Kenneth Humphries, PhD

Biography

"My first research experiences came as an undergraduate when I worked first in an analytical chemistry laboratory at John Carroll University, and then as a summer undergraduate research student at neighboring Case Western Reserve University. This latter experience launched my research career, as I subsequently attended graduate school at CWRU. My dissertation research focused on understanding how oxidative stress affects cardiac mitochondrial function. I elucidated at the molecular level how the lipid peroxidation product, 4-hydroxynonenal, disrupts mitochondrial respiration. This work was impactful because while oxidative stress had been widely implicated in numerous diseases and aging, specific targets remained elusive. My two papers describing this mechanism have been cited over 600 times, combined. I continued pursuing my interest in oxidative stress and redox biology during my postdoctoral training at UCSD. I discovered a novel mechanism whereby cAMP dependent protein kinase (PKA) is regulated by oxidation and reduction. PKA is one of the most studied protein kinases because of its importance in numerous cellular functions and tissues, and thus this work had broad implications. Starting my own lab at the Oklahoma Medical Research Foundation, I combined my interests and expertise in mitochondrial and redox biology to understand how diabetes affects the heart. We discovered that a type of protein modification, called lysine acetylation, is abundant in the mitochondria of the diabetic heart. We found that this protein modification impacts how the heart derives energy because it decreases mitochondrial pyruvate uptake. We have also continued to focus on cardiac PKA signaling and how it is affected by diabetes. Our studies have elucidated that the metabolic target of PKA, phosphofructokinase-2, is dysregulated with diabetes. PFK-2 normally increases glycolysis when phosphorylated, and thus its aberrant phosphorylation may be an important means whereby diabetes affects cardiac metabolic flexibility. Our current studies have focused on targeting glycolysis as a means of normalizing metabolic flexibility, mitigating diabetic cardiomyopathy, and determining how it affects cardiac aging."

Email

kenneth-humphries@omrf.org

Publications

Research Interests:

• Cardiac Metabolism
• Mitochondria
• Diabetes
• Cardiac Aging
• Redox Signaling
• Oxidative Stress