Huntington's Disease

Dr. X. William Yang completed his B.S./M.S. degrees in Molecular Biophysics & Biochemistry at Yale University in 1991. He obtained M.D./Ph.D. training at Rockefeller University (Ph.D., 1998) and Weill Medical College of Cornell University (M.D., 2000). He co-invented the technology to engineer Bacterial Artificial Chromosomes (BACs) and to generate BAC transgenic mice. His laboratory at UCLA (established in 2002) pioneered the use of a BAC transgenic approach in mice to study pathogenesis of neurodegenerative disorders including Huntington’s disease, Parkinson’s disease, and Alzheimer’s disease. The Yang lab has also applied novel genetic and systems biology approaches to study molecular networks in healthy and disease brains, and to study brain-wide morphology of genetically-defined neurons. He is a recipient of BRAIN Initiative Awards from NIH, Brain Disorder Award from McKnight Foundation, the Leslie Gehry Brenner Prize for Innovation in Science in 2014, and is an elected member of the American Society for Clinical Investigation.Myriam Heiman and her lab use HD patient tissue, as well as mouse and cell models of HD to understand why some cells are more or less vulnerable to the mutant HD gene, and use knowledge of these intrinsic differences to identify new therapeutic targets for HD. Dr. Heiman has pioneered the use of in vivo genetic screening in the mammalian brain, as well as the use of novel single-cell and cell type-specific transcriptional profiling tools to study HD. Her work has recently pointed to the importance of neuronal innate immune activation and cell type-specific mitochondrial dysfunction in HD pathogenesis. Myriam is the recipient of several awards, including an Early Career Investigators Innovation Award from the Bumpus Foundation and a EUREKA grant from the National Institutes of Health. Dr. Thompson is a Donald Bren and Chancellor’s Professor in the Departments of Psychiatry and Human Behavior and Neurobiology and Behavior at the University of California Irvine. She has studied Huntington’s disease (HD) for most of her scientific career and was a member of the international consortium that identified the causative gene for HD in 1993. Since that time, the Thompson laboratory has been actively engaged in investigating the fundamental molecular and cellular events that underlie how the mutant HD gene causes degeneration of specific brain cell populations to induce motor and cognitive decline and premature death of patients with the ultimate goal to develop new treatments, including stem-cell based treatments. Dr. Thompson is the recipient of several awards including the HDF Lesley Gehry Brenner Award for Scientific Innovation in 2013, an NIH Research Program R35 Award and was elected an AAAS fellow in 2013.

• 1. Huntington’s Disease: Clinical Features, Genetic Diagnosis, and Brain ImagingCarlos Estevez-Fraga, Mitsuko Nakajima and Sarah J. Tabrizi2. Revolutionizing Clinical Research and Communication in Huntington’s Disease: The Huntington’s Disease Integrated Staging System (HD-ISS)Cristina Sampaio, Jeffrey D. Long, Alexandra Mansbach, Sarah J. Tabrizi, Emily C. Gantman3. Huntington’s Disease Genetics: Implications for PathogenesisMarcy E. Macdonald, Jong-Min Lee and James F. Gusella4. The Instability of the Huntington’s Disease CAG Repeat MutationVanessa C. Wheeler, Joseph C. Stone, Thomas H. Massey and Ricardo Mouro Pinto5. Mechanisms of Somatic CAG -Repeat Expansions in Huntington’s DiseaseAmit L. Deshmukh, Terence Gall-Duncan and Christopher E. Pearson6. RNA-Mediated Pathogenic Mechanisms in Huntington’s DiseaseGillian P. Bates, Sandra Fienko, Christian Landles and Aikaterini-Smaragdi Papadopoulou7. Huntingtin Protein-protein Interactions: From Biology to Therapeutic TargetsEduardo Silva Ramos, Todd M. Greco, Ileana M. Cristea and Erich E. Wanker8. Repeat-Associated Non-AUG (RAN) Translation and Huntington’s Disease: Pathology, Mechanistic and Therapeutic PerspectivesMonica Banez-Coronel, John Douglas Cleary and Laura P.W. Ranum9. Proteostasis Function and Dysfunction in Huntington’s DiseaseJuliana Abramovich, Korbin Kleczko, Vincent Masto and Judith Frydman10. Autophagy and Huntington’s DiseaseKatherine R. Croce, Hilary Grosso Jasutkar and Ai Yamamoto11. SUMO Modification in Huntington’s Disease: Unraveling Complex Mechanisms for Therapeutic InsightsCharlene Smith, Joan S. Steffan and Leslie M. Thompson12. Selective Vulnerability in Huntington’s Disease: From Excitotoxicity, MitochondrialDysfunction, and Transcription Dysregulation to Therapeutic OpportunityJacob S. Deyell, Ravinder Gulia and Albert R. La Spada13. Pathophysiology of Synapses and Circuits in Huntington DiseaseMarja D. Sepers, James Mackay and Lynn A. Raymond14. The Role of Glial Pathology in Huntington’s DiseaseSteven A. Goldman15. Systems Biology Study of Huntington’s DiseaseLeonardo E. Dionisio, Peter Langfelder, Jeffrey S. Aaronson, Jim Rosinski and X. William Yang16. Unbiased Genome-Wide Approaches to Identify Vulnerability Factors in Huntington’s DiseaseSuphinya Sathitloetsakun and Myriam Heiman17. Striatal Neuronal Models of Huntington’s Disease Via Direct Conversion: Modeling Age-dependent Disease PhenotypesYoung Mi Oh, Seong Won Lee and Andrew S. Yoo18. Genetic Mouse Models to Explore Huntington’s Disease Mechanisms and Therapeutic StrategiesMichelle Gray, Scott O. Zeitlin, Aida Moran-Reyna and Jeh-Ping Liu19. Huntington’s Disease: From Large Animal Models to HD Gene TherapySen Yan, Xiao-Jiang Li and Shihua Li20. Deep Learning and Deep Phenotyping of HD iPSCs: Applications to Study Biology and Test TherapeuticsSteven Finkbeiner21. The Promise of an Underappreciated Therapeutic Target: Sleep and Circadian Rhythm Dysfunction in Huntington’s DiseaseChristopher S. Colwell, Weiyi Tan and A. Jennifer Morton22. Huntingtin Lowering TherapeuticsNeil Aronin, Miguel E. Sena-Esteves, Anastasia Khvorova, Marian Difiglia and Michael Brodsky23. Gene Editing for HD: Therapeutic ProspectsRichard Z. Chen and Thomas F. Vogt24. Current Clinical Trials of New Therapeutic Agents for Huntington’s DiseaseBlair R. Leavitt

"Written by prominent leaders in the field, this is not only a must-read for clinicians and researchers of Huntington's disease, but also a highly valuable reference for people in neurodegenerative diseases field in general. The authors did an amazing job, with breadth and depth, in covering a wide range of critical aspects including genetics, molecular and cellular mechanisms of pathogenesis, pathology, patient symptoms and animal model phenotypes, and clinical trials. The literatures covered in this book include historical milestone discoveries as well as the most updated advances in research and therapeutic development. It is truly an indispensable resource for us." -- Chenjian Li, Research Fellow, Hoover Institution, Stanford University