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Szweda, Luke I.

Luke I. Szweda, Ph.D.

Luke I. Szweda, Ph.D.

Member and Program Chair

Hille Family Foundation Chair in Neurodegenerative Disease Research

Adjunct Professor, Department of Biochemistry and Molecular Biology, Department of Geriatric Medicine, Reynolds Oklahoma Center on Aging, and Department of Medicine, Section of Endocrinology and Diabetes, University of Oklahoma Health Sciences Center

Visiting Professor, Department of Biochemistry, Univercite Paris 7, Paris, France

A continuous supply of energy is required for life. We derive energy from the air we breathe and the food and water we consume. Mitochondria present within the cells of our bodies are responsible for coordinating the production of energy. However, much like a coal plant that produces toxic byproducts, mitochondria also generate free radicals that can damage components of the cell. Paradoxically, free radicals are also capable of regulating mitochondrial function to prevent damage.

In my laboratory, we seek to define how free radicals normally control mitochondrial function and how disruption of these processes as we age negatively impacts heart function. Heart disease is a leading cause of death and debilitation, particularly in the elderly. Our studies could therefore lead to the development of therapeutic strategies that diminish or prevent the progression of heart disease and positively impact life in an increasing elderly population.

Education
B.A. Chemistry, Carleton College, Northfield, Minnesota, 1982
Ph.D. Biochemistry, University of California, Los Angeles, 1990
Postdoctoral Fellow, National Institutes of Health, Bethesda, Maryland, 1990-1994

Other Activities
Member, NIH Study Section, Cellular Mechanisms in Aging and Development, 2003-Present
Chair, AHA, Committee 4, Mid-America Research Study Section, 2002-2004
Member, AHA, Mid-America Research Study Section, 1998-2004
Editorial Board, Archives of Biochemistry and Biophysics, 1995-Present

Memberships
American Association for the Advancement of Science
American Chemical Society
American Society of Biochemistry and Molecular  Biology
American Heart Association
Society for Free Radical Biology and Medicine

Joined OMRF Scientific Staff in 2005.

Cardiovascular disease, characterized by loss of myocardial function and, in the long term, development of heart failure, is a leading cause of debilitation and death in an increasingly obese and elderly population.  Required for the maintenance of cardiac energy status and function, mitochondria exhibit increases in the production of oxygen-derived free radicals and deficits in function during the progression of cardiovascular disease.  Free radical species can induce irreversible oxidative damage but are also capable of altering protein function reversibly, thereby acting as regulatory molecules.  Our research seeks to define biochemical mechanisms by which alterations in redox status regulate mitochondrial function and age- and obesity-related alterations that promote the progression to irreversible oxidative damage and loss in viability.  We utilize biophysical, biochemical and physiological approaches to define targets, mechanisms, and metabolic consequences of oxidative modification.  Information gained from these studies is required to delineate pathways and physiological implications of redox regulation and for the development of effective strategies to treat and/or prevent the progression of cardiovascular disease.

Recent Publications

* Yao L, Heuser-Baker J, Herlea-Pana O, Zhang N, Szweda LI, Griffin TM, Barlic-Dicen J. Deficiency in adipocyte chemokine receptor CXCR4 exacerbates obesity and compromises thermoregulatory responses of brown adipose tissue in a mouse model of diet-induced obesity. FASEB J 2014. [Abstract] EPub

Puente BN, Kimura W, Muralidhar SA, Moon J, Amatruda JF, Phelps KL, Grinsfelder D, Rothermel BA, Chen R, Garcia JA, Santos CX, Thet S, Mori E, Kinter MT, Rindler PM, Zacchigna S, Mukherjee S, Chen DJ, Mahmoud AI, Giacca M, Rabinovitch PS, Aroumougame A, Shah AM, Szweda LI, Sadek HA. The Oxygen-Rich Postnatal Environment Induces Cardiomyocyte Cell-Cycle Arrest through DNA Damage Response. Cell 157:565-579, 2014. [Abstract]

Allen BG, Bhatia SK, Buatti JM, Brandt KE, Lindholm KE, Button AM, Szweda LI, Smith BJ, Spitz DR, Fath MA. Ketogenic diets enhance oxidative stress and radio-chemo-therapy responses in lung cancer xenografts. Clin Cancer Res 19:3905-3913, 2013. [Abstract]

Selected Publications
Applegate MA, Humphries KM, Szweda LI. Reversible inhibition of alpha-ketoglutarate dehydrogenase by hydrogen peroxide: glutathionylation and protection of lipoic acid. Biochemistry 47:473-478, 2008. Abstract

Matsuzaki S, Szweda LI. Inhibition of complex I by ca(2+) reduces electron transport activity and the rate of superoxide anion production in cardiac submitochondrial particles. Biochemistry 46:1350-1357, 2007. Abstract

Oktay Y, Dioum E, Matsuzaki S, Ding K, Yan LJ, Haller RG, Szweda LI, Garcia JA. Hypoxia inducible factor 2 alpha regulates expression of the mitochondrial aconitase chaperone protein frataxin. J Biol Chem 282:11750-6, 2007. Abstract

Bulteau AL, Lundberg KC, Ikeda-Saito M, Isaya G, Szweda LI.  Reversible redox-dependent modulation of mitochondrial aconitase and proteolytic activity during in vivo cardiac ischemia/reperfusion. Proc Natl Acad Sci U S A 102:5987-5991, 2005. Abstract

Churchill EN, Murriel CL, Chen CH, Mochly-Rosen D, Szweda LI.  Reperfusion-induced translocation of deltaPKC to cardiac mitochondria prevents pyruvate dehydrogenase reactivation. Circ Res 97:78-85, 2005. Abstract

Bulteau AL, O'Neill HA, Kennedy MC, Ikeda-Saito M, Isaya G, Szweda LI.  Frataxin acts as an iron chaperone protein to modulate mitochondrial aconitase activity. Science 305:242-245, 2004. Abstract

View all Publications in PubMed

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

Phone: (405) 271-7582
Fax: (405) 271-1437
E-mail: Luke-Szweda@omrf.org

Melinda West
Senior Research Assistant

Caroline Kinter
Research Assistant

Alex Weddle
Research Technician

Clair Crewe
Graduate Student

Jolyn Fernandes
Graduate Student

Jeannie Evans
Administrative Assistant IV

Bailee Macom
Laboratory Assistant