1. Role: Department Chairperson. Scope: Department. Description: Pharmaceutical Sciences, University of Oklahoma College of Pharmacy. Date: 2009.
Kelly M. Standifer, Ph.D.
Professor and Chair
Pharmaceutical Sciences
Phone (405) 271-6593 x47333
Fax (405) 271-7505
Office CPB 329
Summary
Our research goals are to develop a therapeutic treatment for traumatic brain injury (TBI) and co-morbid conditions such as post-traumatic stress disorder (PTSD), impaired learning and memory and pain. The newest member of the opioid receptor family, nociceptin/orphanin FQ peptide receptor (NOP; also known as ORL1 and KOR3), and its endogenous agonist, nociceptin/orphanin FQ (N/OFQ), bi-directionally modulate CNS and immune system functions, including (but not limited to) pain sensitivity, anxiety, cognition and monocyte chemotaxis. N/OFQ appears to function as a physiological modulator, trying to restore homeostasis. Over the last 15 years, our lab has examined the role of N/OFQ/NOP in three devastating physiological conditions: TBI, PTSD and chronic pain. We found that N/OFQ levels increase in various brain regions, CSF and/or serum over time following TBI, traumatic stress or chronic nerve injury. We hypothesize that the N/OFQ/NOP system becomes dysregulated, either in response to, or because of these conditions. We’ve employed a variety of approaches to study receptor activity and NOP/N/OFQ expression in vitro and in vivo. This includes use of cell lines from different cell types, and male and female rats that express functional or non-functional NOP receptors. We found that elevated levels of N/OFQ are associated with vestibular deficits following TBI, and with allodynia following exposure to a traumatic stress. A single, acute injection of NOP antagonist within 30 min of TBI delayed the appearance of vestibular deficits but prevented the development of oxidative damage 9 days later (Awwad et al., 2018). Similarly, administration of NOP antagonist 7 days following exposure to traumatic stress reverses persistent hyperalgesia caused by traumatic stress (Zhang et al., 2015). Loss of a functional NOP receptor in male rats was protective from traumatic stress-induced hyperalgesia, failed to provide the same relief in female rats (Zhang et al., 2019), and reduced the severity and recovery time from TBI in male and female rats (Al Yacoub et al., 2024). As a result, we utilize two different models of TBI (focal impact and concussive) and a model of PTSD to interrogate the ability of NOP receptor partial agonists prevent or reverse TBI- and/or PTSD-induced vestibular and cognitive deficits, anxiety-like behaviors and hyperalgesia.
Publications & Presentations
- 51. Ryan-Moro J, Chien C C, Standifer K, Pasternak G W. Sigma binding in a human neuroblastoma cell line. Neurochem. Res.. 1996; 21 : 1309–1314
52. Ciszewska G R, Ginos J A, Charton M, Standifer K, Brooks A I, Brown G P, Ryan-Moro J P, Berzetei-Gurske I, Toll L, Pasternak G W. Synthesis and characterization of substituted benzoylhydrazones of naloxone. Synapse. 1996; 24 : 193–201
53. Standifer K, Rossi G C, Pasternak G W. Differential blockade of opioid analgesia by antisense oligodeoxynucleotides directed against various G protein alpha subunits. Mol. Pharmacol.. 1996; 50 : 293–298
54. Brooks A I, Standifer K, Rossi G C, Mathis J P, Pasternak G W. Characterizing kappa3 opioid receptors with a selective monoclonal antibody. Synapse. 1996; 22 : 247–252
55. Standifer K, Jenab S, Su W, Chien C C, Pan Y X, Inturrisi C E, Pasternak G W. Antisense oligodeoxynucleotides to the cloned delta receptor DOR-1: uptake, stability, and regulation of gene expression. J. Neurochem.. 1995; 65 : 1981–1987
Grants
- 16. Molecular mechanisms of chronic pain and its modulation by posttraumatic stress disorder and Nociceptin/Orphanin FQ. DOD. Start Date: 2011. End Date: 2015.
Awards and Honors
- 11. St. Gregory's College. Outstanding Alumna. Date: 1992.
Education
- 1. Degree: Postdoctoral Training. Memorial Sloan-Kettering Cancer Center. Date: 1990.
2. Degree: Ph D. University of Florida . Date: 1988.
3. Degree: BS. Duke University. Date: 1984.
4. Degree: Associate of Natural Science. St. Gregory's College. Date: 1982.
Administrative Assignments
2. Role: Department Vice-Chair. Scope: Department. Description: Dept Pharmacological & Pharmaceutical Sciences, University of Houston, College of Pharmacy. Date: 2003.