Professor of Pharmacology and Chair
Department of Pharmaceutical Sciences
Dr. Kelly Standifer joined the College of Pharmacy as Professor of Pharmaceutical Sciences. Her research interests, ultimately, is to develop alternative therapeutic options (to morphine) for the treatment of severe pain. The newest member of the opioid receptor family, opioid receptor like-1 receptor (ORL1), and its endogenous agonist, orphanin FQ/nociceptin (OFQ/N), have been strongly implicated in the development of morphine tolerance. Chronic morphine treatment increases levels of OFQ/N; blocking the actions of OFQ/N significantly reduce the extent to which the analgesic actions of morphine are reduced. Using human neuronal cell lines that natively express mu and ORL1 receptors, we study the cellular mechanisms of ORL1 and mu opioid receptor activation (by the endogenous peptides OFQ/N and Dynorphin, and the synthetic agonists, DAMGO and morphine), and the cellular mechanisms of ORL1- and mu opioid receptor-mediated mu and ORL1 tolerance and cross-tolerance. Acutely, OFQ/N activates protein kinase C (PKC), which activates and translocates G protein-coupled receptor kinase 2 (GRK2) and GRK3 to the cell membrane where GRK2 can quickly desensitize the mu opioid receptor in the presence of a mu opioid agonist such as morphine. Our next step is to determine where these changes occur in vivo, and how they might be manipulated to reduce the extent of morphine tolerance development.
ORL1 desensitization is produced by GRK3. Tolerance induced by prolonged exposure to OFQ/N and/or morphine treatment also involves GRK. Similar to morphine, prolonged OFQ/N treatment (24 h or more) upregulates GRK levels. Ultimately, though, it is the increased availability of GRK that produces the rapid tolerance and/or cross-tolerance upon challenge with an agonist. We are in the process of studying ORL1 phosphorylation sites, and how mutation of these sites affects receptor function.
Education & Experience
- PhD, University of Florida, Gainesville, FL, 1988
- B.S. Zoology, Duke University, Durham, NC, 1984
- Associate Natural Science, St. Gregory's College, Shawnee, OK, 1982
- Postdoctoral Fellowship, Memorial Sloan-Kettering Cancer Center, NY, NY Opioid Receptor isolation and purification - Supervisor: Gavril W. Pasternak, M.D., Ph.D., 1988-1990
- Research Associate, Program in Molecular Pharmacology and Therapeutics, Memorial Sloan-Kettering Cancer Center, New York, NY, 10021, 1991- 1992
- Vice-Chair, Dept. of Pharmacological and Pharmaceutical Sciences, University of Houston, College of Pharmacy, 2003-2006
- Director, Graduate Studies, Dept. of Pharmacological and Pharmaceutical Sciences, University of Houston, College of Pharmacy, 2003-2006
- Associate Professor of Pharmacology, Dept. of Pharmacological and Pharmaceutical Sciences, University of Houston College of Pharmacy, 2001-2006
- Assistant Professor of Pharmacology, Dept. of Pharmacological and Pharmaceutical Sciences, University of Houston College of Pharmacy, Houston, TX, 1995-2001
- Assistant Laboratory Member, Program in Molecular Pharmacology and Therapeutics, Memorial Sloan-Kettering Cancer Center, New York, NY, 1992-1995
Honors & Service
- 1993-Present: Society on NeuroImmune Pharmacology
- 1993-Present: Rho Chi
- 1993-Present: Sigma Xi
- 1993-Present: American Society for Pharmacology and Experimental Therapeutics
- 1993-Present: American Association of Colleges of Pharmacy
- 1993-Present: International Narcotics Research Conference
- 1993-Present: Society for Neuroscience
- Outstanding Alumnus - St. Gregory's College (1992)
- Faculty Achievement Award - College of Pharmacy, UH (1996)
- Awarded The Scientist’s (10:15,1996) “hot paper” status for: Standifer, KM et al., Neuron 12:805-810, 1994.
- Faculty Achievement Award, College of Pharmacy, UH (2001)
- Promotion to Associate Professor with tenure, UH (2001)
- Inducted into the Rho Chi Honor Society, Beta Omicron Chapter (UH 2003)
- Faculty Research Excellence Award, UH College of Pharmacy (2003)
- Selected as a Fellow in the AACP Faculty Leadership Program (Aug 2004;
- “graduated” July 2005)
- Faculty Service Excellence Award, UH College of Pharmacy (2005)
- Rho Chi Teaching Excellence Award, UH College of Pharmacy (2006)
Selected Publications & Presentations
Zhang Y, Donica CL, Standifer KM. Sex differences in the nociceptin/orphanin FQ system in rat spinal cord following chronic morphine treatment. Neuropharmacol 2012; 63: 427-433.
Greenwood-Van Meerveld B, Standifer KM. Methylnaltrexone in the treatment of opioid-induced constipation. Clin Exper Gastroenterol 2008; 1: 49-58.
Thakker DR, Altememi GF, Mandyam CD, Ibrahim H, Ramirez VI, Standifer KM. Naloxone benzothydrazone activates extracellular signal-regulated protein kinases and modulates nociceptin opioid peptide receptor activity. Am J Pharmacol Toxicol 2007; 2(2): 51-59.
Bawa T, Altememi GF, Mandyam CD, Schwaarz LA, Eikenburg DC, Standifer KM. Sensitivity of alpha(2)-adrenoceptors to desensitization after chronic epinephrine treatment incrases in the presence of beta(2)-adrenoceptors. BMC Pharmacol 2007; 7:16.
Salim S, Standifer KM, Eikenburg DC. ERK1/2 mediated transcriptional regulation of GRK3 expression in neuronal cells. J Pharmacol Exp Ther 2007; 321: 51-59.
Current Grants Awarded
Oklahoma Center for the Advancement of Science and Technology (OCAST) - Orphanin FQ regulates tyrosine hydroxylase expression
Department of Defense (DoD) - Blockade of nociceptin signaling reduces biochemical, structural and cognitive deficits after traumatic brain injury
Department of Defense (DoD) - Molecular mechanism of chronic pain and its modulation by post-traumatic stress disorder andnociceptin/orphanin FQ
NIH - Cellular mechanisms of opioid receptor-like 1 (ORL1) regulation and cross talk
9/1/2007 - 8/31/2008 Presbyterian Health Foundation (PHF) - Orphanin FQ/Nociceptin (OFQ/N) mediation of morphine tolerance