Sarah L.J. Michel, PhD Dean and Professor of Pharmaceutical Sciences, University of Maryland School of Pharmacy

The Department of Chemistry Presents: Sarah L.J. Michel, PhD, Dean and Professor of Pharmaceutical Sciences,University of Maryland School of Pharmacy

Zinc finger proteins (ZFs) are a large class of proteins that use zinc as structural cofactors. ZFs have critically important roles in modulating transcription and translation. ZF proteins contain one or more domains with four conserved cysteine and/or histidine residues that serve as ligands for zinc. Upon zinc binding, ZFs fold and function. The accepted dogma for ZF proteins is that they are structural sites; however, there is emerging evidence for reactivity of ZFs with endogenous signaling molecules including H₂S. H₂S is a gasotransmitter that plays key roles in biology ranging from neuromodulation to regulation of inflammation. The molecular targets of H₂S include heme and non-heme iron proteins, reactive oxygen-, sulfur-, and nitrogen species, and cysteine residues on proteins. The interaction of H₂S with protein cysteine residues (P-SH) involves a post-translational modification (PTM) called persulfidation - the addition of sulfur to protein cysteine residues (P-SH à P-SSH). We have discovered that ZF proteins are targets of H₂S in cells, using a persulfide specific chemoselective proteomics approach. The mechanism by which ZFs are persulfidated has been evaluated in several ZF proteins, and we have discovered a common mechanism that involves Zn serving as a conduit to bring H₂S and O₂ together for electron transfer. These results as well as our efforts to understand how the pro-inflammatory response triggers ZF persulfidation will be presented.

BIO

Sarah L. J. Michel is the Dean and Professor of Pharmaceutical Sciences at the University of Maryland School of Pharmacy. Her research focusses on metallobiochemistry, and she was trained in inorganic chemistry at Northwestern (PhD, Chemistry with Brian Hoffman) and in biophysics and biophysical chemistry at the Johns Hopkins University School of Medicine (NIH postdoctoral fellow with Jeremy Berg). Her research program at UMB spans basic and translational science, and includes a focus on the role of H₂S and toxic metals in zinc finger protein function and on the development of new approaches to understand how iron nanomedicines deliver iron to patients with iron deficiency anemia for which she recently completed a multi-PI FDA funded clinical trial.