Scientific Organizers: Leon O. Murphy, Novartis Pharmaceuticals, USA Klaus Okkenhaug, Babraham Institute, UKSabina C. Cosulich, AstraZeneca, UKThe 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

www.keystonesymposia.org/meetings | 1.800.253.0685 | 1.970.262.1230

a 501(c)(3) nonprofit educational organization

January 19–23, 2017 | Hilton Santa Fe Historic Plaza Hotel | Santa Fe, New Mexico | USA

PI3K Pathways in Immunology, Growth Disorders and Cancer

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 www.keystonesymposia.org/17A6

THURSDAY, JANUARY 19Arrival and Registration

FRIDAY, JANUARY 20PI3K Function and Physiology *Lewis C. Cantley, Weill Cornell Medicine, USA*Doreen A. Cantrell, University of Dundee, UKLen R. Stephens, Babraham Institute, UKSignaling via Class I PI3KsBart Vanhaesebroeck, University College London, Cancer Institute,UKPhysiological Roles of PI3K IsoformsMatthias P. Wymann, University of Basel, SwitzerlandComplexity in PI3K Signaling and Targeting Jeffrey L. Kutok, Infinity Pharmaceuticals, USAThe PI3K-gamma Inhibitor, IPI-549, Increases Antitumor Immunity byTargeting Tumor-Associated Myeloid Cells and Overcomes ImmuneCheckpoint Blockade Resistance in Preclinical Tumor ModelsJohn E. Burke, University of Victoria, CanadaShort Talk: Conformational Disturbance of PI3Kdelta Regulation byPrimary Immunodeficiency Mutations in PIK3CD and PIK3R1Kyle A. Edgar, Genentech, Inc., USAShort Talk: The PI3K Inhibitor, Taselisib, has Enhanced Potency inPIK3CA Mutant Models Through a Unique Mechanism of Action

PI3K Effectors *Sabina C. Cosulich, AstraZeneca, UK*Igor Vivanco, Institute of Cancer Research, UKBrendan D. Manning, Harvard School of Public Health, USAThe TSC-Rheb-mTOR Circuit and Metabolic ControlDavid A. Fruman, University of California, Irvine, USAThe mTORC1/4E-BP/eIF4E Axis in B-Cell Activation andTransformationJohn Blenis, Weill Cornell Medical College, USAmTORC1/S6K1: Regulation of RNA Biogenesis, Protein Synthesisand Cell MetabolismIvan Yudushkin, Medical University of Vienna, AustriaShort Talk: Membrane Subpopulations of mTORC2 Display DistinctSensitivity to PI3K

Poster Session 1

SATURDAY, JANUARY 21Phosphatases *Len R. Stephens, Babraham Institute, UK*Brendan D. Manning, Harvard School of Public Health, USARamon Parsons, Icahn School of Medicine at Mount Sinai, USAPTEN Upstream, Instream and DownstreamLloyd Trotman, Cold Spring Harbor Laboratory, USAPTEN Function and Loss of Function in Prostate MetastasisChristina Anne Mitchell, Monash University, AustraliaNew Roles for Inositol Polyphosphate PhosphatasesDoreen A. Cantrell, University of Dundee, UKPhosphatidylinositol-3-Kinase Control of T Lymphocyte Differentiation:Dogma Versus Reality

Ana Clara Carrera, Centro Nacional Biotechnologia/CSIC, SpainShort Talk: PI3K Depletion Induces Tumor Regression; E-CadherinDownregulation Sensitizes PTEN-Mutant Tumors to PI3K-BetaSilencingSarah Elizabeth Conduit, Monash University, AustraliaShort 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, CanadaJack Flanagan, University of Auckland, New ZealandEvidence of a New Mechanism for Achieving PI3K Inhibition withSmall Molecules via an Effect on Membrane BindingThomas Leonard, Max F. Perutz Laboratories GmbH, AustriaPI(3,4,5)P3 Allosterically Activates AktErika Ilagan, Harvard T.H. Chan School of Public Health, USAThe TSC-Rheb-mTORC1 Circuit is a Shared Effector of PI3K-Akt andRas-Erk SignalingGina Lee, Weill Cornell Medicine, USAmTORC1-S6K1 Regulation of SR Protein Kinase Links mRNABiogenesis to De Novo Lipid SynthesisMarie H. Solheim, Joslin Diabetes Center, Harvard Medical School,USAConserved p85alpha SH2 Domain Residues Play Differential Roles inp85alpha-IRS-1 BindingLukasz Pawel Magiera, University of Cambridge, UKPik3ca Gain-of-Function Mutation Restricted to Mesenchymal CellsExpressing Fibroblast Activation Protein-Alpha Causes SkeletalOvergrowth

