Yongmei Chen, MD, PhD. 515 John Muir Drive, APT A424 Department of Anesthesia San Francisco, CA UCSF, 1001 Potrero Ave, 3C-38

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1 Yongmei Chen, MD, PhD 515 John Muir Drive, APT A424 Department of Anesthesia San Francisco, CA UCSF, 1001 Potrero Ave, 3C-38 Cell phone Education PhD, Neuroscience, University of Missouri-Columbia, Missouri, May 1998 MD, Medicine, Hunan Medical University, China, July 1990 Research Experience Assistant Researcher, Center for Cerebrovascular Research, University of California San Francisco, 7/2003- present Demonstrated that IGF-1 overexpression via gene transfer induces cerebral angiogenesis, neurogenesis, and improves stroke outcome in mice Studied mechanisms underlying neurovascular regeneration in ischemic stroke mice Demonstrated that angiogenic proteins HoxD3, Del-1, Netrin-1 promote cerebral angiogenesis in normal mice brain Found that ischemic stroke enhances the expression of proteases EMMPRIN and MMP-9 in mice brain Investigated mechanisms underlying physiological and pathological angiogenesis using animal models and human brain tissues Demonstrated elevated levels of pro-inflammatory cytokines such as IL-6, IL-1β in brain vascular malformations Post-Doctoral Fellow, Dr. Raymond Swanson s lab, Dept. of Neurology, University of California San Francisco, 9/1998-6/2003 Studied signaling pathways of neuronal death using primary cortical neuronal culture Demonstrated that astrocytes protect cortical neurons against various injuries by secreting antioxidants using primary co-culture systems Examined the function of glutamate transporters using specific knockout mice Demonstrated that antioxidant enzyme SOD protects neural cells against excitotoxic and oxidative injuries PhD student, Dr. Albert Sun s lab, Dept. of Pharmacology, University of Missouri, 7/1992-7/1998 Studied the role of free radicals in neuronal injury using PC12 cell culture Demonstrated chronic ethanol administration enhanced lipid peroxidation and cell death Examined the role of transcription factor NF-kB in neuronal inflammation and death Research Associate, Dr. 韩启德 s lab, 3 rd affiliated Hospital, Beijing Medical University, 9/1990 6/1992 Studied the role of α1-adrenoceptors in the pathophysiology of hypertension 1

2 Demonstrated altered expression of α1-adrenoceptor subtypes in blood vessels of spontaneously hypertensive rats Honors and Awards Young Investigator Travel Award from International Society of Neurochemistry and American Society of Neurochemistry (ASN/ISN meeting in Buenos Aires, Argentina), 2001 Superior Graduate Achievement Award from the Graduate School of University of Missouri-Columbia, Missouri, 1998 Young Investigator Travel Award from International Society of Neurochemistry and American Society of Neurochemistry (ASN/ISN meeting in Boston, USA) 1997 Young Investigator Award from Chinese Society of Cardiovascular Pharmacology (Shenyang, China), 1991 Research Funding R03 NS (PI: Yongmei Chen) NIH/NINDS $154,500 09/15/ /31/2011 Endothelial progenitor cells in brain vascular dysfunction Beginning Grant-in-Aid (PI: Yongmei Chen) American Heart Association $150,000 07/01/ /30/2010 Netrin-1 in Neurovascular Regeneration R21 NS (PI: Yongmei Chen) NIH/NINDS $360,000 05/01/ /31/2008 Del-1 induces therapeutic cerebral angiogenesis, F32 NS11044 (PI: Yongmei Chen) NIH/NINDS, $118,800 02/01/ /31/2003 The physiological function of neuronal glutamate transporter EAAT3 R01 NS (PI: William L Young) NIH/NINDS $1,893,750 06/01/ /31/2010 Hemodynamics of Cerebral Arteriovenous Malformations Role: Co-Investigator R01 NS (PI: Tomoki Hashimoto) NIH/NINDS $1,893,750 06/01/ /31/2011 Intracranial aneurysm pathogenesis: roles of vascular remodeling and inflammation Role: Co-Investigator 2

