Program Director/Principal Investigator (Last, First, Middle): Hines, O.J BIOGRAPHICAL SKETCH Provide the following information for the Senior/key personnel and other significant contributors in the order listed on Form Page Follow this format for each person DO NOT EXCEED FOUR PAGES NAME POSITION TITLE Miller, Laurence J Professor of Medicine Professor of Biochemistry/Molecular Biology eRA COMMONS USER NAME (credential, e.g., agency login) LJMMCA EDUCATION/TRAINING (Begin with baccalaureate or other initial professional education, such as nursing, include postdoctoral training and residency training if applicable.) DEGREE INSTITUTION AND LOCATION MM/YY FIELD OF STUDY (if applicable) Pennsylvania State Univ., State College, PA Jefferson Medical College, Philadelphia, PA University of Minnesota, St Paul, MN Yale Univ School of Medicine, New Haven, CT B.S M.D M.S Postdoctoral 09/71 07/73 07/78 12/80 Pre-Med Medicine Medicine Cell Biology A Personal Statement The major goal of this grant is to facilitate and promote research in pancreatic cancer Dr Miller’s role is on the External Advisory Board B Positions and Honors Positions and Employment 1973-1974 1974-1976 1976-1979 1979-1982 1982-1985; 1985-1990; 1990-present 1988-1995; 1995-present 1995-present 2002-2010 2010-present Intern, Internal Medicine, Thomas Jefferson University Hospital Resident, Internal Medicine, Mayo Graduate School of Medicine NIH Trainee, Gastroenterology, Mayo Graduate School of Medicine Post-doctoral Fellow, Cell Biology, Yale Univ School of Medicine Assist., Assoc., and Prof of Med., Mayo Clinic College of Medicine Assoc and Prof of Biochem./Mol Biol., Mayo Clinic Graduate School Joint appointment, Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic Graduate School Dir of Research, Mayo Clinic AZ; Assoc Dean of Res., Mayo Clinic Dir HEALTH Program, joint Mayo-ASU program on obesity, diabetes, and vascular disease Other Experience and Professional Memberships 1989-present Member, American Society for Clinical Investigation 1991-1996 Associate Editor, Gastroenterology 1993; 1994; 1995-1999; 2007-2011 Ad hoc and Member, NIH GMA-2, GCMB, and CIMG Study Sections 1995-1999 Chair, Pancreatic Interest Group and Member of Council, AGA 1996-present Member, Association of American Physicians 1997-2001 Editorial Board, American Journal of Physiology 1999-2004; 2002-2003 Councilor and President, American Pancreatic Association 2002-present Editorial Board, Molecular Pharmacology 2010-present Editorial Board, Journal of Biological Chemistry Honors 2000 2001-2011 2002-present PHS 398/2590 (Rev 06/09) Research Career Achievement Award, Department of Medicine, Mayo Clinic MERIT Award, NIDDK Karl F & Marjory Hasselman Professor of Research, Mayo Clinic endowed chair Page _ Biographical Sketch Format Page Program Director/Principal Investigator (Last, First, Middle): 2008-present Hines, O.J Distinguished Mayo Clinic Investigator Award C Selected Peer-reviewed Publications (selected from 355 peer-reviewed publications) Most relevant to the current application: Cheng ZJ, Harikumar KG, Ding WQ, Holicky EL, Miller LJ Analysis of the cellular and molecular mechanisms of trophic action of a misspliced form of the type B cholecystokinin receptor present in colon and pancreatic cancer Cancer Letters 222:95-105, 2005 Korner M, Hayes GM, Rehmann R, Zimmermann A, Buchler MW, Friess H, Miller LJ, Reubi JC Secretin receptors in normal and diseased human pancreas: marked reduction of receptor binding in ductal neoplasia Amer J Pathol 167:959-968, 2005 Hayes GM, Carrigan PE, Beck AM, Miller LJ Targeting the RNA splicing machinery as a novel treatment strategy for pancreatic carcinoma Canc Res 66:3819-3827, 2006 Korner M, Hayes GM, Rehmann R, Zimmermann A, Scholz A, Wiedenmann B, Miller LJ, Reubi JC Secretin receptors in the human liver: expression in biliary tract and cholangiocarcinoma, but not in hepatocytes or hepatocellular carcinoma J Hepatol 45:825-835, 2006 Hayes GM, Carrigan PE, Miller LJ Serine-Arginine Protein Kinase overexpression is associated with tumorigenic imbalance in mitogen-activated protein kinase pathways in breast, colonic, and pancreatic carcinomas Cancer Res 67:2072-2080, 2007 Carrigan PE, Hentz JG, Gordon G, Morgan JL, Raimondo M, Anbar AD, Miller LJ Distinctive heavy metal composition of pancreatic juice in patients with pancreatic carcinoma Canc Epidemiol Biomarker Prevention 16:2656-2663, 2007 Korner M, Hayes GM, Carrigan P, Rehmann R, Miller LJ, Reubi JC Wild-type and splice variant secretin receptors in human lung cancer: overexpression in carcinoid tumors and peritumoral lung tissue Modern Pathol 21:387-395, 2008 Korner M, Waser B, Reubi JC, Miller LJ CCK2 receptor splice variant with intron retention in human gastrointestinal and lung tumors J Cell Mol Med 14:933-943, 2010 PMCID: PMC2888751 Carrigan PE, Bingham JL, Srinivasan S, Brentnall TA, Miller LJ Characterization of alternative spliceoforms and RNA splicing machinery in pancreatic cancer Pancreas 40:281-288, 2011 PMCID: PMC3038180 10 Katchman BA, Antwi K, Hostetter G, Demeure MJ, Watanabe A, Decker GA, Miller LJ, Von Hoff DD, Lake DF Quiescin sulfhydryl oxidase promotes invasion of pancreatic tumor cells mediated by matrix metalloproteinases Molec Cancer Res 9:1621-1631, 2011 PMID: 2198104 PMCID N/A D Research Support Ongoing Research Support R01 DK032878 Miller (PI) 08/01/2006 – 07/31/2015 The long-term goal of this grant (now in years 30-34) is to understand the role of the CCK receptor in health and disease, with the component aims of this cycle directed toward the molecular basis for binding small molecule ligands to the allosteric pocket and the impact of the lipid bilayer on receptor structure and function, as well as the ability to take advantage of this in CCK receptor-active drug development PHS 398/2590 (Rev 06/09) Page _ Biographical Sketch Format Page Program Director/Principal Investigator (Last, First, Middle): Hines, O.J Role: PI R01 DK046577 Miller (PI) 02/01/2010 – 01/31/2014 Secretin Receptor Structure, Function, and Regulation The long-term goal of this grant (now in years 16-19) is to understand the role of the secretin receptor in health and disease There are component parts directed toward understanding the global structure of the receptor, the molecular basis of G protein coupling, and characteristics of druggable pockets within this receptor Role: PI P50 CA102701 Petersen (PI) 09/01/2008 – 08/31/2013 Mayo Clinic SPORE in Pancreatic Cancer The major goal is to facilitate and promote research in pancreatic cancer With a paucity of research in pancreatic cancer, the main emphasis is on the discovery of novel mechanisms and pathways that contribute to the pathogenesis of pancreatic carcinoma, which in turn can translate into strategies for prevention, early detection, and treatment Dr Miller’s role is on the Executive Committee and in the Administrative Core Role: Co-Investigator PHS 398/2590 (Rev 06/09) Page _ Biographical Sketch Format Page