Program Director/Principal Investigator (Last, First, Middle): Parra, Karlett J. BIOGRAPHICAL SKETCH NAME POSITION TITLE Karlett J. Parra, Ph.D. Associate Professor P30 Role: Full Member Translational Cancer Biology & Signaling eRA COMMONS USER NAME (credential, e.g., agency login) KJParra 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) Universidad Simon Bolivar, Caracas,Venezuela Universidad Simon Bolivar, Caracas,Venezuela SUNY Upstate Medical University, Syracuse, NY B.S. M.S. Ph.D. May 1990 July 1992 May 1998 Biology Biochemistry Biochemistry & Mol. Biol. A. Personal Statement Our lab studies the molecular mechanisms that regulate function and assembly of V-ATPase proton pumps. We study he fundamental processes by which V-ATPase assists cells in sustaining pH and energy homeostasis in yeast (S. cerevisiae). In pathogenic fungi (C. albicans), we investigate the contributions of VATPases to filamentation and virulence. In prostate and breast cancer we study the mechanisms by which VATPases regulate androgen receptor and estrogen receptor functions and as well as V-ATPase contributions to cell survival and metastasis. B. Positions And Honors Positions & Employment Dec. 1997 - Aug.1999 Aug. 1999 - June 2000 Aug. 2000 - Aug. 2004 Aug. 2004 - Dec. 2006 Jan. 2007 - July 2010 July 2010 - present July 2012 - present Post-Doctoral Research Associate. Dr. Patricia M. Kane, Dept. of Biochemistry and Molecular Biology, SUNY Upstate Medical University, Syracuse, NY. Visiting Assistant Professor. Dept. of Biology, Le Moyne College, Syracuse, NY. Assistant Professor. Dept. of Chemistry, Ball State University, Muncie, IN. Associate Professor. Dept. of Chemistry, Ball State University, Muncie, IN. Assistant Professor. Dept. of Biochemistry and Molecular Biology, School of Medicine, University of New Mexico, Albuquerque, NM. Associate Professor. Dept. of Biochemistry and Molecular Biology, School of Medicine, University of New Mexico, Albuquerque, NM. Chair, Dept. of Biochemistry and Molecular Biology, School of Medicine, University of New Mexico, Albuquerque, NM. Leadership and Honors 1983 1990-1992 1998 2001 2003 2005 2006 2010 2011 Outstanding Graduate Award, High School Liceo Gustavo Herrera, Caracas, Venezuela. Graduate Scholarship, Consejo Nacional de Investigaciones Científicas y Tecnológicas, Venezuela. The John Bernard Henry, MD. Endowed Scholarship Award, Graduate School of SUNY. Chair Chemistry Session, Indiana Academy of Sciences Fall Meeting National Science Foundation Faculty Early Career Development (CAREER) Award. The Ball State University 2004 -2005 Award for Outstanding Junior Faculty Member. Gordon Research Conference in Molecular and Cellular Bioenergetics, Discussion Leader. Faculty of Color Award for Research by the Project of New Mexico Graduates of Color. Faculty of Color Award for Mentoring by the Project of New Mexico Graduates of Color. PHS 398/2590 (Rev. 06/09) Page Biographical Sketch Format Page Program Director/Principal Investigator (Last, First, Middle): 2011 2013 2014-2019 2015 Parra, Karlett J. Chair “V-ATPases: Structure, Function and Disease” Session at the Bioenergetics Gordon Research Conference, Proctor Academy in Andover, NH, June. Vice Chair, 2013 Bioenergetics Gordon Research Conference, NH, June. Journal of Biological Chemistry, Editorial Board Chair Elect, Bioenergetics Gordon Research Conference, NH, June. C. Selected Peer-reviewed Publications 1. Karlett J. Parra., and P. M. Kane. “Wild-type And Mutant Vacuolar Membranes Support pH-Dependent Reassembly of the Yeast Vacuolar H+-ATPase In Vitro.” J Biol Chem, 271:19592-9598 (1996). 