2015 Canada Gairdner Recipients’ Lecture University of Toronto – Macleod Auditorium Thursday, October 29, 2015; 9:00 am – 3:00 pm

Thursday, October 30, 2014 Time Sessions and presentations’ Speakers titles 9:00 am – 9:05 am (5 mins) Opening Session – Welcome Dr. John Dirks, Remarks President & Scientific Director The Gairdner Foundation

9:05 am – 9:10 am (5 mins) Chairs & Dean’s Remarks Dr. Trevor Young, Dean, Faculty of Medicine University of Toronto

2015 Canada Gairdner Recipients’ Lectures

9:10 am - 9:45am (35mins) “Lessons from yeast – Molecular Dr. , Machinery of autophagy” 2015 Canada Gairdner International Laureate Tokyo Institute of Technology, Yokohama, Japan

9:45am – 10:20am (35 mins) “P1 3-Kinase and human disease” Dr. Lewis Cantley, 2015 Canada Gairdner International Laureate Weill Cornell Medical College, New York, NY, USA

10:20 am – 10:40 am (20 mins) Health Break

10:40 am -11: 15 am (35 mins) “TOR signaling in growth and Dr. Michael Hall, metabolism” 2015 Canada Gairdner International Laureate University of Basel, Basel, Switzerland

11:15 am-11:50 am (35 mins) “Regulatory T cells, a key controller Dr. Shimon Sakaguchi, of immune responses” 2015 Canada Gairdner International Laureate Osaka University, Osaka, Japan

11:50 am- 1:00 pm (by invitation only) Lunch/Networking

1:00 pm – 1:05 pm (5 mins) Introduction of speakers 1.05 pm – 1.40 pm (35 mins) “Nonsense-mediated mRNA decay Dr. Lynne Maquat, 2015 Canada Gairdner Recipients’ Lecture University of Toronto – Macleod Auditorium Thursday, October 29, 2015; 9:00 am – 3:00 pm

and human disease: Genome 2015 Canada Gairdner International guardian and executor” Laureate, University of Rochester, Rochester, NY, USA

1:40 pm - 2:15 pm (35 mins) “Making the blastocyst – from cells to Dr. Janet Rossant, genes to stem cells” 2015 Canada Gairdner Wightman Laureate, The Hospital for Sick Children, Toronto, ON

2:15 pm - 2:50 pm (35mins) “Lessons from Ebola and AIDS for Dr. Peter Piot, global health” 2015 Canada Gairdner Global Health Laureate, Director, London School of Hygiene & Tropical Medicine, London, UK

2:50 pm – 3:00 pm (10 mins) Closing Remarks Dr. John Dirks, President & Scientific Director, The Gairdner Foundation

2015 Gairdner Symposium “RNA and The New Genetics” University of Toronto – MacLeod Auditorium Friday, October 30, 2015 – 8.45 a.m. – 3.30 p.m.

Friday, October 30, 2015 Time Sessions and Research overview Speakers presentations’ titles 8:45 am – 8:55 am Opening Session – Dr. John Dirks, M.D., Welcome Remarks President and Scientific Director The Gairdner Foundation

8:55 am – 9:10 am General introduction about Made seminal contributions Dr. Lynne Maquat, Ph.D., non-coding RNAs and on mechanisms of nonsense- Director of the Center for RNA ethical issues of genome mediated messenger RNA Biology: From Genome to editing manipulation in decay (NMD) and another Therapeutics, and Professor of human embryo. pathway she discovered and Biochemistry and Biophysics, named Staufen-mediated University of Rochester School of mRNA decay (SMD). Medicine and Dentistry, J. Lowell Orbison Endowed Chair; 2015 Canada Gairdner International Awardee

Noncoding RNA

9:10 am – 9:40 am The origins and functions Dr. Phillip Sharp, Ph.D., of non-coding RNAs. Institute Professor Koch Institute for Integrative Cancer Research, MIT; Gairdner awardee; Nobel Laureate in Physiology or Medicine

9:40 am – 10:10 am Genome regulation by Describes long noncoding Dr. Howard Chang, M.D., Ph.D., noncoding RNAs. RNAs are key players in the Professor of Dermatology development of disease. Director, Center for Personal Dynamic Regulomes; School of Medicine

10:10 am – 10:30 am Health Break RNA-mediated Epigenetics

2015 Gairdner Symposium “RNA and The New Genetics” University of Toronto – MacLeod Auditorium Friday, October 30, 2015 – 8.45 a.m. – 3.30 p.m.

