Xin Wang Lab: Neuroapoptosis Drug Discovery

My group focuses on the identification of candidate therapeutics and potential targets for therapeutic intervention in neurodegenerative disorders including Huntington’s Disease, Stroke, Amyotrophic Lateral Sclerosis and Alzheimer’s Disease. Another main interest concerns the molecular and cellular apoptotic mechanism of neurodegenerative diseases, because a greater understanding will help in the development of new therapies that act on disease genes. We also work on chemistry and structure-activity relationship and stem cell therapy.

Profile of Xin Wang, MD, PhD

Training

  • 1986 B.S. Liaoning Normal University, Dalian, China
  • 1989 M.S. University of Science & Technology of China, Hefei, China
  • 1999 Ph.D. The Hebrew University of Jerusalem, Israel
  • 1999-2001 Postdoctoral Fellow, Medical School, University of Michigan, Ann Arbor
  • 2001-2003 Postdoctoral Fellow, Department of Neurosurgery, Brigham and Women's Hospital/Harvard Medical School, Boston

Academic Appointments

  • 2003-2007 Instructor of Neurosurgery, Brigham and Women's Hospital/Harvard Medical School, Boston
  • 2005- Visiting Professor, Weifang Medical College, Weifang, China
  • 2005- Visiting Professor, Qingdao University, Qingdao, China
  • 2007- Assistant Professor of Neurosurgery, Brigham and Women’s Hospital/Harvard Medical School, Boston

Editorial Reviewer

  • Pharmacological Research
  • Neurobiology of Disease
  • European Journal of Neuroscience

Professional Memberships

  • The Federation of American Societies for Experimental Biology
  • Society for Neuroscience
  • The Cell Death Society
  • American Chemical Society

Lab Members

Principal Investigator:

Xin Wang, MD, PhD
Neuroscientist, Brigham and Women's Hospital
Assistant Professor of Surgery, Harvard Medical School
xwang2@partners.org
Fax: 617-732-6767

Research Technicians

  • Ana C. Sirianni
  • Rachna S. Pandya
  • Anastasios Fotinos

Postdoc Research Fellows

  • Jiying Jiang
  • David Li
  • Bharati Sinha
  • Yongjin Zhou
  • Ji Wang
  • Xinmu Zhang
  • Hannah Zhou

Publications

Zhou H, Wang J, Jiang J, Stavrovskaya IJ, Li MC, Li W, Wu Q, Zhang XM, Luo CL, Zhou S, Sirianni AC, Sarkar S, Kristal BS, Friedlander RM, and Wang X. N-acetyl-serotonin offers neuroprotection through inhibiting mitochondrial death pathways and autophagic activation in experimental models of ischemic injury. Journal of Neuroscience. 2014. 34(8): 2967–78

Wang J, Dong WW, Zhang WH, Zheng J, Wang X. Electrical Stimulation of Cerebellar Fastigial Nucleus: Mechanism of Neuroprotection and Prospects for Clinical Application against Cerebral Ischemia.CNS Neuroscience & Therapeutics. 2014. 20(8): 710-6

Wang X. The antiapoptotic effects of melatonin in neonatal hypoxic-ischemic brain injury. JSM Neurosurgery & Spine. 2014. 2(2): 1-3

Wang X, Guan YJ, Fu Y, Zhou S, Qin ZH. Melatonin’s antiapoptotic activity in neurodegenerative diseases In: Melatonin:  Therapeutic Value and Neuroprotection, V Srinivasan, Gabriella Gobbi, Samuel D Shillcutt, Sibel Suzen, ed., Taylor & Francis-CRC Press. 2014. p. 111-132

Wang XL, Zhao YS, and Wang X. Umbilical cord blood cells regulate the differentiation of endogenous neural stem cells in hypoxic ischemic neonatal rats via the hedgehog signaling pathway. Brain Research. 2014. 1560:18-26

Jiang JY, Yu SN, Jiang ZC, Liang CH, Yu WB, Li J, Du XD, Wang HL, Gao XH, and Wang X. N-acetyl-serotonin protects HepG2 cells from oxidative stress injury induced by hydrogen peroxide. Oxidative Medicine and Cellular Longevity. 2014. 2014: 1-15

Song X, Zhu J, Xu R, Xie F, Zhu HY, and Wang X. Hemin offers neuroprotection through inducing exogenous neuroglobin in focal cerebral hypoxic-ischemia in rats. International journal of Clinical and Experimental pathology. 2014. 7(5): 2163-71

