X. William Yang, M.D., Ph.D.

Professor, Psychiatry and Biobehavioral Sciences

Biography

Dr. X. William Yang is a professor in the Department of Psychiatry & Biobehavioral Sciences at David Geffen School of Medicine at UCLA. He is also a member of the Center for Neurobehavioral Genetics at Semel Institute for Neuroscience & Human Behaviors, and a member of the Brain Research Institute at UCLA. He has served as a regular member at the NIH's Cell Death in Neurodegeneration (CDIN) Study Section, a Scientific Advisory Board member of the Hereditary Disease Foundation, and a faculty member for Faculty 1000 Medicine?s Neurogenetics Section. William grew up in Tianjin, China. He obtained a combined M.S. and B.S. degrees with summa cum laude from Molecular Biophysics & Biochemistry Department at Yale University in 1991. He received Ph.D. in Molecular Genetics and Neuroscience from Rockefeller University in 1998. During his PhD thesis research with Dr. Nathaniel Heintz, William co-invented (together with Nat Heintz and Peter Model) the first recombineering technology to modify large pieces of DNA called Bacterial Artificial Chromosomes (BACs) and to generate BAC transgenic mice. The BAC transgenic technology is now a widely-used tool to generate transgenic animals for analyses of gene expression and gene function, and for modeling human diseases. After obtaining his Ph.D. degree, William went on to complete his M.D. training from Weill Medical College of Cornell University in 2000, and his Medicine Internship at New York-Presbyterian Hospital in 2001. After a brief postdoctoral training with Nat Heintz at Rockefeller University, William joined UCLA as an Assistant Professor in Dept. of Psychiatry in 2002.

Haustein MD, Kracun S, Lu XH, Shih T, Jackson-Weaver O, Tong X, Xu J, Yang XW, O'Dell TJ, Marvin JS, Ellisman MH, Bushong EA, Looger LL, Khakh BS.   Conditions and constraints for astrocyte calcium signaling in the hippocampal mossy fiber pathway, Neuron, 2014; 82(2): 413-29..

Cui Yijun, Ostlund Sean B, James Alex S, Park Chang Sin, Ge Weihong, Roberts Kristofer W, Mittal Nitish, Murphy Niall P, Cepeda Carlos, Kieffer Brigitte L, Levine Michael S, Jentsch James David, Walwyn Wendy M, Sun Yi E, Evans Christopher J, Maidment Nigel T, Yang X William   Targeted expression of μ-opioid receptors in a subset of striatal direct-pathway neurons restores opiate reward Nature neuroscience, 2014; 17(2): 254-61.

Lee C Y Daniel, Cantle Jeffrey P, Yang X William   Genetic manipulations of mutant huntingtin in mice: new insights into Huntington's disease pathogenesis The FEBS journal, 2013; 280(18): 4382-94.

Daggett Anthony, Yang X William   Huntington's disease: easing the NMDAR traffic jam Nature medicine, 2013; 19(8): 971-3.

Yue Zhenyu, Yang X William   Dangerous duet: LRRK2 and α-synuclein jam at CMA Nature neuroscience, 2013; 16(4): 375-7.

Southwell Amber L, Warby Simon C, Carroll Jeffrey B, Doty Crystal N, Skotte Niels H, Zhang Weining, Villanueva Erika B, Kovalik Vlad, Xie Yuanyun, Pouladi Mahmoud A, Collins Jennifer A, Yang X William, Franciosi Sonia, Hayden Michael R   A fully humanized transgenic mouse model of Huntington disease Human molecular genetics, 2013; 22(1): 18-34.

Yu-Taeger Libo, Petrasch-Parwez Elisabeth, Osmand Alexander P, Redensek Adriana, Metzger Silke, Clemens Laura E, Park Larry, Howland David, Calaminus Carsten, Gu Xiaofeng, Pichler Bernd, Yang X William, Riess Olaf, Nguyen Huu Phuc   A novel BACHD transgenic rat exhibits characteristic neuropathological features of Huntington disease The Journal of neuroscience : the official journal of the Society for Neuroscience, 2012; 32(44): 15426-38.

