Zhigang Xie, Ph.D.
Assistant Professor of Pharmacology and Neurosurgery
Ph.D.: University of Alabama, Birmingham
Neural stem cells are self-renewing precursor cells that can generate multiple types of differentiated cells of the nervous system. Dr. Xie’s research focuses on the mechanisms regulating neural stem cell self-renewal and differentiation. Understanding these mechanisms may lead to improved treatments for several human diseases. First, neural stem cells or their derivatives may be used in cell replacement therapies for treating neurodegeneration and neuronal injury. These therapies will require precise control of the fate of transplanted neural stem cells or their derivatives. Second, abnormal neural stem cell self-renewal and differentiation have been implicated in developmental disorders such as autism and mental retardation. Targeting molecular pathways regulating neural stem cell self-renewal and differentiation may ameliorate the neural stem cell defects in patients suffering from these disorders. Third, deficient adult neurogenesis in the brain has been linked to several mental illnesses such as depression. The knowledge on neural stem cell self-renewal and differentiation may lead to the identification of novel drug targets for treating these mental illnesses. Last, increased self-renewal of neural stem cells may contribute to the development of malignant brain cancer. Chemicals that inhibit neural stem cell self-renewal or promote neural stem cell differentiation may serve as a novel class of drugs for treating malignant brain cancer.
Dr. Xie uses the embryonic mouse brain to study how gene knockout or knockdown affects neural stem cell self-renewal and differentiation in vivo. Gene knockdown is achieved by an in utero electroporation technique, which allows the delivery of plasmids for silencing endogenous proteins or overexpressing exogenous proteins into neural stem cells of the embryonic mouse brain. Current projects include investigating the role of metabolic pathways and autism-associated genes in neural stem cell self-renewal and differentiation. In addition, Dr. Xie is collaborating with other faculty members to determine the role of these pathways in the self-renewal of stem-like cells in brain tumors.
Pinheiro EM, Xie Z, Norovich AL, Vidaki M, Tsai LH, Gertler FB. Lpd depletion reveals that SRF specifies radial versus tangential migration of pyramidal neurons. Nat Cell Biol. 2011 Jul 24;13(8):989-95. doi: 10.1038/ncb2292.PMID:21785421. PMC 3149714. Full Article: .
Saffary R, Xie Z. FMRP regulates the transition from radial glial cells to intermediate progenitor cells during neocortical development. J Neurosci. 2011 Jan 26;31(4):1427-39. PMID:21273427. Full Article: .
Mahjoub MR, Xie Z, Stearns T. Cep120 is asymmetrically localized to the daughter centriole and is essential for centriole assembly. J Cell Biol. 2010 Oct 18;191(2):331-46. PMID:20956381. PMC2958470. Full Article: .
Frank CL, Ge X, Xie Z, Zhou Y, Tsai LH. Control of activating transcription factor 4 (ATF4) persistence by multisite phosphorylation impacts cell cycle progression and neurogenesis. J Biol Chem. 2010 Oct 22;285(43):33324-37. Epub 2010 Aug 19. PMID:20724472. PMC2963346. Full Article: .
Buchman JJ, Tseng HC, Zhou Y, Frank CL, Xie Z, Tsai LH. Cdk5rap2 interacts with pericentrin to maintain the neural progenitor pool in the developing neocortex. Neuron. 2010 May 13;66(3):386-402. PMID:20471352. Abstract: .
Davis DA, Wilson MH, Giraud J, Xie Z, Tseng HC, England C, Herscovitz H, Tsai LH, Delalle I. Capzb2 interacts with beta-tubulin to regulate growth cone morphology and neurite outgrowth. PLoS Biol. 2009 Oct;7(10):e1000208. Epub 2009 Oct 6. PMID:19806181. PMC: 2748697. Full Article: .
Xie Z, Moy LY, Sanada K, Zhou Y, Buchman JJ, Tsai LH. Cep120 and TACCs control interkinetic nuclear migration and the neural progenitor pool. Neuron. 2007 Oct 4;56(1):79-93. PMID:17920017. PMC: 2642594. Full Article: .
Xie Z, Sanada K, Samuels BA, Shih H, Tsai LH. Serine 732 phosphorylation of FAK by Cdk5 is important for microtubule organization, nuclear movement, and neuronal migration. Cell. 2003 Aug 22;114(4):469-82. PMID:12941275. Abstract: .
Xie Z, Fang M, Bankaitis VA. Evidence for an intrinsic toxicity of phosphatidylcholine to Sec14p-dependent protein transport from the yeast Golgi complex. Mol Biol Cell. 2001 Apr;12(4):1117-29. PMID:11294911. PMC32291. Full Article: .
Xie Z, Fang M, Rivas MP, Faulkner AJ, Sternweis PC, Engebrecht JA, Bankaitis VA. Phospholipase D activity is required for suppression of yeast phosphatidylinositol transfer protein defects. Proc Natl Acad Sci U S A. 1998 Oct 13;95(21):12346-51. PMID:9770489. PMC 22834. Full Article: .