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Pharmacology & Chemical Biology Seminar Series
9/29/2022 - 12:00 PM-1:00 PM
“The cell biology of heme trafficking and a new role for NO in its regulation”

Dennis Stuehr, PhD 
Professor, Cleveland Clinic, Lerner Research Institute

Heme is an important form of biologically active iron in cells. Heme levels participate in cell signaling and gene expression, and when bound in proteins enables various electron transfer, small molecule transport, and catalytic functions.  Because the final steps of heme biosynthesis take place inside the mitochondria and free heme is toxic, mechanisms exist to carefully control its level and to enable its transport and delivery to the many hemeproteins that mature and function outside of the mitochondria.  Moreover, evidence is emerging to suggest that differences in heme allocation and homeostasis influence important aspects of cancer progression and inflammation. Our lab is identifying the proteins that help to deliver heme and insert it into proteins, and uncovering the mechanisms that regulate these processes. The talk will highlight key roles for GAPDH and chaperone hsp90 in driving heme delivery and insertion into various targets including sGC, hemoglobin, myoglobin, NOS, and Trp dioxygenases, and will show how biologic NO can either up- or down-regulate these processes, depending on its flux. Overall, these findings may help explain how heme homeostasis is achieved in cells and can become dysregulated in disease.

Thomas E. Starzl Biomedical Science Tower
1395 Conference Room
203 Lothrop St
Pittsburgh, PA 15213
Melanie Hoffner

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