Wang L, Yu L, Zhang TL, Wang LN, Leng ZT, Guan YJ, and  Wang X. HMGB1 enhances embryonic neural stem cell proliferation by activating the MAPK signaling pathway. Biotechnology letters. 2014. 36(8): 1631-9

Liu HC, Chen YC, Zhou FH, Jie LL, Pu LD, Ju J, Li FJ, Dai ZG, Wang X, Zhou SH. Sox9 regulates hyperexpression of Wnt1 and Fzd1 in human osteosarcoma tissues and cells. International journal of Clinical and Experimental Pathology. 2014. In press

Xie F, Xu R, Song X, Zhu HY, Wang X, Zhu J. The joint protective effect of exogenous neuroglobin and hemin in rat focal ischemic brain tissues. International journal of Clinical and Experimental Medicine. 2014. In press 11.

Pandya RS, Zhu H, Li W, Bowser R, Friedlander RM, and Wang X. Therapeutic neuroprotection for amyotrophic lateral sclerosis. Cellular and Molecular Life Sciences. 2013. 1-17

Yu S, Zheng J, Jiang Z, Shi C, Li J, Du X, Wang H, Jiang J, and Wang X. Protective effect of N-acetylserotonin against acute hepatic ischemia-reperfusion injury in mice. International Journal of Molecular Sciences, 2013. 14, 17127-60

Zhou F, Guan Y, Chen Y, Zhang C, Yu L, Gao H, Du H, Liu B, and Wang X. miRNA-9 expression is upregulated in the spinal cord of G93A-SOD1 transgenic mice. International journal of Clinical and Experimental pathology, 2013, 6(9), 1826-38

Zhang Y, Sirianni AC, Jinho Kim, Smith K, Cormier K, Jiang J, Ferrente R, Bowser R, Day, AL, Wang X, and Friedlander RM. Melatonin inhibits the caspase-1/cytochrome c/caspase-3 cell death pathway, inhibits MT1 receptor loss and delays disease progression in a mouse model of amyotrophic lateral sclerosis. Neurobiology of Disease. 2013. 55, 26-35

Yu L, Guan Y, Wu X, Chen Y, Liu Z, Du H, Wang X. Wnt Signaling is Altered by Spinal Cord Neuronal Dysfunction in Amyotrophic Lateral Sclerosis Transgenic Mice. Neurochem Res. 2013. 38(9), 1904-13

Fu W, Zheng Z, Zhuang W, Chen D, Wang XC, Sun X, and Wang X. Neural metabolite changes in corpus striatum after rat multipotent mesenchymal stem cells transplanted in hemiparkinsonian rats by magnetic resonance spectroscopy. International Journal of Neuroscience. 2013. 123(12): 883-91

Li X, Guan Y, Chen Y, Zhang C, Shi C, Zhou F, Yu L, Juan J, and Wang X. Expression of Wnt5a and its receptor Fzd2 is changed in the spinal cord of adult amyotrophic lateral sclerosis transgenic mice. International journal of Clinical and Experimental pathology, 2013. 6(7): 1245-60

Wang S, Guan Y, Chen Y, and Wang X. The role of Wnt1 and Fzd1 in the pathogenesis of spinal cord of ALS transgensis mice. Biotechnology Letters. 2013. 35(8): 1199-207

Du R, Zhou J, Lorenzano S, Charoenvimolphan N, Qian BG, Rost N, Wang J, Zhang XM, Wang X, Berndt A, Devan WJ, Valant VJ, Furie KL, Rosand J, Friedlander R, Paigen B, Weiss ST. ZBTB7C Is associated with severity of infarction in cerebral ischemia. Stroke. 2013. 44 (2)

Ma H, Sinha B, Pandya RS, Lin N, Popp AJ, Li J, Yao J, and Wang X. Therapeutic hypothermia as neuroprotective strategy in neonatal hypoxia-ischemic brain injury and traumatic brain injury. Current Molecular Medicine. 2012. 12:1282-96

Chen Y, Guan Y, Liu H, Wu X, Yu L, and Wang X. Activation of the Wnt/β-catenin signaling pathway promotes the proliferation and differentiation of neural stem cells in the adult spinal cord of ALS transgenic mice. Biochemical and Biophysical Research Communications. 2012. 420, 397-403

