Skeletal muscle heme oxygenase-1 [HO-1] activity regulates aerobic capacity

Physical exercise is enormously important for quality of life, and a cellular hallmark of exercise is the release of free heme following muscle micro trauma. Heme is an important signaling molecule but can be toxic at high doses. Two enzymes are responsible for heme degradation, Hpx, and HO-1. Hpx is an enzyme that scavenges free heme and transports it into cells where it is degraded by the enzyme HO-1. The products of heme degradation by HO-1, among which are carbon monoxide, are highly protective and anti inflammatory. In this paper produced by members of my lab, the hypothesis that heme metabolism is critical in skeletal muscle cell recovery and maintenance of function after aerobic exercise was tested. We show that in the absence of Hpx, the enzyme responsible for scavenging free heme, both untrained and trained mice exhibit no muscle deficits. In contrast, mice lacking HO-1 selectively in skeletal muscle fibers show dramatic structural and functional remodeling toward a fast and more fatigue-prone phenotype. We discovered that loss of HO-1 within muscle fibers impaired the benefits of aerobic exercise training (TR) and altered the muscle phenotype within weeks of deletion, driven largely by changes in metabolism and mitochondrial bioenergetics. Collectively, this study provides insights into the role of heme flux, and HO-1 activity, as an essential pathway necessary for developing and maintaining exercise capacity and muscle physiology.

Neutrophil Extracellular Traps (NETS)

Neutrophils are immune cells that are a subset of the innate immune system and the main cells that I focus on. Evolution has gifted them a variety of ways in which to neutralize foreign bodies, from bombardment with damaging reactive oxygen species to microbicidal proteins. Personally, one of the most interesting facets of neutrophil killing activity are NETS. These are (literal) nets cast out by neutrophils upon sensing foreign bodies, comprised largely of DNA and concentrated with proteins. The NETS function by catching bacteria and trapping them in the nucleic acid fibers where they are then subjected to several microbicidal proteins, almost like a spider web. Besides providing additional antimicrobial activity outside of phagocytosis, NETS function to prevent further spread of pathogens, and may even serve to prevent host damage by keeping harsh enzymes close to the cell and not diffusing into host tissue.

Evasion of Neutrophil Killing by Staphylococcus aureus

A lot of my research is focused on immunology and the ways that our immune system acts and eliminates threats under certain experimental conditions. It's always necessary to realize however that pathogens have evolved highly complex ways to counter our immune system, and can inhibit everything from neutrophil recognition and phagocytosis to killing. There's always another side to the story.

Carbon Monoxide as a Therapeutic