Radiology Personnel

David Marcinek, Ph.D.

Professor

Research

Biography

David Marcinek received his Ph.D. from Stanford University studying muscle metabolism in endothermic and ectothermic fish species. He came to the UW to work with Kevin Conley as a postdoctoral fellow where they developed NMR and optical spectroscopy tools to study the effects of age on skeletal muscle energetics. Since becoming faculty in the Department of Radiology he has been focused on the interaction between mitochondrial oxidative stress and energy metabolism in health and disease.

Research Interests

Mitochondria play a key role in integrating cellular energetics and the control of cell survival. As a result they are a critical element in aging and many degenerative diseases. We believe that an integrated study of mitochondrial energetics in the living organism is required for a mechanistic understanding of the role mitochondria play in degenerative disease. To that end, we have developed novel methods to directly measure mitochondrial function in vivo. Optical and magnetic resonance spectroscopies provide independent measures of oxygen and ATP fluxes in the intact animal. By independently measuring these fluxes we determine several parameters of mitochondrial energetics in skeletal muscle, including the coupling of ATP production to oxygen consumption. We have found that mitochondria in mouse skeletal muscle become less efficient with age, which results in a reduction in the ATP produced per oxygen consumed. This reduced efficiency can lead to an energetic stress on the cell and may impact cell survival. We combine these novel in vivo tools with detailed biochemical analyses of isolated mitochondria and permeabilized muscle fibers. By combining these approaches we are able to integrate the physiological relevance of our in vivo approach with the mechanistic detail available from ex vivo assays.

The focus of our current research is:

1) identifying the role of in vivo mitochondrial dysfunction and loss of energy homeostasis in pathophysiology of aging and disease,

2) the role of mitochondrial toxicity in the pathology associated with multiple xenobiotic compounds such as chemotherapeutic agents, environmental toxins and other drugs.

Education

1989-1993 B.A. – Biology, Kalamazoo College, Kalamazoo, MI

1993-2000 Ph.D. – Physiology, Stanford University, Stanford, CA

2000-2005 Postdoctoral Fellow, University of Washington, Seattle, WA

Recent Publications (via Semantic Scholar)



Mitochondrial Targeted Interventions for Aging.
Sophia Z Liu, Y. Chiao, Peter S Rabinovitch, et al. - Published 2023 - COLD SPRING HARBOR PERSPECTIVES IN MEDICINE

Elamipretide Improves ADP Sensitivity in Aged Mitochondria by Increasing Uptake through the Adenine Nucleotide Translocator (ANT)
Gavin A. Pharaoh, Varun Kamat, Sricharan Kannan, et al. - Published 2023 - BIORXIV

The Study of Muscle, Mobility and Aging (SOMMA). A Unique Cohort Study about the Cellular Biology of Aging and Age-related Loss of Mobility.
Steve Cummings, A. Newman, Paul M Coen, et al. - Published 2023 - THE JOURNALS OF GERONTOLOGY. SERIES A, BIOLOGICAL SCIENCES AND MEDICAL SCIENCES

ATP and NAD+ Deficiency in Parkinson’s Disease
Laurie K Mischley, E. Shankland, Sophia Z. Liu, et al. - Published 2023 - NUTRIENTS

From Mitochondria to Cells to Humans: Targeting Bioenergetics in Aging and Disease.
Brandon J. Berry, Gavin A. Pharaoh, D. Marcinek - Published 2023 - INTERNATIONAL JOURNAL OF BIOCHEMISTRY AND CELL BIOLOGY

Skeletal muscle mitochondrial interactome remodeling is linked to functional decline in aged female mice
A. Bakhtina, Gavin A. Pharaoh, Matthew D. Campbell, et al. - Published 2023 - NATURE AGING

Age and Sex as Determinants of Acute Domoic Acid Toxicity in a Mouse Model
Alicia M Hendrix, K. Lefebvre, Emily K Bowers, et al. - Published 2023 - TOXINS

Randomized crossover clinical trial of coenzyme Q10 and nicotinamide riboside in chronic kidney disease
Armin Ahmadi, G. Begue, Ana P. Valencia, et al. - Published 2023 - JCI INSIGHT

T-cell mitochondria exhibit a functional decline with obesity that is aggravated with weight loss
Ana P. Valencia, S. Melhorn, E. Schur, et al. - Published 2023 - PHYSIOLOGY

A novel mitochondrial complex I ROS inhibitor partially improves muscle regeneration in adult but not old mice
Gavin A. Pharaoh, Ethan L. Ostrom, R. Stuppard, et al. - Published 2023 - REDOX BIOLOGY