Shirasaki Dyna I., Greiner Erin R., Al-Ramahi Ismael, Gray Michelle, Boontheung Piamanee, Geschwind Daniel H, Botas Juan, Coppola Giovanni, Horvath Steve, Loo Joseph A, Yang X William.   Network organization of the huntingtin proteomic interactome in Mammalian brain Neuron, 2012; 75(1): 41-57.

Lu Xiao-Hong, Yang X William   "Huntingtin Holiday": Progress toward an Antisense Therapy for Huntington's Disease Neuron, 2012; 74(6): 964-6.

Gafni Juliette, Papanikolaou Theodora, Degiacomo Francesco, Holcomb Jennifer, Chen Sylvia, Menalled Liliana, Kudwa Andrea, Fitzpatrick Jon, Miller Sam, Ramboz Sylvie, Tuunanen Pasi I, Lehtimäki Kimmo K, Yang X William, Park Larry, Kwak Seung, Howland David, Park Hyunsun, Ellerby Lisa M   Caspase-6 Activity in a BACHD Mouse Modulates Steady-State Levels of Mutant Huntingtin Protein But Is Not Necessary for Production of a 586 Amino Acid Proteolytic Fragment The Journal of neuroscience : the official journal of the Society for Neuroscience, 2012; 32(22): 7454-7465.

Jiang Mali, Wang Jiawei, Fu Jinrong, Du Lin, Jeong Hyunkyung, West Tim, Xiang Lan, Peng Qi, Hou Zhipeng, Cai Huan, Seredenina Tamara, Arbez Nicolas, Zhu Shanshan, Sommers Katherine, Qian Jennifer, Zhang Jiangyang, Mori Susumu, Yang X William, Tamashiro Kellie L K, Aja Susan, Moran Timothy H, Luthi-Carter Ruth, Martin Bronwen, Maudsley Stuart, Mattson Mark P, Cichewicz Robert H, Ross Christopher A, Holtzman David M, Krainc Dimitri, Duan Wenzhen   Neuroprotective role of Sirt1 in mammalian models of Huntington's disease through activation of multiple Sirt1 targets Nature medicine, 2012; 18(1): 153-8.

Miller Jason, Arrasate Montserrat, Brooks Elizabeth, Libeu Clare Peters, Legleiter Justin, Hatters Danny, Curtis Jessica, Cheung Kenneth, Krishnan Preethi, Mitra Siddhartha, Widjaja Kartika, Shaby Benjamin A, Lotz Gregor P, Newhouse Yvonne, Mitchell Emily J, Osmand Alex, Gray Michelle, Thulasiramin Vanitha, Saudou Frédéric, Segal Mark, Yang X William, Masliah Eliezer, Thompson Leslie M, Muchowski Paul J, Weisgraber Karl H, Finkbeiner Steven   Identifying polyglutamine protein species in situ that best predict neurodegeneration Nature chemical biology, 2011; 7(12): 925-34.

Greiner Erin R, Yang X William   Huntington's disease: flipping a switch on huntingtin Nature chemical biology, 2011; 7(7): 412-4.

Tao Jifang, Wu Hao, Lin Quan, Wei Weizheng, Lu Xiao-Hong, Cantle Jeffrey P, Ao Yan, Olsen Richard W, Yang X William, Mody Istvan, Sofroniew Michael V, Sun Yi E   Deletion of astroglial Dicer causes non-cell-autonomous neuronal dysfunction and degeneration The Journal of neuroscience : the official journal of the Society for Neuroscience, 2011; 31(22): 8306-19.

Wilburn Brian, Rudnicki Dobrila D, Zhao Jing, Weitz Tara Murphy, Cheng Yin, Gu Xiaofeng, Greiner Erin, Park Chang Sin, Wang Nan, Sopher Bryce L, La Spada Albert R, Osmand Alex, Margolis Russell L, Sun Yi E, Yang X William   An antisense CAG repeat transcript at JPH3 locus mediates expanded polyglutamine protein toxicity in Huntington's disease-like 2 mice Neuron, 2011; 70(3): 427-40.

