Professor Steve Ragsdale

Professor Steve Ragsdale

David Ballou Collegiate Professor

Department of Biological Chemistry

University of Michigan

Abstract

"Heme oxygenase and its Role in Regulating Human Heme Homeostasis and Carbon Monoxide Metabolism"

Heme oxygenases (HO1 and HO2) play critical roles in iron, heme and CO metabolism and signaling in mammalian cells. HOs are the sole heme degrading systems in mammals, as well as the source of CO, an important signaling molecule. I will discuss our recent cellular and biochemical methods to investigate key steps in heme homeostasis and CO signaling involving heme oxygenase and the nuclear receptor Rev-Erb. HO2 and Rev-Erbβ exhibit similarities in their modes of heme and thioldisulfide redox regulation via their heme responsive motifs (HRMs). We recently described novel roles for the HO2 catalytic core in regulating cellular heme bioavailability via heme sequestration, in addition to the known roles of HO1 and HO2 in enzymatic conversion of heme to biliverdin, CO, and free Fe. I will also dis- cuss a heme shuttling mechanism for HO2 involving heme delivery from its cellular chaperone to an intrinsically disordered C-terminal domain and finally to the catalytic core domain, where it is sequestered and/or degraded. I will further describe recent studies of Rev-Erb, where we identified a coupling mechanism that drives conversion of the resting Fe(III) form of heme to the Fe(II)-CO that we feel is relevant for many heme and CO regulated proteins. Our research will help understand HO’s involvement in cellular protection against cardiovascular, renal, and central nervous system pathologies and how heme homeostasis regulates the function and stability of other downstream hemoproteins like Rev-Erbβ, which itself is associated with regulating metabolism, circadian rhythm, and inflammation.

Steve Ragsdale

Stephen W. Ragsdale was born in Rome, Georgia USA in 1952. He received his BS and PhD degrees in Biochemistry from the University of Georgia before joining Harland Wood’s laboratory for a postdoctoral stint at Case Western Reserve University. He was an Assistant Professor at University of Wisconsin-Milwaukee, and then went through the ranks from Associate to Full Professor to George Beadle Professor of Biochemistry at the University of Nebraska. He moved to the University of Michigan in 2007, where he is a Professor in the Department of Biological Chemistry. Much of his research has focused on microbial biochemistry related to bioenergy generation, metalloproteins and the biochemical pathways related to the formation and uptake of greenhouse gases in the earth’s atmosphere. Another major area is studying how redox, gaseous signaling molecules (CO, NO) and heme regulate metabolism in humans. He has published over 230 papers, including reviews and primary publications. He has been active in the various societies and is a Fellow of the American Society of Microbiology and of the American Academy of Arts and Sciences. Other activities include Editorial Board memberships and grant review service on NIH, Department of Energy, and NSF panels. He is very interested in training and science education and a number of his former students, postdoctoral associates are now faculty members in academia, and others are in industry. He teaches courses in sciences as well as in the areas of creative process and practical science topics (ethics, grant writing, seminar presentation). Besides science, he enjoys playing guitar and piano and practicing yoga.

Start date
Thursday, Nov. 3, 2022, 9:45 a.m.
End date
Thursday, Nov. 3, 2022, 11 a.m.
Location

331 Smith Hall

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