B.S., 1994, Chemistry, Northern Michigan University
Ph.D., 2004, Pharmacology and Toxicology, University of Arizona
Postdoctoral, 2001-2005, Medical Pharmacology, School of Medicine, University of Arizona
Dr. Witt received a BS in chemistry from Northern Michigan University and a PhD in pharmacology and toxicology from the University of Arizona, College of Medicine.
My research interests are in two interconnected areas, the evaluation of CNS therapeutics for the treatment of neurodegenerative diseases, and blood-brain barrier alterations associated with age and disease.
1) A heavy focus in my laboratory is the evaluation of novel selective somatostatin receptor subtype-drug agonists to mitigate age-dependent learning and memory deficits in models of Alzheimer’s disease. The primary goal of this this work is to advance an orally bioavailable first-in-class somatostatin receptor subtype selective drug candidate for cognitive enhancement and potential disease-modifying attributes. This is an extremely exciting area, with numerous potential points for collaboration. Given the current state of therapeutic options, any viable approach that is not redundant with current medications would be of great benefit to Alzheimer’s patients and their families. Other avenues of study have also resulted from the ongoing work, with increased interest respective to somatostatin related actions on microglia induced inflammatory events.
2) Another area of research interest is in the field of blood-brain barrier (BBB) alterations with pro-inflammatory high-fat “Western” diets. The BBB represents the principle interface between peripheral and central nervous system. Obesity associated with increased peripheral inflammation and numerous co-morbidities holds significant ramifications respective to BBB integrity and CNS disease outcomes. Alterations in diet/metabolism shown to mitigate BBB tight junction protein regulation and integrity may have broad reaching implications. Correspondingly, the potential benefit of key omega-3 polyunsaturated fatty acids (PUFAs) on BBB tight junctions remains to be fully investigated. There are also pharmacological connections, respective to peroxisome proliferator-activated receptor-γ activation and dietary fat interactions, which hold a good deal of interest to the research and health-care community.
National Institute of Neurological Disorders and Stroke-NIH, role: Principle Investigator. Title: Dietary impact on blood-brain barrier tight junctions (8-1-2015 thru 7-31-2017).
National Institute of Aging-NIH, R01, role: Principle Investigator. Title: Lead Optimization of Somatostatin-based Therapeutic for Alzheimer's Disease (6-15-2015 thru 6-14-2020).
Society for Neuroscience (SFN), 1998-present
American Society of Pharmacology & Experimental Therapeutics (ASPET), 1998-present
Alzheimer's Association, 2012-present
Academic Drug Discovery Consortium (ADDC), 2013-present
Sandoval K.E., Farr S.A., Banks W.A., Crider A.M., Morely J.E., and Witt K.A. Somatostatin receptor-4 agonist NNC 26-9100 induced learning and memory enhancement corresponding with ApoE4 transgenic mice (in progress).
Witt K.A., Sandoval K.E., Harris M., and Wooten. Blood-brain barrier tight junctional alterations with Omega-3 fatty acid vs. lard based diets (in progress).
Witt K.A. and Sandoval K.E. Steroids and the blood-brain barrier: Therapeutic Implications. Pharmacology of the Blood Brain Barrier: Targeting CNS disorders. Adv Pharmacol. 2014;71:361-90.
Sandoval K.E., Witt K.A., Crider A.M., Kontoyianni M. Somatostatin Receptor-4 Agonists as Candidates for Treatment of Alzheimer’s Disease. Frontiers in Drug Design and Discovery, 2014, chapter-7, vol. 6.
Sandoval K.E., Farr S.A., Banks W.A., Crider A.M., Morely J.E., and Witt K.A. Somatostatin receptor subtype-4 agonist NNC 26-9100 mitigates the effect of soluble Aβ42 oligomers via a metalloproteinase-dependent mechanism, Brain Research, 2013, Jul, 3, 1520: 145-156.