PI3K Pathways in Immunology, Growth Disorders and Cancer

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1 PI3K Pathways in Immunology, Growth Disorders and Cancer January 19 23, 2017 Hilton Santa Fe Historic Plaza Hotel Santa Fe, New Mexico USA Scientific Organizers: Leon O. Murphy, Novartis Pharmaceuticals, USA Klaus Okkenhaug, Babraham Institute, UK Sabina C. Cosulich, AstraZeneca, UK The overall goal for this conference is to bring together scientific leaders and trainees with a common interest in PI3Ks and relevant downstream physiological processes. It will address advances in basic molecular and cellular mechanisms that are regulated by PI3Ks, other PI kinases and, their cognate phosphatases; highlight new advances in the characterization of PI3K pathway alterations in genetic syndromes that affect growth and the immune and nervous systems; and provide an important update on the clinical development of PI3K pathway inhibitors, and implications for the burgeoning field of cancer immunotherapy. Whole exome sequencing studies have increasingly implicated PI3K signaling in diseases (immune, growth and neurological disorders) which may benefit from drugs currently in development for cancer and inflammation. This conference will be an important forum for discussing approaches to treating these additional disorders. Session Topics: PI3K Function and Physiology PI3K Effectors Phosphatases Workshop 1: PI3K, Metabolism and Stress Pathways Class II/III PI3Ks Signaling from Non-Canonical PI Kinases Workshop 2: Career Development Overgrowth Syndromes PI3K in Immunity and Infection Workshop 3: PI3K in Immune Disorders and Immuno-Oncology PI3K and Oncology Discounted Registration Deadline: November 16, 2016 Note: Abstracts can still be submitted online for poster presentation. Upper image of lung cancer autophagy courtesy of NCI/ Massey Cancer Center at Virginia Commonwealth University Meeting Hashtag: #KSpi3k a 501(c)(3) nonprofit educational organization

2 THURSDAY, JANUARY 19 Arrival and Registration FRIDAY, JANUARY 20 PI3K Function and Physiology *Lewis C. Cantley, Weill Cornell Medicine, USA *Doreen A. Cantrell, University of Dundee, UK Len R. Stephens, Babraham Institute, UK Signaling via Class I PI3Ks Bart Vanhaesebroeck, University College London, Cancer Institute, UK Physiological Roles of PI3K Isoforms Matthias P. Wymann, University of Basel, Switzerland Complexity in PI3K Signaling and Targeting Jeffrey L. Kutok, Infinity Pharmaceuticals, USA The PI3K-gamma Inhibitor, IPI-549, Increases Antitumor Immunity by Targeting Tumor-Associated Myeloid Cells and Overcomes Immune Checkpoint Blockade Resistance in Preclinical Tumor Models John E. Burke, University of Victoria, Canada Short Talk: Conformational Disturbance of PI3Kdelta Regulation by Primary Immunodeficiency Mutations in PIK3CD and PIK3R1 Kyle A. Edgar, Genentech, Inc., USA Short Talk: The PI3K Inhibitor, Taselisib, has Enhanced Potency in PIK3CA Mutant Models Through a Unique Mechanism of Action PI3K Effectors *Sabina C. Cosulich, AstraZeneca, UK *Igor Vivanco, Institute of Cancer Research, UK Brendan D. Manning, Harvard School of Public Health, USA The TSC-Rheb-mTOR Circuit and Metabolic Control David A. Fruman, University of California, Irvine, USA The mtorc1/4e-bp/eif4e Axis in B-Cell Activation and Transformation John Blenis, Weill Cornell Medical College, USA mtorc1/s6k1: Regulation of RNA Biogenesis, Protein Synthesis and Cell Metabolism Ivan Yudushkin, Medical University of Vienna, Austria Short Talk: Membrane