Institute for Advanced Study

Aaron Ciechanover Workshop on Nobel Laureate in Chemistry Technion - Israel Institute of Technology Visiting Member, HKUST Institute for Advanced Study System and Michael Karin University of California at San Diego Pathogenesis of Diseases Ron Kopito Stanford University Brenda Schulman 18 - 22 January 2010 (Mon - Fri) St Jude’s Children Research Hospital

Lectures 9:00 am - 12:00 noon Seminars 2:00 pm - 3:30 pm Sze-Yuen Chung Council Chamber (7/F via Lifts 13-15) Padma and Hari Harilela Lecture Theater (LT-C) 18 Jan “The Ubiquitin Proteolytic System: Historical Overview, “On the Regulation of the Regulators or How the (Mon) Mechanisms of Action, Involvement in Human Diseases, Ubiquitin System Components are Degraded” and Drug Targeting” by Aaron Ciechanover by Aaron Ciechanover 19 Jan “Structural Biology of the Ubiquitin System: Getting “Dynamic Mechanisms of Ubiquitin Conjugation” (Tue) Ubiquitin onto Targets” by Brenda Schulman by Brenda Schulman 20 Jan “Structural Biology of the Ubiquitin System: After “Dissection of the Endoplasmic Reticulum Associated (Wed) Ubiquitination” by Brenda Schulman Degradation (ERAD) System in Mammalian Cells” “Human Diseases and Drug Targeting of the Ubiquitin by Ron Kopito System” by Aaron Ciechanover 21 Jan “ Quality Control and the Ubiquitin Proteasome “Impaired Function of the Ubiquitin-Proteasome (Thu) System in Neurodegenerative Disease” by Ron Kopito Pathway in Huntington’s Disease” by Ron Kopito 22 Jan “The Regulation of NF-␬B by Protein Ubiquitination: “Differential TRAF3 Ubiquitination Determines the (Fri) From to Biology” by Michael Karin Outcome of TLR Signaling” by Michael Karin

Enquiries: [email protected]/2358 8424 Co-organized with 3437 Department of Biochemistry and PTC-G1 http://ias.ust.hk Molecular Neuroscience Center Institute for Advanced Study Seminars

Ubiquitin System and Pathogenesis of Diseases

18 – 22 January 2010 2:00 – 3:30 pm Padma and Hari Harilela Lecture Theater (LT-C), HKUST

18 Jan (Mon) “On the Regulation of the Regulators or How the Ubiquitin System Components are Degraded”

Dr. Aaron Ciechanover (Nobel Laureate in Chemistry) Technion – Israel Institute of Technology

Aaron Ciechanover was born in Haifa, Israel in 1947. He is a Distinguished Research Professor in the Technion - Israel Institute of Technology in Haifa. He received his M.Sc. (1971) and M.D. (1975) from the Hebrew University in Jerusalem, and his D.Sc. (1982) from the Technion. There, as a graduate student with Dr. Avram Hershko and in collaboration with Dr. Irwin A. Rose from the Fox Chase Cancer Center in Philadelphia, they discovered that covalent attachment of ubiquitin to a target protein signals it for degradation. They deciphered the mechanism of conjugation, described the general proteolytic functions of the system, and proposed a model according to which this modification serves as a recognition signal for a specific downstream protease. As a post doctoral fellow with Dr. Harvey Lodish at the M.I.T., he continued his studies on the ubiquitin system and made additional important discoveries. Along the years it has become clear that ubiquitin-mediated proteolysis plays major roles in numerous cellular processes, and aberrations in the system underlie the pathogenetic mechanisms of many diseases, among them certain malignancies and neurodegenerative disorders. Consequently, the system has become an important platform for drug development. Among the numerous prizes Ciechanover received are the 2000 Albert Lasker Award, the 2003 Israel Prize, and the 2004 Nobel Prize (Chemistry; shared with Drs. Hershko and Rose). Among many esteemed bodies, Ciechanover is member of the Israeli Academy of Sciences and Humanities, the USA National Academy of Sciences and its Institute of Medicine (Foreign Associate), the American Philosophical Society, and the American Academy of Arts and Sciences (Foreign Fellow). IAS Seminars Ubiquitin System and Pathogenesis of Diseases