Lv L, Han X, Sun Y, Wang X, and Dong Q. Valproic acid improves locomotion in vivo after SCI and axonal growth of neurons in vitro. Experimental Neurology 2012. 233, 783-90

Pandya RS, Mao LL, Zhou EW, Bowser R, Zhu Z, Zhu Y, and Wang X. Neuroprotection for Amyotrophic Lateral sclerosis: role of stem cells, growth factors and gene therapy. Central Nervous System Agent In Medicinal Chemistry. 2012. 12, 15-27

Chen Y, Guan Y, Zhang Z, Liu H, Wang H, Yu L, Wu, X, and Wang X. Wnt signaling pathways are involved in pathogenesis of amyotrophic lateral sclerosis in adult transgenic mice. Neurological Research. 2012. 34: 390-9

Wang X, Sirianni AC, Pei Z, Cormier, K, Smith K, Jiang J, Zhou S, Zeng J, Mao L, Wang H, Zhao Z,Yano H, Kim JE, Li W, Bouhajib M, Ferrante RJ, and Friedlander RM. Melatonin delays progression of Huntington’s disease by inhibiting the mitochondrial death pathway and restoring the downregulation of melatonin receptor 1A. Journal of Neuroscience. 2011. 31, 14496-507

Wang X. Recent advances in stroke: approaches, treatments, and molecular mechanisms. Central Nervous System Agent In Medicinal Chemistry. 2011. 11 (2), 1

Sinha B, Yano, H, Li, W, Wang, X, Friedlander RM. Receptor inducing protein-2 (Rip2) deficiency is neuroprotective against hypoxia-ischemic brain injury in newborn mice. Pediatric Research. 2011. 70(5): 66

Pandya RS, Mao LL, Zhou H, Zhou S, Zeng J, Popp AJ and Wang X. Central nervous system agents for ischemic stroke: neuroprotection mechanisms. Central Nervous System Agent In Medicinal Chemistry. 2011. 11, 81-97

Zhang Y, Wang X, Baranov SV, Zhu S, Huang Z, Fellows-Mayle W, Jiang J, Day AL, Kristal BS, Friedlander RM. Dipyrone Inhibits neuronal cell death and diminishes hypoxic/ischemic brain injury. Neurosurgery. 2011. 69, 942-56

Lv E, Tang YP, Han X, Wang X, and Dong Q. Therapeutic application of histone deacetylase Inhibitors for stroke. Central Nervous System Agent In Medicinal Chemistry. 2011. 11, 138-149

Wang X, Pandya R, Yao J, Ma H, Li J. Targeting caspases in neonatal hypoxia-ischemic brain injury and traumatic brain injury. Neurodegeneration: Theory, Disorders and Treatments. NOVA Science Publishers, Inc. New York, 2011. p. 125-54

Wang X. The anti-apoptotic activities of melatonin in neurodegenerative diseases. CNS Neuroscience & Therapeutics. 2009. 15: 345-57

Wang X, Figueroa, BE, Stavrovskaya IG, Zhang Y, Sirianni AC, Zhu S, Day, AL, Kristal BS, and Friedlander RM. Methazolamide and melatonin inhibit mitochondrial cytochrome c release and are neuroprotective in experimental models of ischemic injury. Stroke. 2009. 40, 1877-85

Yu L, Guan Y, Gao Y, Wang X. RPL30 and HMGB1 are required for neurulation in golden hamster. The International Journal of Neuroscience. 2009. 119, 1076-90

Wang X, Zhu S, Pei Z, Drozda M, Stavrovskaya IG, Del Signore, SJ, Cormier K, Shimony E, Wang H, Kristal BS, Ferrante, R, and Friedlander RM. Inhibitors of cytochrome c release with therapeutic potential for Huntington’s disease. Journal of Neuroscience. 2008. 28, 9473-85

Zhang W, Wang H, Wang X, Narayanan M, Stavrovskaya IG, Kristal BS and Friedlander RM Nortriptyline, a tricyclic antidepressant, protects mitochondria and reduces cerebral ischemia/hypoxia Injury. Stroke. 2008. 39, 455-62

Wang H, Guan Y, Wang X, Smith K, Kerry C, Zhu S, Stavrovskaya IG, Huo C, Ferrante RJ, Kristal BS and Friedlander RM. Nortriptyline delays disease onset in models of Huntington’s disease and amyotrophic lateral sclerosis. European Journal of Neuroscience. 2007. 26, 633-41