2. Zhang, J., K. J. Parra, J. Liu, and P. M. Kane. “Characterization Of A Temperature-Sensitive Vacuolar ATPase Mutant with Defects In Bud Morphology and Cytokinesis.” J Biol Chem,273:18470-18480 (1998). 3. Karlett J. Parra., and P. M. Kane. “Reversible Association Between The V1 And Vo Domains of The Yeast Vacuolar H+-ATPase is an Unconventional Glucose-Induced Effect.” Mol Cell Biol, 18: 7064-7074 (1998). 4. Karlett J. Parra, K. Keenan, and P. M. Kane. “The H Subunit (Vma13p) of the Yeast V-ATPase Inhibits the ATPase Activity of Cytosolic V1 Complexes.” J Biol Chem, 275: 21761-21767 (2000). 5. Kane, P. M., and K. J. Parra. “Assembly and Regulation of the Yeast Vacuolar ATPase.” J Exp Biol, 203: 81-87 (2000). 6. Parra-Belky, Karlett J. “Identification of Yeast V-ATPase Mutants by Western Blots Analysis of Whole Cell Lysates.” J Chem Ed, 79: 1348-1350 (2002). 7. Karlett J. Parra-Belky, K. McCulloch, N. Wick, R. Shircliff, N. Croft, K. Margalef, J. Brown, T. Crabill, R. 8. Jankord, and E. Waldo. “Immunoprecipitation of Protein Complexes from Yeast.” Biochem Mol Biol Ed., 33: 289-292 (2005). 9. M. A. Owegi, A. Carenbauer, N. Wick, J. Brown, K. Terhune, S. Bilbo, R. Weaver, R. Shircliff, N. Newcomb, and Karlett J. Parra-Belky. “Mutagenesis Analysis of the Stator Subunit E of the Yeast VATPase.” J Biol Chem, 280: 18393-18402 (2005). 10. M. A. Owegi, D. L. Pappas Jr., M. W. Finch, S. A. Bilbo, C. A. Resendiz, Lori J. Jacquemin, Aswathy Warrier, John D. Trombley, Kathryn M. McCulloch, K. L. M. Margalef, M. J. Mertz, J. M. Storms, C. A. Damin and Karlett J. Parra. “Identification of a domain in the Vo Subunit d that is critical for coupling of the Yeast V-ATPase.” J Biol Chem., 281: 30001-30014 (2006). 11. Ediger, S. D. Melman, D. L. Pappas Jr., M. Finch, J. Applen, and Karlett J. Parra. “The Tether Connecting Cytosolic (N-terminus) and Membrane (C-terminus) Domains of Yeast V-ATPase Subunit a (Vph1) is Required for Assembly of Vo Subunit d”. J Biol Chem, 284:19522-19532 (2009). PMC2740578 12. Karlett J. Parra, M. Osgood, and D. Pappas Jr. “A Research-Based Biochemistry Laboratory Course Designed to Strengthen the Research-Teaching Nexus.” Bio chem Mol Biol Ed.38: 172-179 (2010). 13. Rebecca M. Johnson, Chris Allen, Sandra D. Melman, Anna Wallar, Larry A. Sklar, and Karlett J. Parra. “Inhibitors of Yeast V-ATPase Proton Pumps Identified by HTS Flow Cytometry”, Anal Bioch 15:398(2):203-211 (2010). PMC2853757. 14. Chan CY, Prudom C**, Raines SM**, Charkhzarrin S, Melman SD, De Haro LP, Allen C, Lee SA, Sklar LA, Parra KJ. “Inhibitors of V-ATPase proton transport reveal uncoupling functions of the tether linking cytosolic and membrane domains of the Vo subunit a (Vph1p)”. J Biol Chem (2012). 287(13):10236-50. 15. Parra, KJ. “Vacuolar ATPase (V-ATPase) a Model Proton Pump for Antifungal Drug Discovery”, In Emerging Strategies for Antimicrobial Drug Discovery. GP Tegos and E. Mylonakis (Ed.), CABI,Oxfordshire, UK. In Press. 16. Michel V., Licon-Munoz Y., Trujillo K., Bisoffi M., and Parra K. ““Inhibitors of Vacuolar ATPase Proton Pumps Inhibit Human Prostate Cancer Cell Invasion and Prostate-Specific Antigen Expression and Secretion””. International Journal of Cancer. In Press. 