Subpopulations of mtorc2 Display Distinct Sensitivity to PI3K Poster Session 1 SATURDAY, JANUARY 21 Phosphatases *Len R. Stephens, Babraham Institute, UK *Brendan D. Manning, Harvard School of Public Health, USA Ramon Parsons, Icahn School of Medicine at Mount Sinai, USA PTEN Upstream, Instream and Downstream Lloyd Trotman, Cold Spring Harbor Laboratory, USA PTEN Function and Loss of Function in Prostate Metastasis Christina Anne Mitchell, Monash University, Australia New Roles for Inositol Polyphosphate Phosphatases Doreen A. Cantrell, University of Dundee, UK Phosphatidylinositol-3-Kinase Control of T Lymphocyte Differentiation: Dogma Versus Reality Ana Clara Carrera, Centro Nacional Biotechnologia/CSIC, Spain Short Talk: PI3K Depletion Induces Tumor Regression; E-Cadherin Downregulation Sensitizes PTEN-Mutant Tumors to PI3K-Beta Silencing Sarah Elizabeth Conduit, Monash University, Australia Short Talk: INPP5E Regulates Murine SHH Medulloblastoma Workshop 1: PI3K, Metabolism and Stress Pathways *Kyle A. Edgar, Genentech, Inc., USA *John E. Burke, University of Victoria, Canada Jack Flanagan, University of Auckland, New Zealand Evidence of a New Mechanism for Achieving PI3K Inhibition with Small Molecules via an Effect on Membrane Binding Thomas Leonard, Max F. Perutz Laboratories GmbH, Austria PI(3,4,5)P3 Allosterically Activates Akt Erika Ilagan, Harvard T.H. Chan School of Public Health, USA The TSC-Rheb-mTORC1 Circuit is a Shared Effector of PI3K-Akt and Ras-Erk Signaling Gina Lee, Weill Cornell Medicine, USA mtorc1-s6k1 Regulation of SR Protein Kinase Links mrna Biogenesis to De Novo Lipid Synthesis Marie H. Solheim, Joslin Diabetes Center, Harvard Medical School, USA Conserved p85alpha SH2 Domain Residues Play Differential Roles in p85alpha-irs-1 Binding Lukasz Pawel Magiera, University of Cambridge, UK Pik3ca Gain-of-Function Mutation Restricted to Mesenchymal Cells Expressing Fibroblast Activation Protein-Alpha Causes Skeletal Overgrowth Class II/III PI3Ks *Jonathan M. Backer, Albert Einstein College of Medicine, USA Volker Haucke, Leibniz Institut für Molekulare Pharmakologie, Germany Phosphoinositide Conversion in the Endolysosomal System Leon O. Murphy, Third Rock Ventures, USA Role of VPS34 in Cancer Growth and Autophagy Emilio Hirsch, Fondazione per la Ricerca Biomedica ONLUS, Italy Class II PI3K in Mitosis Wei-Xing Zong, Rutgers University, USA Short Talk: PI3-Kinase p110beta Regulates Cell Metabolism and Oncogenesis by Promoting Endocytic Turnover of Nutrient Transporters Poster Session 2 SUNDAY, JANUARY 22 Signaling from Non-Canonical PI Kinases *Bart Vanhaesebroeck, University College London, Cancer Institute, UK *Klaus Okkenhaug, Babraham Institute, UK Brooke M. Emerling, Sanford Burnham Prebys Medical Discovery Institute, USA PI5P4Ks and Cancer Metabolism

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4 Pietro V. De Camilli, Yale University School of Medicine, USA Phosphoinositide Dynamics at the Plasma Membrane Nullin Divecha, University of Southampton, UK Phosphoinositides and Nuclear Signaling Tamas Balla, NICHD, National Institutes of Health, USA Phosphatidylinositol 4-Kinases: Keys to Lipid Transport and Metabolism Miguel Murillo, Institute of Cancer Research, UK Short Talk: Disrupting RAS-PI3K Interaction Promotes EFGR-Induced Tumor Regression Abrogating RAC1-Mediated Positive Feedback Loop Sreenivasa R. Chinni, Wayne State University, USA Short Talk: PI4KIII Alpha-CXCR4 Axis Cross-Talk in Prostate Cancer Promotes Cell Invasion Panel: Career