College of Veterinary Medicine

Research in IPN

Joseph W. Harding, Ph.D.

  Joseph Harding

Office: VBR rm. 471
Phone: (509) 335-7927

The primary objective in my laboratory is to develop peptide- and peptidomimetic-pharmaceuticals for the treatment of dementia, cancer, and deficits in wound healing.  The common theme linking these disorders is dysfunction related to tissue remodeling. In dementia this dysfunction manifests as a lack of neuronal connectivity; in cancer it is exemplified by abnormal vascularization of the tumors and the ability of cancer cells to escape the primary tumor and metastasize to distance sites, and in deficient wound repair it is reflected in an inability of cells to invade the wound area. Interestingly the same regulatory proteins mediate the remodeling aspects of each of these disorders.

Our laboratory is interested in understanding the fundamental processes that underlie alterations in tissue structure and the growth factors that direct these processes. We are particularly interested in a family of enzymes called matrix metalloproteinases that regulate the dynamic composition of the extracellular matrix and the hepatocyte growth factor/ c-Met (its receptor) system, which is the premier regulator of cell migration. Based on these targets and using computer aided design and organic synthesis methodologies we have successfully generated molecules with potent cognitive enhancing activity, anti-cancer activity, and the ability to speed dermal wound repair. Our current work is focused on understanding the molecular mechanism of action of these putative drugs, designing new drug candidates with superior bioavailability characteristics, and identifying new therapeutic uses for these molecules.

Biographical Information

Joseph W. Harding, Professor, completed his B.S in chemistry at Allegheny College in 1970 and Ph.D. in chemistry at the University of Delaware in 1974. He was a postdoctoral fellow in neurochemistry with Frank Margolis at Roche Institute of Molecular Biology in 1974-76 and has been at Washington State University since 1976.

Recent Publications

Wright, J.W. and Harding, J.W.  (2008)  The angiotensin AT4 receptor subtype as a target for the treatment of memory dysfunction associated with Alzheimers disease.  Journal of the Renin-Angiotensin-Aldosterone Systems, 9:226-237.

Wright JW, Yamamoto BJ, Harding JW.  (2008)  Angiotensin receptor subtype mediated physiologies and behaviors: new discoveries and clinical targets.  Prog Neurobiol., 84: 157-181.

Wright, J.W., Meighan, P.C., Davis, C.J., Olson, M.L., Weidiger, R.S., and Harding, J.W.  (2009) Habituation-induced neural plasticity in the hippocampus and prefrontal cortex mediated by MMP-3. Behavioral Brain Research, 203(1): 27-34.

Wilson, W.L., Munn, C., Ross, R.C., Harding, J.W., and Wright, J.W. (2009) The role of the AT4 and cholinergic systems in the nucleus basalis magnocellularis (NBM): Effects on spatial memory. Brain Research, 1272: 25-31. 

Yamamoto BJ, Elias PD, Masino JA, Hudson BD, McCoy AT, Anderson ZJ, Varnum MD, Sardinia MF, Wright JW, Harding JW. The angiotensin IV analog Nle-Tyr-Leu-psi-(CH2-NH2)3-4-His-Pro-Phe (norleual) can act as a hepatocyte growth factor/c-Met inhibitor. J Pharmacol Exp Ther. 2010 Apr;333(1):161-73.

Senchenkova EY, Russell J, Almeida-Paula LD, Harding JW, Granger DN. Angiotensin II-mediated microvascular thrombosis. Hypertension. 2010 Dec;56(6):1089-95.

Wright JW, Harding JW. The brain RAS and Alzheimer's disease. Exp Neurol. 2010 Jun;223(2):326-33.

PubMed Publications (Note: This PubMed link may produce additional "JW Harding" authors.)

Last Edited: Jul 09, 2013 9:24 AM   

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