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W. Keith Jones, PhD.
Professor
Ph.D. University of Kentucky, 1987
joneswk@uc.edu
(513)558-2356
Publications
Research
The goal of my research program is the elucidation, at the molecular level, of the signal transduction and gene regulatory events that underlie the development of cardiovascular pathophysiology. Our approach involves the development and utilization of transgenic and gene targeted mice to perturb specific gene regulatory and signal transduction cascades in the heart. This allows us to relate changes in the action of single gene products with specific alterations of cardiac biochemistry, physiology and pathophysiology in vivo.

The focus of the current research in the laboratory is the role played by cytokines, especially TNF-a, and the downstream transcription factor NF-kB in ischemia/reperfusion (I/R) injury, cardiac hypertrophy and heart failure. TNF-a and NF-kB are both involved in the cardiac response to ischemia, and we have shown that genetic ablation (TNF-a) or blockade (NF-kB) of both reduces the extent of myocardial infarction after I/R. We are currently developing reagents for acute blockade of NF-kB.

Similarly, both TNF-a and NF-kB are activated during the development of cardiac hypertrophy in several different murine models that exhibit concentric cardiac hypertrophy, dilated cardiomyopathy and heart failure. It is well known that TNF-a is upregulated in patients with heart failure, but the cause and effect relationship between these factors and specific cardiac pathophysiology is currently a matter of great debate. We are employing unique transgenic mouse strains that block the action of these molecules to conclusively determine their roles in cardiac The hope is that understanding the mechanisms of pathophysiology at the molecular level will facilitate the development of novel pharmacological and/or gene therapeutic strategies to fight heart disease.
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