Sarah L. J. Michel, PhD, dean and professor of pharmaceutical sciences at the University of Maryland School of Pharmacy (UMSOP), has been awarded a $2.1 million Maximizing Investigators’ Research Award (MIRA) from the National Institutes of Health (NIH) to investigate how hydrogen sulfide (H₂S) regulates zinc finger proteins and gene expression.

The MIRA, awarded by the National Institute of General Medical Sciences (NIGMS), provides long-term support for an investigator’s overall research program rather than a single, narrowly defined project. This approach gives researchers greater flexibility to pursue promising new scientific directions as their work evolves.

Zinc finger proteins are the most abundant class of zinc-containing proteins in eukaryotic cells and play essential roles in regulating gene expression, the process by which cells use the information in genes to make proteins that control how cells function. Zinc finger proteins use zinc ions to form compact, three-dimensional structures that allow them to bind to DNA or RNA. Michel’s laboratory has discovered a new way in which H₂S, a naturally occurring signaling molecule in the body, can alter the function of these proteins.

H₂S modifies cysteine residues in proteins through a process called persulfidation. Michel and her team have found that persulfidation can dramatically alter zinc finger protein function, including disrupting their ability to bind DNA or RNA and potentially changing the genes they regulate.

“We have uncovered what we think is a fundamentally new way of thinking about how zinc finger proteins are regulated,” said Michel. “These proteins make up approximately eight percent of all eukaryotic proteins, so understanding how hydrogen sulfide modifies their function could have broad implications for gene regulation and human health.”

With support from the MIRA, Michel’s research team will focus on three central questions: Which types of zinc finger proteins are persulfidated? How does zinc finger persulfidation alter gene expression? And what molecular triggers turn H₂S signaling on?

To answer these questions, the researchers will use a “molecules-to-proteomics” approach that combines biochemical and bioanalytical studies with cell-based experiments and persulfide-specific proteomics. The team will identify specific sites of persulfidation and investigate how those modifications affect protein function, while using proteomics to determine which classes of zinc finger proteins undergo persulfidation and what cellular signals regulate the process.

“The MIRA is particularly exciting because it gives us the flexibility to follow the science,” said Michel. “We can investigate the fundamental chemistry of these proteins and then move into cells and across the proteome to understand how this mechanism affects gene regulation more broadly.”

H₂S signaling has been linked to physiological and pathological processes relevant to cardiovascular health, metabolism, cancer, and neurological disorders. By determining how H₂S can reprogram zinc finger protein function, Michel’s research could provide new insight into an important and largely unexplored mechanism of cellular regulation.

“Hydrogen sulfide is a fascinating signaling molecule in biology and in this exciting new area of research, Dean Michel is exploring how it regulates zinc finger proteins,” said Mark T. Gladwin, MD, dean of the University of Maryland School of Medicine.

Michel is an internationally recognized leader in the field of metals in medicine. Her work has been funded by the NIH, the National Science Foundation, and U.S. Army Research labs for investigating the roles that metals play in the regulation of chronic inflammation, cancer, and neurodegenerative diseases. She has also been active in clinical research through U.S. Food and Drug Administration (FDA) grants and has been closely involved with the Maryland Center of Excellence in Regulatory Science and Innovation. In 2025, she was named the Maryland Chemist of the Year by the state chapter of the American Chemical Society.

“Persulfidation of zinc finger proteins is a fundamentally important, yet understudied area of research with significant implications for our understanding of gene regulation, said Hongbing Wang, PhD, professor and interim chair of the Department of Pharmaceutical Sciences and a University of Maryland, Baltimore Distinguished University Professor. “Dr. Michel has made substantial contributions to this field and is well positioned to continue advancing our knowledge in this important area.”