Office: VBRB 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.
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.
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,
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,
Angiotensin II-mediated microvascular thrombosis. Hypertension. 2010
Wright JW, Harding JW.
The brain RAS and Alzheimer's disease. Exp Neurol. 2010
PubMed Publications (Note: This PubMed link may produce additional "JW