3 First authored-publications: Publications 1. Chen Y, Hao Q, Kim H, Su H, Letarte M, Karumanchi SA, Lawton MT, Barbaro NM, Yang GY, Young WL: Soluble endoglin modulates aberrant cerebral vascular remodeling. Annals of Neurology, 66:19-27, Chen Y, Zhu W, Bollen AW, Lawton MT, Barbaro NM, Dowd CF, Hashimoto T, Yang GY, Young WL: Evidence for inflammatory cell involvement in brain arteriovenous malformations. Neurosurgery, 62: , Chen Y, Fan Y, Poon KY, Achrol AS, Lawton MT, Zhu Y, McCulloch CE, Hashimoto T, Lee C, Barbaro NM, Bollen AW, Yang GY, and Young WL: MMP-9 expression is associated with leukocytic but not endothelial markers in brain arteriovenous malformations. Frontiers in Bioscience, 11: , Chen Y, Pawlikowska L, Yao JS, Shen F, Zhai W, Achrol AS, Lawton MT, Kwok PY, Yang GY, Young WL: Interleukin-6 involvement in brain arteriovenous malformations. Annals of Neurology, 59:72-80, Chen Y, Xu B, Arderiu G, Hashimoto T, Young WL, Boudreau N, Yang GY: Retroviral delivery of homeobox D3 gene induces cerebral angiogenesis in mice. J Cereb Blood Flow Metab, 24:1280-7, Chen Y, Swanson RA: The glutamate transporters EAAT2 and EAAT3 mediate cysteine uptake in cortical neuron cultures. J Neurochem, 84: , Chen Y, Swanson RA: Astrocytes and brain injury. J Cereb Blood Flow Metab (Review), 23: , Chen Y, Vartiainen NE, Ying W, Chan PH., Koistinaho J, Swanson RA: Astrocytes protect neurons from nitric oxide toxicity by a glutathione-dependent mechanism. J Neurochem, 77: , Chen Y, Chan PH, Swanson RA: Astrocytes overexpressing Cu,Zn superoxide dismutase have increased resistance to oxidative injury. Glia, 33:343-34, Chen Y, Ying W, Simma V, Copin J-C, Chan PH, Swanson RA: Overexpression of Cu,Zn superoxide dismutase attenuates oxidative inhibition of astrocyte glutamate uptake. J Neurochem, 75: , Chen Y, Sun AY: Activation of AP-1 transcription factor after extracellular ATP treatment in PC12 cells. Neurochem Res, 23: , Chen Y, Wixom P, and Sun AY: Enhanced (Na+K)-ATPase activity and expression in mouse brain after chronic ethanol administration. Neurochem Res, 22: , 陈咏梅 韩启德 : 大鼠肺动脉 肾上腺素受体及其亚型的分析. 中国药理学报,1992, 13: 陈咏梅 王宪 韩启德. 激活 ATP 依赖性钾通道是 CGRP 舒血管作用的机制之一. 北京医科大学学报 1991,23: Corresponding authored-publications: 3

