Richard A. Zager

Appointments and Affiliations

 
 
Fred Hutchinson Cancer Research Center
Clinical Research Division
Nephrology
Head
University of Washington
School of Medicine
Medicine
Nephrology
Professor, Appointed: 1988
Professional Headshot of Richard A. Zager

Mailing Address

Fred Hutchinson Cancer Research Center
1100 Fairview Avenue N.
P.O. Box 19024
D2-190
Seattle, Washington 98109-1024
United States

Contact

Phone: (206) 667-6222
Fax: (206) 667-6519
dzager@fhcrc.org

Degrees

M.D., Northwestern University, 1969.

Research Interests

The primary focus of the renal program is the study of how the kidney adapts to toxic and ischemic insults, resulting in acquired resistance to further attack. Research conducted over the last 2 years has indicated that sublethal injury evokes adaptational changes in the plasma membrane which render the membrane resistant to oxidative and phospholipase mediated damage. While several echanisms can contribute to this state, the dominant one identified as of this time is an upregulation of membrane cholesterol content. This leads to a decrease in membrane fluidity, which, by itself is cytoprotective. In addition, there is a injury-evoked perturbation of cholesterol cycling within the cell, culminating in the excess production of cholesterol esters. Thelatter may then be directly cytoprotective by positively influencing mitochondrial energy production and decreasing oxygen free radical generation. The laboratory is now addressing how clinically relevant agents, administered routinely to bone marrow transplant patients, impact these pathways. One key factor is cyclosporine A which has pronounced effects on the above noted events. As one example, cyclosporine inhibits normal cholesterol homeostasis, thereby altering cellular responses to attack.

A second and unrelated focus of this laboratory is the study of vitamin D metabolism, its response to systemic cytokines, and how these factors evoke hypocalcemia in critically ill patients. These clinical studies are being undertaken in both BMT and non BMT patients, the latter hospitalized in ICUs in UW hospitals. This group has demonstrated that hypocalcemia occurs in as many as 90% ICU patients, and is equal to APACHE II scores in predicting adverse patient outcomes. These studies also have a basic research component as key hypotheses derived from the clinical data are tested in a laboratory setting.

Recent Publications

2014
Zager, RA, Johnson ACM, Becker K.  2014.  Renal Cortical Pyruvate Depletion during AKI.. Journal of the American Society of Nephrology : JASN. Abstract
2013
Zager, RA, Johnson AC, Becker K.  2013.  Post-ischemic azotemia as a partial 'brake', slowing progressive kidney disease.. Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association. 28(6):1455-62. Abstract
Zager, RA.  2013.  'Biologic memory' in response to acute kidney injury: cytoresistance, toll-like receptor hyper-responsiveness and the onset of progressive renal disease.. Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association. 28(8):1985-93. Abstract
2011
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2007