Zhang X, Li R, Wang X and Zhou S. The effects of copper-phenanthroline pentachlorophenol-induced adaptation and cell death of escherichia coli.  Biomedical and Environmental Sciences. 2007.20 (2): 106-12

Guan Y, Wang X, Wang H, Kawagishi K, Ryu H, Huo C, Shimony E, Kristal BS, Kuhn HG and Friedlander RM. Increased cell proliferation and neurogenesis in the adult ALS transgenic mice. Journal of Neurochemistry. 2007. 102 (4): 1125-38

Frusic-Zlotkin M, Raichenberg D, Wang X, David M, Michel B and Milner Y. Apoptotic mechanism in pemphigus autoimmunoglobulins-induced acantholysis – possible involvement of the EGF receptor. Autoimmunity. 2006. 39: 563-75

Frusic-Zlotkin M, Raichenberg D, Wang X, David M, Michel B and Milner Y. Signaling elicited by pemphigus (PV)-IgG in cultured epidemal cells: involvement of EGF and MAPK casades. Journal of Investigative Dermatology, 2006. 126: 8

Wang X, Narayanan M, Bruey JM, Rigamonti D, Cattaneo E, Reed JC and Friedlander RM. Protective role of Cop in Rip2/Caspase-1/Caspase-4-mediated HeLa cell death. Biochimica et Biophysica Acta – Molecular Basis of Disease. 2006. 1762: 742-54

Wang X, Wang H, Figueroa BE, Zhang W, Huo C, Guan Y, Zhang Y, Bruey JM,  Reed JC and Friedlander RM. Dysregulation of Cop and Rip2 mediates aberrant caspase-1 activation in Huntington's Disease. Journal of Neuroscience. 2005. 25: 11645-54

Wang X, Bregegere F, Soroka Y, Frusic-Zlotkin M and Milner Y. Replicative senescence enhances Apoptosis induced by pemphigus autoimmune antibodies in human keratinocytes. FEBS Letters. 2004. 567: 281-6

Wang X, Bregegere F, Kayat A,  Redziniak G and Milner Y. Biomarkers of apoptosis are associated with cellularaging in human epidermis and keratinocyte cultures. Mechanisms of Ageing and Development. 2004. 125: 237-49

Wang X, Brégégère F, Frusic-Zlotkin M, Feinmesser M, Michel B and Milner Y. Possible apoptotic mechanism in epidermal acantholysis induced by pemphigus vulgaris Autoimmunoglobulins. Apoptosis. 2004. 9: 76-88

Frusic-Zlotkin M, Wang X, Brégégère F, Michel B and Milner Y. Pemphigus vulgaris IgG-induced acantholysis in organ and cell culture: Kinetics of appearance of apoptotic effectors. Journal of Investigative Dermatology. 2003. 121(1): 0100

Zhang W, Wang X, Narayanan M, Zhang Y, Huo C, Reed JC and Friedlander RM. Fundamental role of the Rip2/caspase-1 pathway in ischemia-mediated neuronal cell death. Proceedings of the National Academy of Sciences of the United States of America. 2003. 100: 16012-7

Wang X, Zhu S, Drozda M, Zhang W, Stavrovskaya I, Cattaneo, E, Ferrante, R, Kristal BS and Friedlander RM. Minocyline inhibits caspase-dependent and caspase- independent mitochondrial cell death pathways. Proceedings of the National Academy of Sciences of the United States of America 2003. 100: 10483-7

Wang X, Shao Z, Zetoune F, Zeidler M, Gowrishankar K and Vincenz C. NRADD, a novel membrane protein with a death domain involved in mediating apoptosis in response to ER Stress. Cell Death and Differentiation 2003. 10: 580-91

Frusic-Zlotkin M, Goldshmit D, Wang X, David M, Maron L, Michel B, Milner Y. Pathogenicity test of pemphigus vulgaris autoantibodies: Use of enzymatic activity of the apoptotic caspase 3. Journal of Investigative Dermatology. 2002. 119(1): Part 2, 325

Wang X, Bauer J, Li Y, Shao Z, Zetoune F, Cattaneo E and Vincenz C. Characterization of the p75NTR apoptotic signaling pathway using a novel neuroal cellular model. The Journal of Biological Chemistry. 2001. 276: 33812-20