Development Brooke M. Emerling, Sanford Burnham Prebys Medical Discovery Institute, USA Igor Vivanco, Institute of Cancer Research, UK Sue Menon, Novartis, USA Pamela L. Schwartzberg, NHGRI, National Institutes of Health, USA Overgrowth Syndromes *Edith M. Hessel, GlaxoSmithKline, UK Robert K. Semple, University of Cambridge, UK Human Disorders of Growth due to Type 1A PI3K Mutations Kathleen Millen, Seattle Children's Research Institute, USA The Role of PIK3CA in Megalencephaly and Epilepsy Cameron C. Trenor III, Boston Children's Hospital, USA Overgrowth and Vascular Anomalies: PIK3CA Heterogeneity and Sirolimus Responses Ghayda Mirzaa, Seattle Children's Hospital, USA Short Talk: Mosaic and Constitutional Mutations of the PI3K-AKT-MTOR Pathway are Associated with a Wide Spectrum of Developmental Brain Disorders from Focal Cortical Dysplasia to Diffuse Megalencephaly with Autism Poster Session 3 MONDAY, JANUARY 23 PI3K in Immunity and Infection *David A. Fruman, University of California, Irvine, USA Klaus Okkenhaug, Babraham Institute, UK Class I PI3K Isoforms and Mutants in Immunity, Infection and Cancer Pamela L. Schwartzberg, NHGRI, National Institutes of Health, USA PIK3CD and Immunodeficiency Laurence A. Turka, Massachusetts General Hospital, USA PI3K Signaling and Metabolism in Regulatory T Cells Edith M. Hessel, GlaxoSmithKline, UK Developing PI3K Inhibitors for COPD and Respiratory Disease Christoph Burkhart, Novartis Institutes for BioMedical Research, Switzerland Short Talk: The PI3K-Delta Inhibitor CDZ173 (leniolisib) Rescues the Immune Cell Defects and Improves the Clinical Course in Patients with Activated PI3K-delta Syndrome (APDS) Carrie L. Lucas, Yale University, USA Short Talk: Human Immune Dysregulation Caused by Mutations in the Gene Encoding the p110g PI3K Subunit Workshop 2: PI3K in Immune Disorders and Immuno-Oncology *Carrie L. Lucas, Yale University, USA *Christoph Burkhart, Novartis Institutes for BioMedical Research, Switzerland Honyin Chiu, University of California, Irvine, USA A Novel Role for the 4E-BP/eIF4E Axis in B Cell Antibody Class Switching Elissa K. Deenick, Garvan Institute of Medical Research, Australia Over Activation of PI3K Causes Defects In B-Cell Development and Differentiation Anne-Katrien Stark, Babraham Institute, UK PI3Kdelta Hyper-Activation Results in Increased Susceptibility to S. Pneumoniae Airway Infection Maria Gonzalez-Nunez, Queen Mary University of London, UK The Role of p110delta PI3K Signaling in NOD2-Mediated Gastrointestinal Immunity and Inflammation Aimé Cézaire Adiko, Center for Research on Inflammation/ Paris University, France Opposite Effects of two PI3K Gamma Regulatory Subunits in Dendritic Cells Anita Chandra, Babraham Institute, UK B Cell Function and Development in the Context of PI3Kdelta Hyper-Activation Sarah H. Ross, University of Dundee, Scotland Understanding the Regulation of PI(3,4,5)P3 Levels in Effector Cytotoxic T Lymphocytes PI3K and Oncology *John Blenis, Weill Cornell Medical College, USA Mika Derynck, Genentech, Inc., USA Clinical Drug Development of PI3K Pathway Inhibitors in Solid Tumors: Threading the Needle for a Therapeutic Index Sabina C. Cosulich, AstraZeneca, UK Clinical Development of mtor Inhibitors Jennifer R. Brown, Dana-Farber Cancer Institute, USA Clinical Development of PI3K Inhibitors for CLL Closing Keynote Address Lewis C. Cantley, Weill Cornell Medicine, USA PI3K and Cancer Metabolism Meeting Wrap-Up: Outcomes and Future Directions (Organizers)

5 TUESDAY, JANUARY 24 Departure