10:30 am – 11:00 am Regulatory interactions Characterizes long Dr. Jeannie Lee, M.D., Ph.D., between long noncoding noncoding RNA-mediated Professor of Genetics and Pathology RNA and epigenetic epigenetic regulation, Harvard Medical School, complexes. including X-chromosome Massachusetts General Hospital inactivation. Investigator, HHMI

Pre-mRNA Splicing 11:00 am – 11:30 am Alternative splicing Made pioneering Dr. Benjamin Blencowe, Ph.D., regulatory networks and contributions to the discovery Professor their roles in and characterization of Banbury Chair in Medical Research neurodevelopmental alternative splicing Department of Molecular Genetics; disorders regulatory networks and is University of Toronto currently focusing on the role of these networks in the control of cell fate and neurological disorders.

microRNAs 11:30 am – 12:00 pm New mechanisms of Investigates the regulation Dr. Joshua Mendell, M.D., Ph.D., noncoding RNA regulation and function of microRNAs, Professor of Molecular Biology and function. with a focus on potentially Member, Center for Regenerative important roles for Science and Medicine microRNAs in normal Member, Simmons Cancer Center physiology and in the UT Southwestern Medical Center development of cancer. Investigator, HHMI

12:00 pm – 1:00 pm Lunch/Networking CRISPR/Cas

1:00 pm – 1:30 pm Biology, mechanisms and Characterizes gene Dr. , Ph.D., applications of CRISPR- regulatory mechanisms in Professor and Departmental Head Cas9: a game changer in infection and immunity, Regulation in Infection Biology genome engineering. including Cas9 as a powerful Hannover Medical School Helmholtz tool for genome editing. Centre for Infection Research Braunschweig, Germany

1:30 pm – 2:00 pm Development of CRISPR- Develops molecular Dr. , Ph.D., Cas9 for Genome technologies for controlling Core Member Engineering cellular function, including Broad Institute of MIT and Harvard harnessing CRISPR-Cas as a Investigator new genome-editing tool for McGovern Institute for Brain eukaryotic cells Research W. M. Keck Career Development 2015 Gairdner Symposium “RNA and The New Genetics” University of Toronto – MacLeod Auditorium Friday, October 30, 2015 – 8.45 a.m. – 3.30 p.m.

Professor Departments of Brain and Cognitive Sciences and Biological Engineering; MIT

2:00 pm – 2:20 pm Health break Commentary 2:20 pm – 2:50 pm The Science, Safety, and Investigates RNA-based gene Dr. Erik Sontheimer, Ph.D., Ethics of Genome Editing regulation biology and Professor at the RNA Therapeutics mechanisms; CRISPR Institute interference; RNA-directed University of Massachusetts Medical genome editing and gene School control

2:50 pm – 3:20 pm Round table Discussion All speakers + Dr. Lynne Maquat 3:20 pm – 3:30 pm Closing Remarks Dr. John Dirks, M.D., President and Scientific Director The Gairdner Foundation

1. A world leader of research in molecular biology and biochemistry, Dr. Phillip A. Sharp is Institute Professor at the Massachusetts Institute of Technology. Much of Dr. Sharp's scientific work has been conducted at MIT's Center for Cancer Research (now the Koch Institute), which he joined in 1974 and directed from 1985 to 1991. He subsequently led the Department of Biology from 1991 to 1999 before assuming the directorship of the McGovern Institute from 2000-2004. His research interests have centered on the molecular biology of gene expression relevant to cancer and the mechanisms of RNA splicing. His landmark achievement was the discovery of RNA splicing in 1977. This work provided one of the first indications of the startling phenomenon of “discontinuous genes” in mammalian cells. The discovery that genes contain nonsense segments that are edited out by cells in the course of utilizing genetic information is important in understanding the genetic causes of cancer and other diseases. This discovery, which fundamentally changed scientists' understanding of the structure of genes, earned Dr. Sharp the 1993Nobel Prize in Physiology or Medicine. His lab has now turned its attention to understanding how RNA molecules act as switches to turn genes on and off (RNA interference). These newly discovered processes have 2015 Gairdner Symposium “RNA and The New Genetics” University of Toronto – MacLeod Auditorium Friday, October 30, 2015 – 8.45 a.m. – 3.30 p.m.