Yang X William, Lu Xiao-Hong   Molecular and cellular basis of obsessive-compulsive disorder-like behaviors: emerging view from mouse models Current opinion in neurology, 2011; 24(2): 114-8.

André Véronique M, Cepeda Carlos, Fisher Yvette E, Huynh My, Bardakjian Nora, Singh Sumedha, Yang X William, Levine Michael S   Differential electrophysiological changes in striatal output neurons in Huntington's disease The Journal of neuroscience : the official journal of the Society for Neuroscience, 2011; 31(4): 1170-82.

Graham Rona K, Deng Yu, Carroll Jeffery, Vaid Kuljeet, Cowan Catherine, Pouladi Mahmoud A, Metzler Martina, Bissada Nagat, Wang Lili, Faull Richard L M, Gray Michelle, Yang X William, Raymond Lynn A, Hayden Michael R   Cleavage at the 586 amino acid caspase-6 site in mutant huntingtin influences caspase-6 activation in vivo The Journal of neuroscience : the official journal of the Society for Neuroscience, 2010; 30(45): 15019-29.

Pouladi Mahmoud A, Xie Yuanyun, Skotte Niels Henning, Ehrnhoefer Dagmar E, Graham Rona K, Kim Jeong Eun, Bissada Nagat, Yang X William, Paganetti Paolo, Friedlander Robert M, Leavitt Blair R, Hayden Michael R   Full-length huntingtin levels modulate body weight by influencing insulin-like growth factor 1 expression Human molecular genetics, 2010; 19(8): 1528-38.

Gu Xiaofeng, Greiner Erin R, Mishra Rakesh, Kodali Ravindra, Osmand Alex, Finkbeiner Steven, Steffan Joan S, Thompson Leslie Michels, Wetzel Ronald, Yang X William   Serines 13 and 16 are critical determinants of full-length human mutant huntingtin induced disease pathogenesis in HD mice Neuron, 2009; 64(6): 828-40.

Menalled Liliana, El-Khodor Bassem F, Patry Monica, Suárez-Fariñas Mayte, Orenstein Samantha J, Zahasky Benjamin, Leahy Christina, Wheeler Vanessa, Yang X William, MacDonald Marcy, Morton A Jennifer, Bates Gill, Leeds Janet, Park Larry, Howland David, Signer Ethan, Tobin Allan, Brunner Daniela   Systematic behavioral evaluation of Huntington's disease transgenic and knock-in mouse models Neurobiology of disease, 2009; 35(3): 319-36.

Hutnick Leah K, Golshani Peyman, Namihira Masakasu, Xue Zhigang, Matynia Anna, Yang X William, Silva Alcino J, Schweizer Felix E, Fan Guoping   DNA hypomethylation restricted to the murine forebrain induces cortical degeneration and impairs postnatal neuronal maturation Human molecular genetics, 2009; 18(15): 2875-88.

Lu Xiao-Hong, Fleming Sheila M, Meurers Bernhard, Ackerson Larry C, Mortazavi Farzad, Lo Victor, Hernandez Daniela, Sulzer David, Jackson George R, Maidment Nigel T, Chesselet Marie-Francoise, Yang X William   Bacterial artificial chromosome transgenic mice expressing a truncated mutant parkin exhibit age-dependent hypokinetic motor deficits, dopaminergic neuron degeneration, and accumulation of proteinase K-resistant alpha-synuclein The Journal of neuroscience : the official journal of the Society for Neuroscience, 2009; 29(7): 1962-76.

Spampanato J, Gu X, Yang X W, Mody I   Progressive synaptic pathology of motor cortical neurons in a BAC transgenic mouse model of Huntington's disease Neuroscience, 2008; 157(3): 606-20.

Lobo Mary Kay, Yeh Christopher, Yang X William   Pivotal role of early B-cell factor 1 in development of striatonigral medium spiny neurons in the matrix compartment Journal of neuroscience research, 2008; 86(10): 2134-46.