Guo R, Huber-Lang M, Wang X, Sarma, V, Padgaonkar V, Craig, R, Riedemann N, S.  McClintock S, Hlaing T, Shi M and Ward PA. Anti apoptotic effect of anti-C5a in CLP-induced sepsis rats. The Journal of Clinical Investigation 2000. 106: 1271-80

Petropoulos I, Conconi M, Wang X, Hoenel B, Bregegere F, Milner Y and Friguet B.  Increase of modified protein is associated with decrease of proteasome content and activity in aging epidermal cells. J. Gerontology A-Biol.  2000. 55A, B220-7

Wang X, Bregegere F, Goldshmit D, and Milner Y. The autoimmune pemphigus vulgaris-IgG (PV-IgG), similar to anti Fas receptor IgG (Fas-IgG), induces changes in signaling effectors leading to apoptosis of epidermal cells. Journal of Autoimmunity. 1999. 12: 65

Wang X, Bregegere F, Frusic-Zlotkin M, Michel B and Milner Y. The similarity between auto-immune PV-IgG and anti-Fas receptor IgG (FAS-IgG) in induction of cultured keratinocytes apoptosis. Journal of Investigative Dermatology. 1999. 112(4): 602

Wang X, Bregegere F, Frusic-Zlotkin M, Michel B, Milner Y. The similarity between PV-IgG and anti-FAS receptor IgG (FAS-IgG) in induction of cultured keratinocytes apoptosis. Journal of Investigative Dermatology. 1999. 112(4): 623

Milner Y, Merau P, Kiefer H, Feinmesser M, Bregegere F, Zlotkin M, Wang X, Michel B. Pemphigus, an autoimmune disease of the skin: cell-cell separation versus membranal signaling and apoptosis in acantholysis. In: The Decade of Autoimmunity, Y. Schoenfeld, ed., Elsevier Science 1999. p. 197-207

Wang X, Redziniak G, Bregegere , and Milner Y. Aged keratinocytes display increased levels of apoptosis-associated proteins, and increased susceptibility to apoptosis induction. Journal of Dermatological Science.1998. 16, 555, S84

Frankenburg S. Wang X and Milner Y. Vitamin A inhibits cytokines produced by type 1 lmphocytes in vitro via protein kinase C pathway. Cellular Immunology 1998. 185: 75-81

Wang X, Bregegere, F, Feinmesser M, Michel B, & Milner Y. Pemphigus-IgG (PV IgG) induces apoptosis in lesional skin and in cell and organ cultures. Journal of Dermatological Science. 1998. 16, no.1001:513, S41

Zhou S and Wang X. The correlation of bond-parameter and topological index of lattice enthalpy. Chemical Research and Application 1992. 4: 48-52.

Wang X, Zhou S, Qian Y and Chen Z. The research of phase and conductivity of Ba-La-Cu-O, Ba2xSrxLaCu3O7-d, Ba2La1xCexCu3O7-delta systems. Bulletin of the Chinese Ceramic Society.1991. 10:12-7

Wang X (author, Biological Chemistry Section) Modern All subjects dictionary, (Xioushong Li Ed.), Anhui People Publishing House, Hefei, 1990.

Wang X (author, Biological Chemistry Section) The Chinese encyclopedia dictionary (GuangYuan Yu, Ed.) Huaxia Publishing House, Beijing, 1990.

Zhou S, Wang X and Nie S. The electrode potentials and atomic sotentiols scale of the hardness- softness of acids and bases. Chemical Research and Application 1990. 2: 88-93

Wang X, Qian Y, Chen Z, Wen Y and Zhang, Q The synthesis, conductivity of Li-Ti- Cu-O system composite oxide compound. Guisuanyan Tongbao 1989. 8: 11-5

Gao C, Wang X, Cheng T, Liu Y, Liu W, Qian Y and Chen Z. Structure study of Ba2CeCu3O7.4, Solid StateCommunication (United Kingdom). 1989. 70: 631-5

Wang X, Qian Y, Chen Z, Cheng T, Wen Y and Zhang Q. The crystal structure, conductivity and phase of Ba2CeCu3O7-detla composite oxide compound. Rare Earth 1989. 1: 1-5

Qian Y, Wang X, Chen Z, Wen Y, sheng J, Fang M, Sun S, and Zhang Q. Phase situation of superconductivity of Ba-Y-Cu-O doped with K+ and Li+. Bulletin of Chinese Sillicate Society