology 2014 (in press)
  42. 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*. Effect of mesenchymal stem cell-derived microvesicles on treating pulmonary arterial hypertension. Acta Pharmacologica Sinica 2014 (in press)