William C. Orr, Ph.D.
Professor and Department Chair
Ph.D. Wayne State University
Postdoc Harvard University
Lab: DLSB 315
Lab: DLSB 317
Oxidative Stress and Aging/Redox regulation
My principle research focus lies in the use of transgenic and genetic models to identify mechanisms that affect aging, with emphasis on the impact of redox state regulation. Currently there are two on-going projects in our laboratory.
The first of these is designed to elucidate the potential role of peroxiredoxins on oxidative stress, aging and immunity in Drosophila. The peroxiredoxins represent a group of recently identified components of the antioxidative network, which reduce H2O2 and organic peroxides, using thioredoxin as an electron source, and also serve as redox sensors in signal transduction pathways. Analysis of this gene family has allowed us to reveal elements of both antioxidant function and redox regulation related to longevity and innate immunity.
In a second study, we are specifically testing the hypothesis that Peroxiredoxin 6 (Prx 6) contributes to the progression of the Alzheimer’s phenotype. Peroxiredoxin 6 (Prx6), is known to possess antioxidant function through its peroxidase activity (PRX) and to regulate inflammation through its phospholipase activity (PLA). It is expressed at high levels in Alzheimer’s patients and, when overexpressed in a mouse AD model, actually exacerbates the AD phenotype. We are currently using a Drosophila model of Alzheimer’s to test the hypothesis that it is the phospholipase activity in the Prx6 gene that elicits a chronic state of inflammation and contributes to the Alzheimer’s phenotype.
Radyuk, S.N., Orr, W.C. (2018) The multi-faceted impact of peroxiredoxins on aging and disease. Antioxid. Redox Signal. In Press
Odonokoz, O., Nakatsuka, K., Klichko, V.I., Nguyen, J., Calderon-Solis, L., Ostling, K., Badinloo, M., Orr, W.C., Radyuk, S.N. (2017) Mitochondrial peroxiredoxins are essential in regulating the relationship between Drosophila immunity and aging. Biochim Biophys Acta 1863(1), 68-80
Orr, W.C. (2016) Tightening the connection between transposable element mobilization and aging. Proc. Natl. Acad. Sci. 113(4), 11069-70.
Klichko, V.I., Orr, W.C., Radyuk, S.N. (2016) The role of peroxiredoxin 4 in inflammatory response and aging. Biochim Biophys Acta 1862(2),265-273
Orr, W.C., Radyuk, S.N. and Sohal, R.S. (2013) Involvement of redox state in the Aging of Drosophila melanogaster. Antioxid. Redox Signal. 19, 788-803.
Radyuk, S.N., Klichko, V.I., Michalak, K. and Orr, W.C. (2013) The effect of peroxiredoxin 4 on fly physiology is a complex interplay of antioxidant and signaling functions. FASEB J, 27, 1426-1438.
Radyuk, S.N., Gambini, J., Borras, C., García, E.S., Klichko, V.I., Viña, J. and Orr, W.C. (2012) Age-dependent changes in the transcription profile of long-lived Drosophila over-expressing glutamate cysteine ligase. Mech. Ageing Dev. 133(6), 401-413.