Class II/III PI3Ks *Jonathan M. Backer, Albert Einstein College of Medicine, USAVolker Haucke, Leibniz Institut für Molekulare Pharmakologie,GermanyPhosphoinositide Conversion in the Endolysosomal SystemLeon O. Murphy, Novartis Pharmaceuticals, USAVPS34 Inhibitors and Autophagy Emilio Hirsch, Fondazione per la Ricerca Biomedica – ONLUS, ItalyClass II PI3K in MitosisRuzica Bago, University of Dundee, UKShort Talk: The hVps34-SGK3 Pathway Alleviates Sustained PI3K/AktInhibition by Stimulating mTORC1 and Tumour Growth

Poster Session 2

SUNDAY, JANUARY 22Signaling from Non-Canonical PI Kinases *Bart Vanhaesebroeck, University College London, Cancer Institute,UK*Klaus Okkenhaug, Babraham Institute, UKBrooke M. Emerling, Sanford Burnham Prebys Medical DiscoveryInstitute, USAPI5P4Ks and Cancer Metabolism

* Session Chair † Invited but not yet accepted Program current as of January 7, 2017. Program subject to change. Meal formats are based on meeting venue.For the most up-to-date details, visit www.keystonesymposia.org/17A6.

KEYSTONE SYMPOSIAon Molecular and Cellular Biology

PI3K Pathways in Immunology, Growth Disorders and Cancer (A6)January 19-23, 2017 • Hilton Santa Fe Historic Plaza Hotel • Santa Fe, New Mexico, USA

Scientific Organizers: Leon O. Murphy, Klaus Okkenhaug and Sabina C. CosulichSponsored by Bayer HealthCare Pharmaceuticals, Cell Signaling Technology, Inc., Incyte Corporation and Pfizer Inc.

Abstract & Scholarship Deadline: September 21, 2016 / Abstract Deadline: October 19, 2016 / Discounted Registration Deadline: November 16, 2016

* Session Chair † Invited but not yet accepted Program current as of January 7, 2017. Program subject to change. Meal formats are based on meeting venue.For the most up-to-date details, visit www.keystonesymposia.org/17A6.

KEYSTONE SYMPOSIAon Molecular and Cellular Biology

PI3K Pathways in Immunology, Growth Disorders and Cancer (A6)January 19-23, 2017 • Hilton Santa Fe Historic Plaza Hotel • Santa Fe, New Mexico, USA

Scientific Organizers: Leon O. Murphy, Klaus Okkenhaug and Sabina C. CosulichSponsored by Bayer HealthCare Pharmaceuticals, Cell Signaling Technology, Inc., Incyte Corporation and Pfizer Inc.

Abstract & Scholarship Deadline: September 21, 2016 / Abstract Deadline: October 19, 2016 / Discounted Registration Deadline: November 16, 2016

Pietro V. De Camilli, Yale University School of Medicine, USAPhosphoinositide Dynamics at the Plasma MembraneNullin Divecha, University of Southampton, UKPhosphoinositides and Nuclear SignalingTamas Balla, NICHD, National Institutes of Health, USAPhosphatidylinositol 4-Kinases: Keys to Lipid Transport andMetabolismWei-Xing Zong, Rutgers University, USAShort Talk: PI3-Kinase p110beta Regulates Cell Metabolism andOncogenesis by Promoting Endocytic Turnover of Nutrient TransportersSreenivasa R. Chinni, Wayne State University, USAShort Talk: PI4KIII Alpha-CXCR4 Axis Cross-Talk in Prostate CancerPromotes Cell Invasion

Panel: Career Development *Leon O. Murphy, Novartis Pharmaceuticals, USABrooke M. Emerling, Sanford Burnham Prebys Medical DiscoveryInstitute, USAIgor Vivanco, Institute of Cancer Research, UKSue Menon, Novartis, USAPamela L. Schwartzberg, NHGRI, National Institutes of Health, USA

Overgrowth Syndromes *Edith M. Hessel, GlaxoSmithKline, UK*Leon O. Murphy, Novartis Pharmaceuticals, USARobert K. Semple, University of Cambridge, UKHuman Disorders of Growth due to Type 1A PI3K MutationsKathleen Millen, Seattle Children's Research Institute, USAThe Role of PIK3CA in Megalencephaly and EpilepsyCameron C. Trenor III, Boston Children's Hospital, USAOvergrowth and Vascular Anomalies: PIK3CA Heterogeneity andSirolimus ResponsesGhayda Mirzaa, Seattle Children's Hospital, USAShort Talk: Mosaic and Constitutional Mutations of thePI3K-AKT-MTOR Pathway are Associated with a Wide Spectrum ofDevelopmental Brain Disorders from Focal Cortical Dysplasia toDiffuse Megalencephaly with Autism

Poster Session 3

MONDAY, JANUARY 23PI3K in Immunity and Infection *David A. Fruman, University of California, Irvine, USAKlaus Okkenhaug, Babraham Institute, UKClass I PI3K Isoforms and Mutants in Immunity, Infection and CancerPamela L. Schwartzberg, NHGRI, National Institutes of Health, USAPIK3CD and ImmunodeficiencyLaurence A. Turka, Massachusetts General Hospital, USAPI3K Signaling and Metabolism in Regulatory T CellsEdith M. Hessel, GlaxoSmithKline, UKDeveloping PI3K Inhibitors for COPD and Respiratory Disease

Christoph Burkhart, Novartis Institutes for BioMedical Research,SwitzerlandShort Talk: The PI3K-Delta Inhibitor CDZ173 (leniolisib) Rescues theImmune Cell Defects and Improves the Clinical Course in Patientswith Activated PI3K-delta Syndrome (APDS)Carrie L. Lucas, Yale University, USAShort Talk: Human Immune Dysregulation Caused by Mutations in theGene 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,SwitzerlandHonyin Chiu, University of California, Irvine, USAA Novel Role for the 4E-BP/eIF4E Axis in B Cell Antibody ClassSwitchingElissa K. Deenick, Garvan Institute of Medical Research, AustraliaOver Activation Of PI3K Causes Defects In B-Cell Development andDifferentiationAnne-Katrien Stark, Babraham Institute, UKPI3Kdelta Hyper-Activation Results in Increased Susceptibility to S.Pneumoniae Airway InfectionMaria Gonzalez-Nunez, Queen Mary University of London, UKThe Role of p110delta PI3K Signaling in NOD2-MediatedGastrointestinal Immunity and InflammationAimé Cézaire Adiko, Center for Research on Inflammation/ ParisUniversity, FranceOpposite Effects of two PI3K Gamma Regulatory Subunits inDendritic Cells Anita Chandra, Babraham Institute, UKB Cell Function and Development in the Context of PI3KdeltaHyper-Activation Sarah H. Ross, University of Dundee, ScotlandUnderstanding the Regulation of PI(3,4,5)P3 Levels in EffectorCytotoxic T Lymphocytes

PI3K and Oncology *John Blenis, Weill Cornell Medical College, USAMika Derynck, Genentech, Inc., USAClinical Drug Development of PI3K Pathway Inhibitors in SolidTumors: Threading the Needle for a Therapeutic IndexSabina C. Cosulich, AstraZeneca, UKClinical Development of mTOR InhibitorsJennifer R. Brown, Dana-Farber Cancer Institute, USAClinical Development of PI3K Inhibitors for CLL

Closing Keynote Address *Leon O. Murphy, Novartis Pharmaceuticals, USALewis C. Cantley, Weill Cornell Medicine, USAPI3K and Cancer Metabolism

Meeting Wrap-Up: Outcomes and Future Directions (Organizers)

* Session Chair † Invited but not yet accepted Program current as of January 7, 2017. Program subject to change. Meal formats are based on meeting venue.For the most up-to-date details, visit www.keystonesymposia.org/17A6.

KEYSTONE SYMPOSIAon Molecular and Cellular Biology

PI3K Pathways in Immunology, Growth Disorders and Cancer (A6)January 19-23, 2017 • Hilton Santa Fe Historic Plaza Hotel • Santa Fe, New Mexico, USA

Scientific Organizers: Leon O. Murphy, Klaus Okkenhaug and Sabina C. CosulichSponsored by Bayer HealthCare Pharmaceuticals, Cell Signaling Technology, Inc., Incyte Corporation and Pfizer Inc.

Abstract & Scholarship Deadline: September 21, 2016 / Abstract Deadline: October 19, 2016 / Discounted Registration Deadline: November 16, 2016

TUESDAY, JANUARY 24Departure

* Session Chair † Invited but not yet accepted Program current as of January 7, 2017. Program subject to change. Meal formats are based on meeting venue.For the most up-to-date details, visit www.keystonesymposia.org/17A6.

KEYSTONE SYMPOSIAon Molecular and Cellular Biology

PI3K Pathways in Immunology, Growth Disorders and Cancer (A6)January 19-23, 2017 • Hilton Santa Fe Historic Plaza Hotel • Santa Fe, New Mexico, USA

Scientific Organizers: Leon O. Murphy, Klaus Okkenhaug and Sabina C. CosulichSponsored by Bayer HealthCare Pharmaceuticals, Cell Signaling Technology, Inc., Incyte Corporation and Pfizer Inc.

Abstract & Scholarship Deadline: September 21, 2016 / Abstract Deadline: October 19, 2016 / Discounted Registration Deadline: November 16, 2016