19 Jan (Tue) “Dynamic Mechanisms of Ubiquitin Conjugation” Brenda Schulman St Jude Children’s Research Hospital

Brenda Schulman is an Investigator of the Howard Hughes Medical Institute, and a Full Member in the Departments of Structural Biology and Genetics/Tumor Cell Biology at St. Jude Children’s Research Hospital. She is also Co-Director of the Program in Molecular Oncology at the St. Jude Cancer Center, and holds affiliate faculty positions at the University of Tennessee College of Medicine and Vanderbilt University. Schulman received her bachelor’s degree in Biology from the in 1989. Following obtaining her Ph.D. in Biology from M.I.T. in 1996, she did postdoctoral studies in cell cycle research at Massachusetts General Hospital, and in X-ray crystallography at Memorial Sloan-Kettering Cancer Center. She has received a Pew Scholar Award in the Biomedical Sciences, a Beckman Young Investigator Award, and a U.S. Presidential Early Career Award for Scientists and Engineers. Her current research is focused on understanding the conjugation pathways for ubiquitin and ubiquitin-like , and on the roles of these pathways in controlling cell division.

20 & 21 Jan (Wed & Thu) “Dissection of the Endoplasmic Reticulum Associated Degradation (ERAD) System in Mammalian Cells” “Impaired Function of the Ubiquitin-Proteasome Pathway in Huntington’s Disease” Ron Kopito Stanford University

Ron R. Kopito received his A.B. from Bowdoin College in 1976 and his Ph.D. from the Massachusetts Institute of Technology (MIT) in 1982. He was a Postdoctoral Fellow with Harvey Lodish at the Whitehead Institute at MIT from 1982-1987. Since 1987 he has been on the faculty of Stanford University where is currently a Professor in the Department of Biology. His is a recipient of many awards, including appointments as a Lucille P. Markey Scholar (1985-1991) a Presidential Young Investigator (1989-1994) an Established Investigator of the American Heart Association. He has served or is serving on the editorial boards of the Journal of Biological Chemistry, the Journal of Cell Sciences, the Journal of Membrane Biology and Autophagy. Research in Professor Kopito’s lab is focused on understanding the cellular ‘quality control’ mechanisms that monitor protein folding and assembly in mammalian cells, and the role of these processes in the prevention of human disease. IAS Seminars Ubiquitin System and Pathogenesis of Diseases

22 Jan (Fri) “Differential TRAF3 Ubiquitination Determines the Outcome of TLR Signaling” Michael Karin University of California at San Diego

Michael Karin received his BSc in Biology in 1975 at Tel Aviv University, Tel Aviv, Israel and his PhD in Molecular Biology in 1979, University of California, Los Angeles. Dr. Karin is currently a Distinguished Professor of Pharmacology and Pathology at the School of Medicine, University of California, San Diego, where has been on the faculty since 1987. He was a cofounder of Signal Pharmaceutical (currently Celgene) and had served as a member of the Scientific Advisory Board of the Signal Research Division of Celgene. Dr. Karin also served as a member of the National Advisory Council for Environmental Health Sciences and has been an American Cancer Society Research Professor since 1999 and a member of the US National Academy of Sciences since 2005. He is a leading world authority on signal transduction pathways that regulate gene expression in response to extracellular stimuli, infection and stress. Key achievements include definition of cis elements that mediate gene induction by hormones, cytokines and stress, identification and characterization of the transcription factors that recognize these elements and the protein kinase cascades that regulate their activities. Much of Dr. Karin’s current activity is focused on understanding the link between inflammation, cancer and metabolic disease as well as on understanding the signaling mechanisms used by receptors involved in inflammation (TNF receptors) and innate immunity (TLR2 and NLRs). He has published over 300 scientific articles and is an inventor on over 25 different patents or pending patent applications. Recently, Dr Karin was ranked first worldwide by the Institute of Scientific Information (ISI) in a recent listing of most-cited molecular biology and genetic research papers published in prestigious journals.