Pharmacology and Toxicology
Student Name: Jibran Younis Khokhar
Supervisor: Dr. Rachel F. Tyndale, Endowed Chair in Addictions/Professor, Departments of Pharmacology and Toxicology/Psychiatry
PhD Thesis: An investigation of CYP2B in rat brain: regulation and role in drug and toxin response
Brief Overview: The studies in this dissertation indicate that rat brain CYP2B enzymes are active in vivo and play a meaningful role in the local metabolism of, and the response to, centrally acting substrates (i.e. propofol, chlorpyrifos). These data provide a first demonstration of the important role that brain CYP-mediated metabolism plays in the response to centrally acting substrates (i.e. clinical drugs, toxicants, endogenous neurochemicals), potentially contributing to the inter-individual variability seen in human responses to centrally active drugs and toxicants.
My Ph.D. research examined the role of drug-metabolizing enzymes in the brain in the response to brain acting drugs. I developed a novel rat model of brain cytochrome P450 (CYP) modulation, and using this model showed that brain CYPs are active in vivo and play a meaningful role in the local metabolism of, and the response to, brain acting drugs. In addition to the study of CYP enzymes in the brain, I also studied the role of metabolic cross-tolerance in a rat model of alcohol intake and co-occurring nicotine exposure. During this time, I was awarded a variety of fellowships, including a CIHR Tobacco Use in Special Populations Fellowship, multiple presentation award including the CIHR Gold Award at CSHRF as well as a publication award for "Best Publication in Neuropsychopharmacology." During this time, I published 5 first-author primary publications, 1 high-impact review in Annual Reviews of Pharmacology and Toxicology, and 1 second-author publication.
I am currently a post-doctoral fellow in the Department of Psychiatry at Dartmouth College. In my role at Dartmouth, I have been working toward establishing safer and more efficacious therapeutics for co-occurring schizophrenia and alcohol use disorder. I am also working to develop novel animal models of schizophrenia and alcohol use disorder, while beginning to study the mechanisms underlying alcohol use in these models using behavioral and brain imaging approaches (this work has been funded by a Hitchcock Foundation as well as the Canadian Institute of Health Research) .This work has resulted in 3 co-first-author publications as well as 1 second-author paper, with 2 more papers currently under review. My long-term career goal is to establish an independent line of research studying the mechanisms underlying co-occurring alcohol/substance use disorders and psychiatric illnesses using a variety of behavioral, pharmacological and translational neuroimaging techniques.