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Free Radical Biology and Aging Research Program

Kenneth M. Humphries, Ph.D. Assistant Member, Free Radical Biology and Aging Research Program

Research Interests
My laboratory is primarily interested in understanding how mitochondria produce free radicals in a regulated, limited manner. Excessive mitochondrial production of free radicals is deleterious, and has been implicated in numerous disease processes, including heart disease and diabetes. However, limited mitochondrial free radical production contributes to the normal functioning of the cell through reduction/oxidation (redox) signaling mechanisms. Thus, it is important to block excessive free radical production and oxidative stress without altering basal redox processes. Distinguishing mechanistically how mitochondria produce free radicals during normal versus diseased states will refine approaches to therapeutic antioxidant intervention.

1. A manifestation of many cardiac diseases is cessation of blood flow (ischemia). Ischemia leads to cardiac deficits and if extensive, death, thus making restoration of blood flow imperative. Paradoxically, events that occur when blood flow is restored (reperfusion) contribute to cardiac damage. Oxidative damage, induced by unregulated production of free radicals by impaired mitochondria, is an important contribution to reperfusion injury. Strikingly, brief, repetitive bouts of ischemia/reperfusion can prevent cardiac damage from a subsequent prolonged ischemic event. This phenomenon, termed ischemic preconditioning (IPC), requires the mitochondrial production of free radicals, which contribute to activation of pro-survival signals and ultimately preservation of mitochondrial function. Unlike free radical production associated with reperfusion injury, mitochondrial function is preserved by IPC. Because IPC represents a potentially important mechanism whereby harnessing intrinsic cellular defenses can prevent ischemia/reperfusion injury, a major focus of my lab is to define the molecular mechanisms of this process. The information gained from this research will offer insight into molecular targets that can be pharmacologically manipulated to both minimize reperfusion injury, and to exploit the body’s innate systems of cardioprotection.

2. A major complication and cause of death resulting from types 1 and 2 diabetes is via heart disease. Diabetic cardiomyopathy, like other heart diseases, is associated with deficits in mitochondrial function and increased free radical production. The mechanism(s) whereby diabetes leads to mitochondrial damage and promotes oxidative stress is not fully understood. A goal of our lab is to determine the mechanisms leading to oxidative stress in diabetes by looking at alterations in specific complexes of the electron transport chain. We believe that disease states, such in diabetes, alters the ability of mitochondria to produce free radicals in a regulated manner, and thus causes not only oxidative stress but dysfunction in basal redox biology.

Joined OMRF Scientific Staff in 2008.

Mailing Address
Free Radical Biology and Aging Research Program, MS 21
Oklahoma Medical Research Foundation
825 N.E. 13th Street
Oklahoma City, Oklahoma 73104

Contact Information
Phone: (405) 271-7584
Fax: (405) 271-1437
E-mail: Kenneth-Humphries@omrf.org