My laboratory investigates the role of hydrogen sulfide (H2S) signaling in vascular regulation and metabolism under physiological and pathological conditions (e.g., inflammation, critical illness, myocardial ischemia, colorectal cancer, and
viral infection). H2S has been identified as a crucial gaseous mediator in the mammalian system that regulates and modulates various cellular actions (e.g., cell survival, proliferation, migration, barrier function, and mitochondrial bioenergetics).
My early research studies demonstrated that mitochondrial H2S production is physiologically indispensable in maintaining cellular bioenergetics of mammalian cells via supporting and balancing mitochondrial electron transport and complements
the action of the “classical” Krebs cycle-derived electron donors. We revealed that H2S signaling is impaired in conditions of oxidative stress, such as diabetes, which contributes to vascular complications. Stimulating H2S
production in endothelial cells supports angiogenesis and may serve as a therapy for new vessel formation after ischemic tissue injury. Currently, in my laboratory, we are exploring the role of the H2S-producing enzyme 3-MST in colon cancer-associated
tumor angiogenesis. We aim to specifically block 3-MST function in endothelial cells of the tumor microenvironment to inhibit tumor growth in the colon and distant organs. This project will unveil novel pathogenic roles of the 3-MST/H2S
axis in tumor biology and define the translational relevance of identifying 3-MST as a new target for colorectal cancer therapy. In another project, we investigate how H2S limits colonic mucosal inflammation and stimulates wound repair
and angiogenesis in physiological conditions. More specifically, our recent finding suggests that H2S production in the colonic mucosa is significantly suppressed in patients with ulcerative colitis, initiating colitis-associated carcinogenesis.
If we could specifically repair and stimulate colonic mucosa cells’ H2S production, we could reduce inflammation, promote tissue healing, and prevent colitis-associated carcinogenesis. Lastly, we have also initiated a new line of
research to explore the role of H2S signaling in COVID-19–associated endotheliopathy.
Katalin Modis, PharmD, PhD
Division Co-Chief of Surgical Sciences