4 1. Zhu W, Fan Y, Hao Q, Shen F, Hashimoto T, Yang GY, Gasmi M, Bartus RT, Young WL, Chen Y: Post-ischemic IGF-1 gene transfer promotes neurovascular regeneration after experimental stroke. J Cereb Blood Flow Metab, 29: , Zhu W, Fan Y, Frenzel T, Gasmi M, Bartus RT, Young WL, Yang GY, Chen Y: IGF-1 gene transfer enhances neurovascular remodeling and improves long-term stroke outcome in mice. Stroke, 39: , Zhu W, Khachi S, Hao Q, Young WL, Yang GY, Chen Y: Upregulation of EMMPRIN after permanent focal cerebral ischemia. Neurochem Int, 52: , Fan Y, Zhu W, Yang M, Zhu Y, Shen F, Hao Q, Young WL, Yang GY, Chen Y: Del-1 gene transfer induces cerebral angiogenesis in mice. Brain Res, 1219:1-7, 2008 Co-authored publications: 1. ZhuGe Q, Zhou M, Zheng W, Yang GY, Mao X, Xie L, Gourong C, Chen Y, Lawton MT, Young WL, Greenberg DA, Jin K: Notch1 signaling is activated in brain arteriovenous malformation in humans. Brain, 2009 (in press) 2. Weinsheimer S, Kim H, Pawlikowska L, Chen Y, Lawton MT, Sidney S, Kwok PY, McCulloch CE, Young WL: Ephrin receptor B4 (EPHB4) gene polymorphisms and risk of intracranial hemorrhage in patients with brain arteriovenous malformations. Circ Cardiovasc Genet, 2009 (in press) 3. Kim H, Marchuk DA, Chen Y, Su H, Yang GY, Young WL: Genetic considerations relevant to intracranial hemorrhage and brain arteriovenous malformations. Acta Neurochir Suppl, 105: , Fan Y, Shen F, Hao Q, Chen Y, Liu W, Su H, Young WL, Yang GY: Overexpression of Netrin-1 induces neovascularization in the adult mouse brain. J Cereb Blood Flow Metab, 28: , Shen F, Fan Y, SU H, Zhu Y, Chen Y, Liu W, Young WL, Yang GY: Adeno-associated viral vectormediated hypoxia-regulated VEGF factor gene transfer promotes angiogenesis following focal cerebral ischemia in mice. Gene Therapy, 15:30-39, Fan Y, Ye J, Shen F, Zhu W, Zhu Y, Yeghiazarians Y, Chen Y, Lawton MT, Young WL, Yang GY: Interleukin-6 stimulates circulating blood-derived endothelial progenitor cell angiogenesis in vitro. J Cereb Blood Flow Metab, 28:90-98, Hao Q, Chen Y, Zhu Y, Fan Y, Young WL, Yang GY: Neutrophil depletion decreases VEGFinduced focal angiogenesis in the mature mouse brain. J Cereb Blood Flow Metab, 27: , Shen F, Su H, Fan Y, Chen Y, Zhu Y, Liu W, Young WL, Yang G-Y: Adeno-associated viral vectormediated hypoxia-inducible vascular endothelial growth factor gene expression attenuates ischemic brain injury following focal cerebral ischemia in mice. Stroke 37:2601-6, Aoyama K, Suh SW, Hamby AM, Liu J, Chan WY, Chen Y, Swanson RA: Neuronal glutathione deficiency and age-dependent neurodegeneration in the EAAC1 deficient mouse. Nat Neurosci, 9:119-26, Suh SW, Garnier P, Aoyama K, Chen Y, Swanson RA: Zinc release contributes to hypoglycemiainduced neuronal death. Neurobiol Dis, 16:538-45, Duan S, Anderson CM, Keung EC, Chen Y, and Swanson RA: P2X7 receptor-mediated release of excitatory amino acids from astrocytes. J Neurosci. 23:

5 12. Suh SW, Aoyama K, Chen Y, Garnier P, Matsumori Y, Gum E, Liu J, Swanson RA: Hypoglycemic neuronal death and cognitive impairment are prevented by poly(adp-ribose) polymerase inhibitors administered after hypoglycemia. J Neurosci, 23: , Ying W, Chen Y, Alano C, Swanson RA: Tricarboxylic acid cycle substrates prevent PARPmediated death of neurons and astrocytes. J Cereb Blood Flow Metab. 22: , Ying W, Sevigny M, Chen Y, Swanson RA: Poly(ADP-ribose) glycohydrolase mediates excitotoxic and oxidative neuronal death. Proc Natl Acad Sci U S A, 98: , Ying W, Anderson CM, Chen Y, Stein BA, Fahlman CS, Copin J-C, Chan PH, Swanson RA: Differing effects of copper, zinc dismutase overexpression on neurotoxicity elicited by nitric oxide, reactive oxygen species, and excitotoxins. J Cereb Blood Flow Metab. 20: , Draczynska-Lusiak B, Chen Y, Sun AY: Oxidized LDL activates NF-kB binding activity and induce apoptosis in PC12 cells. NeuroReport, 9: , Sun AY, Chen Y: Oxidative stress and neurodegenerative disorders. J Biomed Sci (Review) 5: , Sun AY, Chen Y, Cheng Y, and Wixom P: Ethanol enhanced lipid peroxidation and cell death in PC12 cells. Neurochem Res. 22: , 韩启德 陈咏梅 : 自发性高血压大鼠主动脉磷酸肌醇生成异常. 基础医学与临床, 1992, 12: 韩启德 陈咏梅 : 缺氧对 1 受体不同亚型血管收缩效应影响的差别. 生理学报, 1993,45: 韩启德 陈咏梅 : 大鼠主动脉 α 1 肾上腺素受体收缩效应的两成分分析. 北京医科大学学报,1992,24: 韩启德 李金玲 陈咏梅 : 自发性高血压大鼠血管 α 1 肾上腺素受体亚型的改变. 生理学报,1992,44: 韩启德 李金玲 陈咏梅 王宪 赵一鸣 : 内毒素血症大鼠血管 α 1 肾上腺素受体及其亚型的改变. 北京医科大学学报, 1992, 24: