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Cravatt, Benjamin F. BENJAMIN F. CRAVATT, III PROFESSOR The Department Chemical Physiology and Skaggs Institute for Chemical Biology The Scripps Research Institute 10550 N. Torrey Pines Road, BCC-157 La Jolla, CA 92037 (858)-784-8633 Email: [email protected] Biographical Data Born: April 13, 1970; Houston, TX Education 1992 B.S., Stanford University, Biological Sciences (with Honors) B.A., Stanford University, History 1996 Ph.D., The Scripps Research Institute, Macromolecular and Cellular Structure and Chemistry, 1996 Scientific Positions 1996-2001 Assistant Professor, The Skaggs Institute for Chemical Biology and Department of Cell Biology, The Scripps Research Institute (TSRI) 2000-2001 Assistant Professor, Department of Chemistry, TSRI 2001-2004 Associate Professor (with tenure), Departments of Cell Biology and Chemistry, TSRI 2002-present Director, Helen L. Dorris Child and Adolescent Neuro-Psychiatric Disorder Institute 2004-present Norton B. Gilula Chair in Chemical Biology, TSRI 2004 – 2007 Professor, Departments of Cell Biology and Chemistry, TSRI 2007-present Professor and Chair, Department of Chemical Physiology, TSRI 1 Cravatt, Benjamin F. Awards 1992 Phi Beta Kappa, Stanford University 1992 The Block “S” Honors Award, Stanford University Athletics 1992-1995 NSF Predoctoral Fellow 1997 Fumio Mekata Fellow, Woods Hole Marine Biological Laboratory, Summer Neurobiology Course 1997-1998 Baxter Foundation Fellow 1998-2001 Searle Scholar 2002 Technology Review’s TR100 Top 100 Young Innovators Award 2002 Promega Award for Early Career Life Scientists, American Society for Cell Biology 2004 Eli Lilly Award in Biological Chemistry, American Chemical Society 2005 Cope Scholar Award, American Chemical Society 2005 Young Investigator Award, International Cannabinoid Research Society 2007 Young Investigator Award, Linda and Jack Gill Center for Biomolecular Science, Indiana University 2007 Irving Sigal Young Investigator Award, The Protein Society 2007 Fellow, American Association for the Advancement of Science 2008 Tetrahedron Young Investigator Award in Bioorganic and Medicinal Chemistry, Elsevier 2009 MERIT Award, National Cancer Institute 2009-10 Pfizer Fellowship for Creativity in Chemistry and Chemical Biology Special Lectureships 2002 Eli Lilly Award Symposium in honor of Kevan Shokat, ACS Meeting, Boston, MA 2 Cravatt, Benjamin F. 2003 Alfred Bader Symposium in honor of Christopher Walsh, ACS Meeting, New Orleans, LA 2004 Eli Lilly Lecture, Department of Chemistry, Yale University; Organic Synthesis Inc. Lecture, Carleton College; Keynote Speaker, Volcano Conference in Bioorganic Chemistry, Pack Forest, University of Washington 2005 Novartis Lecture in Organic Chemistry, Department of Chemistry, MIT; Keynote Speaker, Industry University Cooperative Chemistry Program, Texas A&M University 2006 Plenary Lecturer, ABRF Annual Meeting, Long Beach, CA; Keynote Speaker, Canadian Proteomics Initiative International Conference; Troisieme Cycle Lecture Series, Universities of Western Switzerland; Wyeth/Columbia Lecture, Department of Chemistry, Columbia University; State-of-the-Art Lecture, HUPO 2006, Long Beach, CA; Lecturer, Eli Lilly Award Symposium in honor of Linda Hsieh-Wilson, ACS Meeting, San Francisco, CA 2007 Plenary Lecture, Bürgenstock Conference, Bürgenstock Switzerland; Keynote Speaker, 27th Annual Graduate Student Symposium in the Pharmacological Sciences, University of Michigan; Plenary Lecture, 2007 International Conference on Bioactive Lipids in Cancer, Inflammation and Related Diseases, Montreal, Canada; Barnett Lecture, The Barnett Institute and Chemistry Department, Northeastern University; “Cell Biology in Ten Years” Symposium, American Society of Cell Biology Annual Meeting, Washington, D.C. 2008 Lecturer, Nobel Conference on Systems Biology and Child Health, Stockholm, Sweden; Plenary Lecture, British Society for Proteomics Research Annual Meeting, Cambridge, UK; Lecturer, Eli Lilly Award Symposium in honor of Paul Hergenrother, ACS Meeting, Philadelphia, PA; Keynote Speaker, Moores Cancer Center Faculty Retreat, UC San Diego 2009 Keynote Address, Phosphorylation, Signaling & Disease Meeting, CSHL, NY; Lecturer, Johnson Symposium, Chemistry Department, Stanford University; Plenary Lecture, Chemical Biology for Drug Discovery Conference, Oxford, UK 2010 Frontiers in Chemistry Lecture Series, Texas A&M Univeristy; Dauben Lecture, Chemistry Department, University of Washington 3 Cravatt, Benjamin F. Membership, Professional Experience, and Service 1997-present Member, American Chemical Society 2000 Co-Founder, Activx Biosciences (www.activx.com) 2000-present Member, Scientific Advisory Board, Activx Biosciences 2001 Adhoc Member, Bio-organic and Natural Products (BNP) Study Section, NIH 2001, 2002 Adhoc Member, Technologies for Comprehensive, Sensitive and Quantitative Protein Analysis in Human Tumors: Phased Innovation Study Section, NIH 2001-present Member, International Cannabinoid Research Society 2001-present Contributor, Faculty of 1000, Macromolecular Chemistry of the Cell section 2001-2005 Member, Editorial Board, Molecular and Cellular Proteomics 2002, 2003 Adhoc Member, Molecular, Cellular and Developmental Neurosciences Study Section, Special Emphasis Panel, NIH 2002, 2003 Co-Editor (with Ruedi Aebersold), Trends in Proteomics 2002-present Member, Editorial Board, Bioorganic Chemistry 2002-present Member, Scientific Advisory Board, 5AM Ventures 2003 Adhoc Member, Biophysical Chemistry Study Section, NIH 2003-present Member, Society for Neuroscience 2003-present Director, TSRI Graduate Course in Neuroscience 2003-present Consultant, Pfizer Global Research and Development 2003-present Council Member, American Human Proteome Organization (HUPO) 2004-present Member, Editorial Board, Bioorganic Medicinal Chemistry & Bioorganic Medicinal Chemistry Letters 2004-present Member, Editorial Board, Chemistry and Biology 4 Cravatt, Benjamin F. 2004-present Member, Editorial Board, ChemBioChem 2004-present Member, Editorial Board, Molecular Biosystems 2005-present Member, Editorial Advisory Board, Biochemistry 2005-present Member, Editorial Board, Curr. Opin. Chem. Biol. 2005-present Member, Editorial Board, ChemMedChem 2005-present Member, Scientific Advisory Committee, Damon Runyon Cancer Research Foundation 2005-present Member, Educational Advisory Board for Rimonabant, Sanofi-Aventis 2005 Adhoc Member, Synthetic and Biological Chemistry A, Study Section, NIH 2006-present Member, Editorial Board, ACS Chemical Biology 2006 Adhoc Member, Innovative Technologies for the Molecular Analysis of Cancer, Study Section, NIH 2006 Co-Organizer (with Art Horwich) of the 20th Annual Symposium of the Protein Society, San Diego, CA 2007 Co-Organizer (with Michael Rosen) of the ASBMB Annual Meeting, Washington D.C. 2007-present Member, Scientific Advisory Board, Searle Scholars Program 2007-2009 Member, Scientific Advisory Board, Caring for Carcinoid Foundation 2007-present Member, Scientific Advisory Board, aTyr Pharma 2007-present Member, Synthetic and Biological Chemistry A, Study Section, NIH 2008-present Member, TASAP Board, Pfizer Global Research and Development 2009-present Council Member, ASBMB 5 Cravatt, Benjamin F. Publications 1994 Cravatt, B.F., Ashley, J.A., Janda, K.D., Boger, D.L., Lerner, R.A. “Crossing Extreme Mechanistic Barriers By Antibody Catalysis: Syn Elimination to a Cis Olefin”, J. Am. Chem. Soc. 1994, 116, 6013-6014. Boger, D.L., Lerner, R.A., Cravatt, B.F. “Synthesis of a Functionalized Rigid Bicyclo[2.2.1]heptane: A Useful Hapten for Eliciting Catalytic Antibodies”, J. Org. Chem. 1994, 59, 5078-5079. Lerner, R.A., Siuzdak, G., Prospero-Garcia, O., Henriksen, S.J., Boger, D.L., and Cravatt B.F. “Cerebrodiene: A Brain Lipid Isolated from Sleep-Deprived Cats” Proc. Natl. Acad. Sci. U.S.A. 1994, 91, 9505-9508. 1995 Cravatt, B.F., Prospero-Garcia, O., Siuzdak, G., Gilula, N.B., Henriksen, S.J., Boger, D.L., Lerner, R.A. “Chemical Characterization of a Family of Brain Lipids That Induce Sleep” Science 1995, 268, 1506-1509. 1996 Cravatt, B.F., Lerner, R.A., Boger, D.L. “Structure Determination of an Endogenous Sleep- Inducing Lipid, cis-9-Octadecenamide (Oleamide): A Synthetic Approach to the Chemical Analysis of Trace Quantities of a Natural Product” J. Am.Chem. Soc. 1996, 118, 580-509. Patterson, J.E., Ollman, I.R., Cravatt, B.F., Boger D.L. Wong, C.-H., Lerner, R.A. “Inhibition of Oleamide Hydrolase Catalyzed Hydrolysis of the Endogenous Sleep-Inducing Lipid cis-9- Octadecenamide” J. Am. Chem. Soc. 1996, 118, 5938-5945. Cravatt, B.F., Giang, D.K., Mayfield, S.P., Boger, D.L., Lerner, R.A., Gilula, N.B., “Molecular Characterization of an Enzyme that Degrades Neuromodulatory Fatty Acid Amides” Nature 1996, 384, 83-87. 1997 Giang, D.K. & Cravatt, B.F. “Molecular Characterization of Human and Mouse Fatty Acid Amide Hydrolases.” Proc. Natl. Acad. Sci. USA 1997, 94, 2238-2242. Thomas, E.A., Cravatt, B.F., Danielson, P.E., Gilula, N.B., Sutcliffe, J.G. “Fatty Acid Amide Hydrolase (FAAH), the Degradative Enzyme for Anandamide and Oleamide, Has Selective 6 Cravatt, Benjamin F. Distribution in Neurons within the Rat Central Nervous System.” J. Neurosci. Res. 1997, 50, 1047-1052. Arreaza, G., Devane, W.A., Omeir, R.L., Sajnani, G., Kunz, J., Cravatt, B.F., Deutsch, D.G. “The Cloned Rat Hydrolytic Enzyme Responsible for the Breakdown of Anandamide Also Catalyzes its Formation via the Condensation of Arachidonic Acid and Ethanolamine.” Neurosci. Lett. 1997, 234, 59-62. Guan, X., Cravatt, B.F., Ehring, G.R., Hall, J.E., Boger, D.L., Lerner, R.A., Gilula, N.B. “The Sleep-Inducing Lipid Oleamide Deconvolutes Gap Junction Communication and Calcium Wave Transmission in Glial Cells.” J. Cell Biol. 1997, 139, 1785-1792. 1998 Patricelli, M.P., Patterson, J.P., Boger, D.L., Cravatt, B.F. “An Endogenous Sleep Inducing Compound is a Novel Competitive Inhibitor of Fatty Acid Amide Hydrolase (FAAH).” Bioorg. Med. Chem. Lett. 1998, 8, 613-618. Giang, D.K. & Cravatt, B.F. “A Second Mammalian N-Myristoyltransferase.” J. Biol. Chem. 1998, 273, 6595-6598. Patricelli, M.P., Lashuel, H.A., Giang, D.K., Kelly, J.W., and Cravatt, B.F. “Comparative Characterization of a Wild Type and Transmembrane Domain-Deleted Fatty Acid Amide Hydrolase: Identification of the Transmembrane Domain as a Site for Oligomerization.” Biochemistry 1998, 37, 15177-15187. Egertova, M., Giang, D.K., Cravatt, B.F., and Elphick, M.R. “A New Perspective on Cannabinoid Signalling: Complimentary Localization of Fatty Acid Amide Hydrolase and the CB1 Receptor in Rat Brain.” Proc. R. Soc. Lond. B. 1998, 265, 2081-2085. Boger, D.L, Henriksen, S.J., Cravatt, B.F. “Oleamide: An Endogenous Sleep-Inducing Lipid and Prototypical Member of a New Class of Biological Signaling Molecules.” Curr. Pharm. Des. 1998, 4, 303-314. Wan, M., Cravatt B.F., Huijun, Z.R., Xianyu, Z., Francke, U. “Conserved Chromosomal Location and Genomic Structure of Human and Mouse Fatty Acid Amide Hydrolase (FAAH) Genes and Evaluation of Clasper as a Candidate Neurological Mutation.” Genomics 1998, 54, 408-414. Boger, D.L., Patterson, J.E., Guan, X., Cravatt, B.F., Lerner, R.A., Gilula, N.B. “Chemical Requirements for Inhibition of Gap Junction Communication by the Biologically Active Lipid Oleamide.” Proc. Natl. Acad. Sci. U.S.A. 1998, 95, 4810-4815. 7 Cravatt, Benjamin F. 1999 Patricelli, M.P., Lovato, M.A., Cravatt, B.F. “Chemical and Mutagenic Investigations of Fatty Acid Amide Hydrolase: Evidence for a Family of Serine Hydrolases with Distinct Catalytic Properties.” Biochemistry 1999, 38, 9804-9812. Liu, Y., Patricelli, M.P., Cravatt, B.F. “Activity-Based Protein Profiling: The Serine Hydrolases.” Proc. Natl. Acad. Sci. U.S.A. 1999, 96, 14694-14699. Patricelli, M.P., Cravatt, B.F. “Fatty Acid Amide Hydrolase Competitively Degrades Bioactive Amides and Esters through a Nonconventional Catalytic Mechanism.” Biochemistry (accelerated publication) 1999, 38, 14125-14130. Boger, D.L., Sato, H. Lerner, A.E., Austin, B.J., Patterson, J.E., Patricelli, M.P., Cravatt, B.F. “Trifluoromethyl Ketone Inhibitors of Fatty Acid Amide Hydrolase: A Probe of Structural and Conformational Features Contributing to Inhibition.” Biorg. Med. Chem. Lett. 1999, 9, 265-270. Thomas, E.A., Cravatt, B.F., Sutcliffe, J.G. “The Endogenous Lipid Oleamide Activates Serotonin 5-HT7 Neurons in Mouse Thalamus and Hypothalamus.” J. Neurochem. 1999, 72, 2370-2378. 2000 Patricelli M.P., Cravatt B.F. “Clarifying the Catalytic Roles of Conserved Residues in the Amidase Signature Family.” J Biol Chem. 2000, 275, 19177-19184. Kustedjo K., Bracey M.H., Cravatt B.F. “Torsin A and its Torsion Dystonia-Associated Mutant Form Are Lumenal Glycoproteins that Exhibit Distinct Subcellular Localizations.” J Biol Chem. 2000, 275, 27933-27939. Boger, D.L., Sato, H., Lerner, A.E., Hedrick, M.P., Fecik, R.A., Miyauch,i H., Wilkie, G.D., Austin, B.J., Patricelli, M.P., Cravatt, B.F. “Exceptionally Potent Inhibitors of Fatty Acid Amide Hydrolase: the Enzyme Responsible for Degradation of Endogenous Oleamide and Anandamide.” Proc Natl Acad Sci U S A. 2000, 97, 5044-5049. Cravatt, B.F., Sorensen, E.J. “Chemical Strategies for the Global Analysis of Protein Function.” Curr. Opin. Chem. Biol. 2000, 4, 663-668. Egertova, M., Cravatt B.F., Elphick, M.R. “Fatty Acid Amide Hydrolase Expression in Rat Choroid Plexus: Possible Role in Regulation of the Sleep-Inducing Action of Oleamide.” Neurosci. Lett. 2000, 282, 13-16. Boger, D.L., Fecik, R.A., Patterson, J.E., Miyauchi, H., Patricelli, M.P., Cravatt, B.F. “Fatty Acid Amide Hydrolase Substrate Specificity.” Bioorg. Med. Chem. Lett. 2000, 2613-2616. 8 Cravatt, Benjamin F. Wang, E.W., Kessler, B.M., Borodovsky, A., Cravatt, B.F., Bogyo, M., Ploegh, H.L., Glas, R. “Integration of the Ubiquitin-Proteasome Pathway with a Cytosolic Oligopeptidase Activity.” Proc Natl Acad Sci U S A. 2000, 97, 9990-9995. 2001 Adam, G.C., Cravatt, B.F., Sorensen, E.J. “Profiling the Specific Reactivity of the Proteome with Non-Directed Activity-Based Probes.” Chem. Biol. 2001, 8, 81-95. Kidd, D. Liu, Y., Cravatt B.F. “Profiling Serine Hydrolase Activities in Complex Proteomes.” Biochemistry 2001, 40, 4005-4015. Patricelli, M.P., Cravatt, B.F. “Characterization and Manipulation of the Acyl Chain Selectivity of Fatty Acid Amide Hydrolase.” Biochemistry 2001, 40, 6107-6115. Cravatt, B.F., Demarest, K., Patricelli, M.P., Bracey, M.H., Giang, D.K., Martin, B.R., Lichtman, A.H. “Supersensitivity to Anandamide and Enhanced Endogenous Cannabinoid Signaling in Mice Lacking Fatty Acid Amide Hydrolase.” Proc. Natl. Acad. Sci. U S A. 2001 98, 9371-9376. Patricelli, M.P., Cravatt, B.F. “Proteins Regulating the Biosynthesis and Inactivation of Neuromodulatory Fatty Acid Amides.” Vitam Horm. 2001, 62, 95-131. Huitron-Resendiz, S., Gombart, L., Cravatt, B.F., Henriksen, S.J. “Effect of Oleamide on Sleep and its Relationship to Blood Pressure, Body Temperature, and Locomotor Activity in Rats.” Exp. Neurol. 2001, 172, 235-243. Larsen, N.A., Heine, A., Crane, L., Cravatt, B.F., Lerner, R.A., Wilson, I.A. “Structural Basis for a Disfavored Elimination Reaction in a Catalytic Antibody 1D4.” J. Mol. Biol. 2001, 314, 93- 102. 2002 Lichtman, A.H, Hawkins, E.G., Griffin, G., Cravatt, B.F. “The Pharmacological Activity of Fatty Acid Amides is Regulated, not Mediated by Fatty Acid Amide Hydrolase In Vivo.” J. Pharmacol. Exp. Ther. 2002, 302, 73-79. Sipe, J.C., Chiang, K., Gerber, A., Beutler, E., Cravatt, B.F. “A Missense Mutation in Human Fatty Acid Amide Hydrolase Associated with Problem Drug Use.” Proc. Natl. Acad. Sci. U.S.A. 2002, 99, 8394-8399. Adam, G.C., Sorensen, E.J., Cravatt, B.F. “Proteomic Profiling of Mechanistically Distinct Enzyme Classes Using a Common Chemotype.” Nat. Biotechnol. 