revolutionized cell biology and could potentially generate a new class of therapeutics. Dr. Sharp has authored over 385 scientific papers. He has received numerous awards and honorary degrees, and has served on many advisory boards for the government, academic institutions, scientific societies, and companies. His awards include the Gairdner Foundation International Award, General Motors Research Foundation Alfred P. Sloan, Jr. Prize for Cancer Research, the Albert Lasker Basic Medical Research Award, the National Medal of Science and the inaugural Double Helix Medal from CSHL. He is an elected member of the National Academy of Sciences, the Institute of Medicine, the American Academy of Arts and Sciences, the American Philosophical Society, and is a Foreign Fellow of the Royal Society, UK. A native of Kentucky, Dr. Sharp earned a B.A. degree from Union College, KY in 1966, and a PhD in chemistry from the University of Illinois, Champaign-Urbana in 1969. He did his postdoctoral training at the California Institute of Technology, where he studied the molecular biology of plasmids from bacteria in Professor Norman Davidson's laboratory. Prior to joining MIT, he was Senior Scientist at Cold Spring Harbor Laboratory. In 1978 Dr. Sharp co-founded Biogen (now Biogen Idec) and in 2002 he co-founded Alnylam Pharmaceuticals, an early-stage therapeutics company.

2. Howard Y. Chang M.D., Ph.D. is Professor of Dermatology and Director of the

Center for Personal Dynamic Regulomes at Stanford University School of

Medicine. Chang earned a Ph.D. in Biology from MIT, M.D. from Harvard Medical

School, and completed Dermatology residency and postdoctoral training at

Stanford University. His research addresses how large sets of genes are turned

on or off together, which is important in normal development, cancer, and aging.

Chang discovered a new class of genes, termed long noncoding RNAs, can

control gene activity throughout the genome, illuminating a new layer of biological

regulation. He has invented new methods for defining the shapes of RNA and 2015 Gairdner Symposium “RNA and The New Genetics” University of Toronto – MacLeod Auditorium Friday, October 30, 2015 – 8.45 a.m. – 3.30 p.m.

DNA genome-wide. The long term goal of his research is to decipher the

regulatory information in the genome to benefit human health.

Dr. Chang’s honors include the Damon Runyon Scholar Award, American

Cancer Society Research Scholar Award, California Institute for Regenerative

Medicine New Faculty Award, elected membership to the American Society for

Clinical Investigation, the Vilcek Prize for Creative Promise, Howard Hughes

Medical Institute Early Career Scientist, and the Judson Daland Prize of the

American Philosophical Society.

3. Dr. Jeannie Lee

4. Dr. Benjamin Blencowe is internationally recognized for his contributions to the understanding of splicing regulation. His research group has pioneered methods for the genome-wide discovery and characterization of alternative splicing events. This work has contributed fundamental insights into the cis-regulatory code and trans-acting factors that govern splice site selection, and has led to the discovery of splicing switches that control transcriptional networks with critical roles in mammalian development. His group is currently engaged in the systematic analysis of the regulation, function and evolution of alternative exon networks, with a focus on exon networks that control nervous system development and embryonic stem cell pluripotency.

5. Dr. Joshua Mendell attained his undergraduate degree in Biology at Cornell University in 1996 and completed an M.D.-Ph.D degree at the Johns Hopkins School of Medicine in 2003. In 2004, Dr. Mendell established a research group at Johns Hopkins focused on the regulation and function of noncoding RNAs in normal physiology and in diseases such as cancer. In particular, the Mendell laboratory has devoted significant effort towards elucidating functions of the microRNA (miRNA) pathway. The Mendell research group has been at the forefront of defining miRNA functions in normal physiology and in cancer in vivo. Dr. Mendell’s research group provided one of the first demonstrations that miRNAs function as components of critical oncogenic and tumor suppressor pathways and that miRNAs represent potent and non-toxic anti-cancer therapeutic agents when delivered systemically. Dr. Mendell has been the recipient of several awards including being named the Outstanding Young 2015 Gairdner Symposium “RNA and The New Genetics” University of Toronto – MacLeod Auditorium Friday, October 30, 2015 – 8.45 a.m. – 3.30 p.m.

Scientist in the State of Maryland in 2007 and a HHMI Early Career Scientist in 2009. In 2010, Dr. Mendell received the AACR Award for Outstanding Achievement in Cancer Research. In 2011, Dr. Mendell received a Rising Stars Award from the Cancer Prevention and Research Institute of Texas and relocated his laboratory to UT Southwestern Medical Center in Dallas where he is currently a Professor of Molecular Biology.

