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School of Pharmacy
School of Pharmacy
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Ken Witt, PhD

Associate Professor of Pharmaceutical Sciences

Phone: 618-650-5144
Fax: 618-650-5145
E-mail: kwitt@siue.edu


Pharmacology

BS, 1994, Chemistry, Northern Michigan University

PhD, 2004, Pharmacology and Toxicology, University of Arizona

Postdoctoral, 2001-2005, Medical Pharmacology, School of Medicine, University of Arizona


RESEARCH

My ongoing research focuses on pharmacological avenues in which to mitigate central nervous system diseases. Principle projects center on somatostatin involvement in learning and memory, with evaluation of somatostatin receptor subtype agonists for the mitigation of cognitive decline associated with Alzheimer’s disease. Our team has made great strides in the arena in the design and evaluation of therapeutics aimed to treat cognitive dementia, identifying the somatostatin receptor subtypes as a viable target.

Other research interests include: blood-brain barrier (BBB) alterations under pathological stress; BBB tight junctional complex, estrogenic effects on BBB tight junctions, and CNS drug delivery.

Current Projects:

  • Evaluation of novel selective somatostatin receptor subtype-drug agonists to mitigate age-dependent learning and memory deficits in models of Alzheimer’s disease
  • Role of Apolipoprotein E-ε4 in regulation of somatostatin levels, somatostain receptor alterations and neprilysin activity
  • Hormonal impact on enzymatic regulation in the CNS disease

Research Support (external)

  • Research and development (NIH-NIA), R21, 2009-2012
  • Research and drug development (Alzheimer’s Drug Discovery Foundation), 2007-2009
  • National research service award (NIH-NINDS), F32, 2002-2005

Patents

Methods for Treating Memory Impairment. Application #: 13/502,364, filed April 2012.

Selected Publications

K.E. Sandoval , K.A. Witt , A.M. Crider, M. Kontoyianni. Somatostatin Receptor-4 Agonists as Candidates for Treatment of Alzheimer’s Disease. Frontiers in Drug Design and Discovery (Invited book chapter, submitted).

R.D. Egleton, K.A. Witt, and T.P. Davis. Opioids. Handbook of Biologically Active Peptides, AJ Kastin ed., 2nd edition, Elsevier (Invited book chapter, in press).

X. Wang, D. Mealer, L. Rodgers, K. Sandoval, K. Witt, C. Stidsen, M. Ankersen, A. M. Crider. Synthesis of 2-Thiohydantoins as Somatostatin Receptor Ligands (Letters in Drug Design and Discovery, 2012, 9 (7):655-662.

K.E. Sandoval, S.A. Farr, W.A. Banks, A.M. Crider, J.E. Morely, and K.A. Witt. Somatostatin Receptor Subtype-4 Agonist NNC 26-9100 Decreases Extracellular and Intracellular Aβ1-42 Trimers. Eur J Pharmacol 2012 May 15;683(1-3):116-24.

K.E. Sandoval, S.A. Farr, W.A. Banks, M. L. Niehoff, J.E. Morley, A.M. Crider, and K.A. Witt. Chronic peripheral administration of somatostatin receptor subtype-4 agonist NNC 26-9100 enhances learning and memory in SAMP8 mice Eur J Pharmacol. 2011 Mar 1;654(1):53-9.

K.E. Sandoval and K.A. Witt. Age and 17β-estradiol effects on blood-brain barrier tight junction and estrogen receptor proteins in ovariectomized rats. Microvasc Res. 2011 Mar;81(2):198-205.

A.M. Crider, M. J. Nieto, and K. A. Witt. Central Dopaminergic Signaling Agents: Wilson & Gisvold's Textbook of Organic Medicinal and Pharmaceutical Chemistry (12th ed.), Lippincott, Williams & Wilkins, 2011, pg.471-490.

K.A. Witt, P. T. Ronaldson, K. E. Sandoval, and T. P. Davis. Central Nervous System Delivery of Peptides across the Blood-Brain Barrier: Humana Press: Neuroscience Methods Series. Ed. K.K.Jain. 2010, pg.233-248.