17. Raines SM, Rane H, Bernardo SM, Binder JL, Lee SA, Parra KJ “Deletion of V-ATPase Voa isoforms clarifies the role of vacuolar pH as a determinant of virulence-associated traits in C. albicans”. J Biol Chem 288(9):6190-201 (2013) 18. Rane HS, Bernardo SM, Raines SM, Binder JL, Parra KJ, Lee SA. Candida albicans VMA3 is necessary PHS 398/2590 (Rev. 06/09) Page 2 Biographical Sketch Format Page Program Director/Principal Investigator (Last, First, Middle): Parra, Karlett J. for V-ATPase assembly and function and contributes to secretion and filamentation. Eukaryot Cell Oct;12(10):1369-82. (2013) 19. Hayek SR, Lee SA, Parra KJ. Advances in targeting the vacuolar proton-translocating ATPase (VATPase) for anti-fungal therapy. Front Pharmacol. 5:4 (2014) ** equal contribution D. RESEARCH SUPPORT (last three years) Ongoing Research Support 2P20RR016480-09, NCRR/NIGMS PI: Arterburn J 05/01/2009 - 02/28/2014 NM-INBRE UNM: Subcontract, Role: Investigator Title: V-ATPase Pumps in Prostate Cancer: Regulatory and Functional Studies Overall goals: To study V-ATPase expression and functions in prostate cancer cell lines. 1R01GM086495, NIH/NIGMS PI: Parra K.J. 08/01/2009 - 05/31/2014 Title: V-ATPase H+ Pump Regulation in Fuel Energy Selection Overall goals: The major goals of this project are to identify the metabolic signals that communicate glucose/lipid availability to V-ATPase pumps and to establish the biochemical mechanisms by which glucose regulates V1Vo assembly. 14PRE19020015, AHA_SWA Sponsor: Parra K.J. 01/01/2014 – 12/31/2015 PI: Chan YC Title: Beta-subunit of the yeast PFK complex modulates glucose-dependent reassembly of V-ATPase pumps. Overall goals: Pre-doctoral Fellowship Award. The major goal of this project is to dissect the role of individual PFK subunit for V-ATPase regulation Completed Research Support (Past 3 years) 1R03DA031666, NIH/NIDA PI: Parra K.J. 01/01/2011 - 12/31/2013 Title: Flow Cytometry HTS for Small Molecules that Regulate V-ATPase Proton Transport in Yeast. Overall goals: HTS of the Molecular Libraries Probe Centers Network (MLPCN) library of small molecules to identify V-ATPase inhibitors. NIH-NIGMS; NRSA, (F32) Award PI: De Haro L. Post-Doctoral Fellowship, Role:: Sponsor Title: The Role GADPH in the Regulation of V-ATPase Function (Relinquished) 03/1/2012 - 02/28/2014 Overall goals: To study the cross-talk between GAPDH and glucose-dependent assembly of VATPase 1R01GM086495, NIH/NIGMS PI: Parra K.J. Pre-Baccalaureate Diversity Research Supplement Overall goals: To study vma6 mutants of V-ATPase pumps in yeast. 01/01/2011 - 05/31/2012 1R01GM086495, NIH/NIGMS PI: Parra K.J. 02/04/2010 - 02/03/2012 Postdoctoral Diversity Supplement (Dr. Leyma DeHaro) Overall goals: Dr. De Haro will study regulation of V-ATPase pumps by glycolysis in yeast. UNM-Cancer Center PI: Parra K.J. 04/01/2011 to 08/31/2011 Post-Doctoral Fellowship Matching Funds (Dr. Vera Michel) Title: V-ATPase Pumps in Prostate Cancer Overall goals: Dr. Michel will study the link between V-ATPase and the PSA-AR axis in prostate cancer cell lines. PHS 398/2590 (Rev. 06/09) Page 3 Biographical Sketch Format Page Program Director/Principal Investigator (Last, First, Middle): Parra, Karlett J. 1R01GM086495, NIH/NIGMS PI: Parra K.J. Pre-Baccalaureate Research Supplement (Joshua Sheak) Title: V-ATPase H+ Pump Regulation in Fuel Energy Selection Overall goals: To characterized V-ATPase mutants in yeast. PHS 398/2590 (Rev. 06/09) Page 4 01/01/2010 - 12/31/2012 Biographical Sketch Format Page