6. Emmanuelle Charpentier studied biochemistry and microbiology at the University Pierre and Marie Curie, Paris, France and received her PhD in Microbiology for her research performed at the Pasteur Institute. She then moved to the , where she held Research Associate positions at the Rockefeller University, New York University Langone Medical Center and the Skirball Institute of Biomolecular Medicine (all in New York, NY) and at St Jude Children’s Research Hospital (in Memphis, TN). Emmanuelle Charpentier returned to Europe to establish her own research group at the Max F. Perutz Laboratories of the University of Vienna in Austria where she habilitated in the field of Microbiology. She was then recruited as an Associate Professor at the Laboratory for Molecular Infection Medicine Sweden (MIMS, EMBL Partnership for Molecular Medicine) at Umeå University where she habilitated in the field of Medical Microbiology. In 2012, Emmanuelle Charpentier was appointed Professor at Hannover Medical School and Head of the Department “Regulation in Infection Biology” at the Helmholtz Centre for Infection Research in Germany. E. Charpentier is recognized as a world-leading expert in regulatory mechanisms underlying processes of infection and immunity in bacterial pathogens. With recent groundbreaking findings in the field of RNA-mediated regulation based on the CRISPR-Cas9 system, E. Charpentier has laid the foundation for the development of a novel, highly versatile and specific genome editing tool that is deemed capable of revolutionizing life sciences research and could open up whole new opportunities in biomedical gene therapies.

7. Feng Zhang is a core member of the Broad Institute of MIT and Harvard, as well as an investigator at the McGovern Institute for Brain Research at MIT and the W. M. Keck Career Development Professor at MIT with a joint appointment in the Departments of Brain and Cognitive Sciences and Biological Engineering. 2015 Gairdner Symposium “RNA and The New Genetics” University of Toronto – MacLeod Auditorium Friday, October 30, 2015 – 8.45 a.m. – 3.30 p.m.

Zhang seeks to understand the molecular machinery of brain cells through the development and application of innovative technologies. He created and is continuing to perfect tools that afford researchers precise control over biological activities occurring inside the cell. With these tools, researchers can deepen their understanding of how the genome works, and how it influences the development and function of the brain. Zhang also examines failures within the systems that cause disease.

Two different lines of fundamental research and technology development are helping him do that: and genome engineering. With his doctoral advisor and labmate at Stanford University, he developed optogenetics to study brain circuits, a technique in which light is used to affect signaling and gene expression of neurons involved in complex behaviors. In his own laboratory, Zhang developed the TALE and CRISPR-Cas9 systems to enable new, cheaper, and more effective ways to manipulate mammalian genomes. Although Zhang’s main area of focus is the brain, the potential applications of the CRISPR-Cas9 technology extend well beyond neuroscience.

In the interest of sharing CRISPR-Cas9 resources openly, Zhang’s team has already provided CRISPR reagents and tips to many researchers, and continues to make all of its CRISPR tools available. Since his team first described genome editing using CRISPR- Cas9 in January 2013, Zhang’s lab has fulfilled over 20,000 reagent requests from around the world, enabling researchers to make new discoveries in a broad spectrum of biological research fields.

Zhang is widely recognized for his pioneering work in optogenetics and genome editing. He has received many awards including the Perl/UNC Prize in Neuroscience for optogenetics (2012, shared with Karl Deisseroth and Edward Boyden), the National Science Foundation’s Alan T. Waterman Award (2014), the Jacob Heskel in Biotechnology and Medicine for CRISPR-Cas9 (2014, shared with Emmanuelle Charpentier and ). Zhang received his A.B. in chemistry and physics from Harvard College and his Ph.D. in chemistry from Stanford University, and he is grateful to all of his mentors for their training and guidance.

8. Erik J. Sontheimer, Ph.D., is Professor in the RNA Therapeutics Institute and the Program for Molecular Medicine at the University of Massachusetts Medical School. He received his Ph.D. in 1992 from Yale University, where he did his thesis work with Joan Steitz on pre-mRNA splicing mechanisms. He then did 2015 Gairdner Symposium “RNA and The New Genetics” University of Toronto – MacLeod Auditorium Friday, October 30, 2015 – 8.45 a.m. – 3.30 p.m.

postdoctoral work with Joe Piccirilli at the University of Chicago, where he was a Fellow of the Jane Coffin Childs Memorial Fund. In 1999, Sontheimer joined the faculty in the Department of Molecular Biosciences at Northwestern University, where he turned his attention to small RNA-based gene regulation in eukaryotes. In 2008 his laboratory also began working on genetic interference in bacteria. Among other advances, they provided the first demonstration that small RNAs known as CRISPR RNAs can target DNA molecules directly, paving the way for the development of RNA-guided genome engineering. While at Northwestern, he received a CAREER Award from the National Science Foundation, a New Investigator Award from the Burroughs Wellcome Fund, a Distinguished Teaching Award, and the Nestlé Award from the American Society for Microbiology. In 2014 he moved to the RNA Therapeutics Institute at UMass Medical School, where he is continuing his research on the fundamental roles of RNA molecules, and on the uses of RNAs in biomedical research and disease treatment.