X. William Yang

X. William Yang *


Work Address:
695 Charles Young Drive, #3309
Los Angeles, CA 90095 695 Charles Young Drive, Gonda 3506B
Los Angeles, CA 90095\

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Professor, Psychiatry and Biobehavioral Sciences


Research Interests

My laboratory is interested in using the mouse molecular genetic approach to study the pathogenesis of neurodegenerative diseases. One recurring theme in neurodegenerative diseases is that a widely expressed mutant protein can cause highly selective degeneration of a subset of neurons. The pathogenesis of such selective neurodegeneration remains unclear. Currently, we are focusing on Huntington’s disease (HD) to study the molecular and cellular mechanisms underlying the selective degeneration of the striatal and cortical neurons in the disease. It remains unclear whether the selective neurodegeneration in HD is primarily due to toxicities of mutant Huntingtin (Ht) within the vulnerable neurons (the suicide model) or secondary to dysfunction or degeneration of other neurons or glia (the murder model), or due to both toxicities (assisted suicide model). To address this question, we have developed two conditional mouse models of HD. In the first model, expression of mutant Ht exon1 can be activated by Cre-mediated recombination. By using different mouse Cre lines, we have developed an allelic series of HD mouse models with mHt expression is activated in the cortical neurons only, striatal neurons only, or throughout the entire CNS. These models will allow us to understand whether cell-autonomous or non-cell autonomous toxicites of mHt is required for the dysfunction and degneration of the most vulnerable cortical and striatal neurons. In addition to the conditional activation model, we have also generated a full length conditional inactivation model of HD using Bacterial Artificial Chromosome (BAC)- mediated transgenesis. BACs are large cloned genomic DNA (average size 180-200kb) and our previous work has demonstrated that BAC transgenes can consistently confer high level, and endogenous-like gene expression in vivo. In this BAC transgenic model of HD, full length mutant Ht expression can be conditionally inactivated by Cre-mediated recombination. Using these two conditional HD models, we are particularly interested in addressing the hypothesis that non-cell autonomous toxicities of mHt is necessary and perhaps sufficient to cause selective degeneration of striatal and cortical neurons in HD. Another research interest in my laboratory is to applly the BAC modification and BAC transgenic technology to develop mouse models for Parkinson’s disease (PD). Currently we are using the BACs to overexpress PD-related mutant proteins in the mouse brain. In the long run, my laboratory will use these novel mouse model systems to systematically study key pathogenic mechanisms and to test therapeutic strategies for these devastating neurodegenerative diseases.



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.


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