Kelly M. Standifer, Ph.D.

Professor and Chair

Pharmaceutical Sciences

Phone (405) 271-6593 x47333

Fax (405) 271-7505

Office CPB 329

Email kelly-standifer@ouhsc.edu

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

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    36. Thakker D R, Ozsoy H Z, Standifer K. Assessing opioid regulation of adenylyl cyclase activity in intact cells. Methods Mol. Med.. 2003; 84 : 29–37

    37. Mandyam C D, Thakker D R, Standifer K. Mu-opioid-induced desensitization of opioid receptor-like 1 and mu-opioid receptors: differential intracellular signaling determines receptor sensitivity. J. Pharmacol. Exp. Ther.. 2003; 306 : 965–972

    38. Bawa T, Altememi G F, Eikenburg D C, Standifer K. Desensitization of alpha 2A-adrenoceptor signalling by modest levels of adrenaline is facilitated by beta 2-adrenoceptor-dependent GRK3 up-regulation. Br. J. Pharmacol.. 2003; 138 : 921–931

    39. Thakker D R, Standifer K. Induction of G protein-coupled receptor kinases 2 and 3 contributes to the cross-talk between mu and ORL1 receptors following prolonged agonist exposure. Neuropharmacology. 2002; 43 : 979–990

    40. Thakker D R, Standifer K. Orphanin FQ/nociceptin blocks chronic morphine-induced tyrosine hydroxylase upregulation. Brain Res. Mol. Brain Res.. 2002; 105 : 38–46

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Grants

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    1. Neuropeptide modulation of cerebral blood flow to improve neurological and psychological outcomes following TBI in the presence. DOD. Start Date: 2023. End Date: 2027.

    2. NOP Receptor Modulator Treatment Optimizes Cognitive, Locomotor, and Sensory Outcomes of mild concussive TBI with and without PTSD. DOD. Start Date: 2023. End Date: 2026.

    3. Evaluation of PPL-138, a NOP/mu partial agonist, for treatment of alcohol abuse in the context of PTSD. DOD. Start Date: 2023. End Date: 2024.

    4. . Non-federal. Start Date: 2022. End Date: 2022.

    5. Pharmacotherapy of Traumatic Brain Injury Accompanied by Hemorrhagic Shock. NIH. Start Date: 2017. End Date: 2022.

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Awards and Honors

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                                                                                            1. OU College of Pharmacy. Richard T. Anderson Endowed Chair in Neuroscience. Date: 2016.  

                                                                                            2. University of Houston College of Pharmacy. Rho Chi Teaching Excellence Award. Date: 2006.  

                                                                                            3. University of Houston College of Pharmacy. Faculty Service Excellence Award. Date: 2005.  

                                                                                            4. American Association of Colleges of Pharmacy Fellow, AACP Faculty Leadership Program. Date: 2004.  

                                                                                            5. University of Houston College of Pharmacy. Faculty Research Excellence Award. Date: 2003.  

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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

                                  
                                                           
                        
                                                
     1. Role: Department Chairperson. Scope: Department. Description: Pharmaceutical Sciences, University of Oklahoma College of Pharmacy. Date: 2009.
                                                
     2. Role: Department Vice-Chair. Scope: Department. Description: Dept Pharmacological & Pharmaceutical Sciences, University of Houston, College of Pharmacy. Date: 2003.