Gray Michelle, Shirasaki Dyna I, Cepeda Carlos, André Véronique M, Wilburn Brian, Lu Xiao-Hong, Tao Jifang, Yamazaki Irene, Li Shi-Hua, Sun Yi E, Li Xiao-Jiang, Levine Michael S, Yang X William   Full-length human mutant huntingtin with a stable polyglutamine repeat can elicit progressive and selective neuropathogenesis in BACHD mice The Journal of neuroscience : the official journal of the Society for Neuroscience, 2008; 28(24): 6182-95.

Lobo Mary Kay, Cui Yijun, Ostlund Sean B, Balleine Bernard W, Yang X William   Genetic control of instrumental conditioning by striatopallidal neuron-specific S1P receptor Gpr6 Nature neuroscience, 2007; 10(11): 1395-7.

Gu Xiaofeng, André Véronique M, Cepeda Carlos, Li Shi-Hua, Li Xiao-Jiang, Levine Michael S, Yang X William   Pathological cell-cell interactions are necessary for striatal pathogenesis in a conditional mouse model of Huntington's disease Molecular neurodegeneration, 2007; 2(11): 8.

Yang Zhongan, Jiang Hong, Chachainasakul Thawinee, Gong Shiaoching, Yang Xiangdong William, Heintz Nathaniel, Lin Shuo   Modified bacterial artificial chromosomes for zebrafish transgenesis Methods (San Diego, Calif.), 2006; 39(3): 183-8.

Lobo Mary Kay, Karsten Stanislav L, Gray Michelle, Geschwind Daniel H, Yang X William   FACS-array profiling of striatal projection neuron subtypes in juvenile and adult mouse brains Nature neuroscience, 2006; 9(3): 443-52.

Yang X William, Gong Shiaoching   An overview on the generation of BAC transgenic mice for neuroscience research Current protocols in neuroscience / editorial board, Jacqueline N. Crawley ... [et al.], 2005; Chapter 5(3): Unit 5.20.

Gong Shiaoching, Yang X William   Modification of bacterial artificial chromosomes (BACs) and preparation of intact BAC DNA for generation of transgenic mice Current protocols in neuroscience / editorial board, Jacqueline N. Crawley ... [et al.], 2005; Chapter 5(3): Unit 5.21.

Gu Xiaofeng, Li Chenjian, Wei Weizheng, Lo Victor, Gong Shiaoching, Li Shi-Hua, Iwasato Takuji, Itohara Shigeyoshi, Li Xiao-Jiang, Mody Istvan, Heintz Nathaniel, Yang X William   Pathological cell-cell interactions elicited by a neuropathogenic form of mutant Huntingtin contribute to cortical pathogenesis in HD mice Neuron, 2005; 46(3): 433-44.

Gong Shiaoching, Yang Xiangdong William, Li Chenjian, Heintz Nathaniel   Highly efficient modification of bacterial artificial chromosomes (BACs) using novel shuttle vectors containing the R6Kgamma origin of replication Genome research, 2002; 12(12): 1992-8.

Yang X W, Wynder C, Doughty M L, Heintz N   BAC-mediated gene-dosage analysis reveals a role for Zipro1 (Ru49/Zfp38) in progenitor cell proliferation in cerebellum and skin Nature genetics, 1999; 22(4): 327-35.

Yang X W, Model P, Heintz N   Homologous recombination based modification in Escherichia coli and germline transmission in transgenic mice of a bacterial artificial chromosome Nature biotechnology, 1997; 15(9): 859-65.

Yang X W, Zhong R, Heintz N   Granule cell specification in the developing mouse brain as defined by expression of the zinc finger transcription factor RU49 Development (Cambridge, England), 1996; 122(2): 555-66.

Baserga S J, Gilmore-Hebert M, Yang X W   Distinct molecular signals for nuclear import of the nucleolar snRNA, U3 Genes & development, 1992; 6(6): 1120-30.

Baserga S J, Yang X D, Steitz J A   Three pseudogenes for human U13 snRNA belong to class III Gene, 1991; 107(2): 347-8.

Baserga S J, Yang X D, Steitz J A   An intact Box C sequence in the U3 snRNA is required for binding of fibrillarin, the protein common to the major family of nucleolar snRNPs The EMBO journal, 1991; 10(9): 2645-51.