K.E. Sandoval and K.A. Witt. Blood-Brain Barrier Tight Junction Permeability and Ischemic Stroke Neurobiology of Disease, 2008, Nov;32(2):200-19. 

K.A. Witt, K.S. Mark, K.E. Sandoval, and T.P. Davis. Reoxygenation stress on blood-brain barrier paracellular permeability and edema in the rat. Microvascular Research, 2008 Jan;75(1):91-6.

A. M. Crider and K.A. Witt. Somatostatin sst4 Ligands: Chemistry and Pharmacology. Mini-reviews in Medicinal Chemistry, 2007, 7, 213-220.

K.A. Witt, and T.P. Davis. CNS Drug Delivery: Opioid Peptides and the Blood-Brain Barrier. AAPS Journal, 2006 Feb; 8(1): E76-E88.

K.A. Witt, K.S. Mark, J.D. Huber, and T.P. Davis. Hypoxia Inducible Factor and Nuclear Factor Kappa-B Activation in Blood-Brain Barrier Endothelium Under Hypoxic/Reoxygenation Stress J. Neurochem., 2005 Jan;92(1):203-14.

R.D. Egleton, K.A. Witt, and T.P. Davis. Peptides and the BBB Enhancing Peptide Bioavailability to the brain: Blood-Spinal Cord and Brain Barriers in Health and Disease. H. S. Sharma & J. Westman (eds.) Academic Press, pg 107-115 (2004).

J.D. Huber, C.R. Campos, R.D. Egleton, K.A. Witt, L. Guo, M.J. Roberts, M.D. Bentley, T.P. Davis. Conjugation of low molecular weight poly(ethylene glycol) to biphalin enhances antinociceptive profile. J Pharm Sci. 2003 Jul;92(7):1377-85.

K.A. Witt, K.S. Mark, S. Hom, and T.P. Davis. Effect of hypoxia/reoxygenation on rat blood-brain barrier permeability and tight junctional protein expression. Am. J. Physiol. Heart Circ. Physiol.. 2003 Dec;285(6):H2820-31.

K.A. Witt, J.D.Huber, R.D.Egleton, and T.P.Davis. Pluronic P85 Copolymer Enhances Opioid Peptide Analgesia. J. Phar. Exp. Ther. 2002 Nov;303(2):760-7.

J.D. Huber, K.A. Witt, S. Hom, R.D. Egleton, K.S. Mark, and T.P. Davis. Peripheral Inflammatory Pain Induces Blood-Brain Barrier Tight Junction Reorganization. Am. J. Physiol. Heart Circ. Physiol. 2001 Mar;280(3):H1241-248.

K.A. Witt, J.D. Huber, R.D. Egleton, M. J. Roberts, M. D. Bentley, L. Guo, H. Wei, H. I. Yamamura and T.P. Davis Pharmacodynamic and Pharmacokinetic characterization of poly(ethylene glycol) conjugation to met-enkephalin analog [D-Pen2, D-Pen5]-enkephalin (DPDPE). J. Pharm. Exp. Ther. 2001 Aug;298(2):848-56.

K.A. Witt, T.J.Gillespie, J.D. Huber, R.D. Egleton, and T.P. Davis. Pepide Drug Modification to Enhance Bioavailability and Blood-Brain Barrier Permeability. Peptides 2001 Dec;22(12):2329-43.

K.A. Witt, C.A. Slate, R.D. Egleton, J.D. Huber, H.I. Yamamura, V.J. Hruby, and T.P. Davis. Assessment of Stereoselectivity of Trimethylphenylalanine Analogs of -Opioid [D-Pen, D-Pen2,5] Enkephalin. J. Neurochem. 2000 Jul; 75(1):424-35.

K.A. Witt, R.D.Egleton, J.D. Huber, V.J. Hruby, and T.P. Davis. Blood-Brain Barrier Permeability Assessment of Stereoselective Opioid Analogues. British J. Pharm. 2000 Oct; 131: suppl. 122.

K.A. Witt, J.D. Huber, R.D. Egleton, and T.P. Davis. Insulin Enhancement of Opioid Peptide Transport Across the Blood-Brain Barrier and Assessment of Analgesic Effect. J. Pharm. Exp. Ther. 2000 Dec; 295(3):972-978.