2002, 20, 805-809. Jessani, N., Liu, Y., Humphrey, M., Cravatt, B.F. “Enzyme Activity Profiles of the Secreted and Membrane Proteome that Depict Cancer Invasiveness.” Proc. Natl. Acad. Sci. U.S.A. 2002, 99, 10335-10340. 9 Cravatt, Benjamin F. Aebersold, R., Cravatt, B.F. “Proteomics: Advances, Applications, and the Challenges that Remain.” Trends Proteomics 2002, 20, S1-S2. Cravatt, B.F., Lichtman, A.H. “The Enzymatic Inactivation of Fatty Acid Amide Signaling In Vivo.” Chem. Phys. Lipids 2002, 121, 135-48. Adam, G.C., Sorensen, E.J., Cravatt, B.F. “Chemical Strategies for Functional Proteomics.” Mol. Cell. Proteomics 2002, 1, 781-790. Adam, G.C., Sorensen, E.J., Cravatt, B.F. “Trifunctional Chemical Probes for the Consolidated Detection and Identification of Enzyme Activities in Complex Proteomes.” Mol. Cell. Proteomics 2002, 1, 828-835. Bracey, M.H., Hansen, M., Masuda, K., Stevens, R.C., Cravatt, B.F. “Structural Adaptations in a Membrane Enzyme that Terminates Endocannabinoid Signaling.” Science 2002, 298,1793-1796. 2003 Speers, A.E., Adam, G.C., Cravatt, B.F. “Activity-Based Protein Profiling In Vivo Using a Copper(I)-Catalyzed Azide-Alkyne Cycloaddition.” J. Amer. Chem. Soc. 2003, 125, 4686-4687. Clement, A.B., Hawkins, E.G., Lichtman, A.H., Cravatt, B.F. “Increased Seizure Susceptibility and Pro-Convulsant Activity of Anandamide in Mice Lacking Fatty Acid Amide Hydrolase.” J. Neurosci. 2003, 23, 3916-3923. Egertova, M., Cravatt, B.F., Elphick, M.R. “Comparative Analysis of Fatty Acid Amide Hydrolase and CB(1) Cannabinoid Receptor Expression in the Mouse Brain: Evidence of a Widespread Role for Fatty Acid Amide Hydrolase in Regulation of Endocannabinoid Signaling.” Neuroscience 2003, 119, 481-496. Leung, D., Hardouin, C., Boger, D.L., Cravatt, B.F. “Discovering Potent and Selective Reversible Inhibitors of Enzymes in Complex Proteomes.” Nat. Biotechnol. 2003, 21, 687-691. McKinney, M.K., Cravatt, B.F. “Evidence for Distinct Roles in Catalysis for Residues of the Serine-Serine-Lysine Catalytic Triad of Fatty Acid Amide Hydrolase.” J. Biol. Chem. 2003, 278, 37393-37399. Liu, J., Batkai, S., Pacher, P., Harvey-White, J., Wagner, J.A., Cravatt, B.F., Gao, B., and Kunos, G.“LPS Induces Anandamide Synthesis in Macrophages via CD14/MAPK/PI3K/NF-kappaB Independently of Platelet Activating Factor.” J. Biol. Chem. 2003, 278, 45034-45039. Adam, G.C., Vanderwal, C.D., Sorensen, E.J., Cravatt, B.F. “The Natural Product FR182877 is a Potent and Selective Inhibitor of Carboxylesterase-1.” Angew. Chem. Int. Ed. 2003, 42, 5480- 5484. 10

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Novartis Lecture in Organic Chemistry, Department of Chemistry, MIT; striatal cannabinoid CB1 receptor function correlates with the antianxiety effects of fatty
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Most books are stored in the elastic cloud where traffic is expensive. For this reason, we have a limit on daily download.