Faculty Biography

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Wallace L. McKeehan received his undergraduate degree in chemistry at the University of Florida and Ph.D. in chemistry at the University of Texas-Austin. He joined IBT from the W. Alton Jones Cell Science Center in Lake Placid, NY, where he was deputy director and senior scientist and was co-founder of Upstate Biotechnology, Inc. He held adjunct faculty posts at the University of Vermont and Clarkson University. Now he directs the Institute of Biosciences and Technology's Center for Cancer Biology and Nutrition and holds the J.S. Dunn Endowed Chair. He is a professor in the Department of Biochemistry and Biophysics, Texas A&M University, and a member of Texas A&M's Graduate Faculty of Nutrition and the Graduate Faculty of Biomedical Sciences at the University of Texas-Houston and Adjunct Professor in Molecular and Cellular Biology at Baylor College of Medicine.

Research Interests of Wallace L. McKeehan, Ph.D. -- Molecular and cell biology of signal transduction
Our laboratory studies how the chemical signals (polypeptide growth factors and cytokines) in the local tissue environment control growth and specialization of different cell types of the prostate, the liver, the vascular system, and neural tissue. These signals determine the normal development and function of the tissues while aberrations result in tissue dysfunctions and diseases, such as cancer, stroke, atherosclerosis, liver and neural disease. These signaling systems-- which are composed of a signal polypeptide from one cell type and a reception system on another -- are the basis for communication among cells in tissues, but also they serve as sensors of signals like hormones and nutrients that come from outside tissues. The cellular reception system for many signal polypeptides consists of a transmembrane protein whose external domain interacts with signal polypeptides and an intracellular domain which is a protein kinase enzyme which activates metabolic pathways that control cell growth, function, and gene expression.

The Fibroblast Growth Factor (FGF) and Transforming Growth Factor (TGF) Beta families of intrinsic tissue regulators are at the heart of homeostasis within adult tissues and in embryogenesis. The FGF family is particularly interesting because it is intimately interwoven with the peri-cellular matrix through heparan sulfate proteoglycans which are an integral part of the signaling system. The system senses changes in the local environment and transmits them to the interior cells for a response.

Our laboratory seeks to understand the molecular mechanisms of assembly of components of the FGF and TGF beta signaling systems, their role in homeostasis of prostate, liver and the cardiovascular systems and their dysfunction that results in disease. Technologies employed in the laboratory include recombinant DNA technologies, protein chemistry, expression of recombinant proteins in bacteria, yeast, insect cells and mammalian cells, primary cell culture and tissue reconstitution, monoclonal antibodies and hybridomas and mouse transgenics.

Dr. McKeehan's laboratory also studies the mechanism of action of potential tumor suppressor RASSF1 through a novel complex (LRPPRC) that integrates the microtubular cytoskeleton and mitochondria with chromosome remodeling, genetic stability and apoptosis. The laboratory also studies the mechanism of action of active components in foods and edible plants that impinge on signal transduction pathways, genetic stability and tumor suppression and have potential value in prevention or therapeutic intervention of disease particularly cancer.

Representative Publications

Yu, C., F. Wang, M. Kan, C. Jin, R.B. Jones, M. Weinstein, C. Deng, and W.L. McKeehan (2000) Elevated cholesterol metabolism and bile acid synthesis in mice lacking membrane tyrosine kinase receptor FGFR4. J. Biol. Chem. 275: 15482-15489.

Jones, R.B., F. Wang, Y. Luo, C. Yu, C. Jin, T. Suzuki, M. Kan and W. L. McKeehan. (2001) The nonsense-mediated decay pathway and mutually exclusive expression of alternatively spliced FGFR2IIIb and IIIc mRNAs. J. Biol. Chem. 276: 4158-4167.

Ye, S., Y. Luo, W. Lu, R.B. Jones, R.J. Linhardt, I. Capila, T. Toida, M. Kan, H. Pelletier and W.L. McKeehan (2001) Structural basis for interaction of FGF-1, FGF-2 and FGF-7 with different heparan sulfate motifs. Biochemistry 40: 14429-14439.

Yu, C., F. Wang, C. Jin, X. Wu, W. Chan and W.L. McKeehan (2002) Increased carbon tetrachloride-induced liver injury and fibrosis in FGFR4-deficient mice. Am. J. Pathol. 161: 2003-2010.

Liu, L., A. Vo, G. Liu and W.L. McKeehan (2002) Novel complex integrating mitochondria and the microtubular cytoskeleton with chromosome remodeling and tumor suppressor RASSF1 deduced by in silico homology analysis, interaction cloning in yeast and colocalization in cultured cells. In Vitro Cell. Devel. Biol. Animal 38:582-594.

Complete On-line Library of Medicine Publications with Abstracts