METABOLOMICS AND PATHOBIOLOGY

We have devoted significant attention in recent years to the role of sphingolipid metabolism in sickle red blood cells. We have recently identified a novel mechanism of feed-forward inflammatory signaling in SCD whereby sickled RBC membrane strain increases the activity of sphingomyelinase (SMase), which contributes to membrane lipid composition and budding of cellular vesicles. This dysregulation of sphingolipid metabolism leads to the aberrant production and release of cell-derived microparticles (SS MVs). MVs have been described as transcellular delivery vehicles that can transfer receptors, adhesion molecules, kinases, and lipids between cells. We are also investigating a potential pathogenic role of SS MVs in bone and joint disorders including osteonecrosis of the femoral head (ONFH). Read More

SMART BIOMATERIALS

An additional interest is the development of “immunologically smart” biomaterials that can tune the regenerative potential of subpopulations of leukocytes to the needs defined by the injury microenvironment. Our goal is to harness the phenotypic complexity and the division of labor among innate immune cell subsets to amplify endogenous mechanisms of tissue repair. In one recent example, we have shown that diverting circulating non-classical monocytes to injury sites using extracellular matrix (ECM)-derived hydrogels promotes healing and inflammation resolution in musculoskeletal injuries. Read More

ENDOGENOUS TISSUE ENGINEERING

Our interest is to understand the microenvironmental factors that govern healing outcomes in musculoskeletal tissues and skin in order to harness endogenous mechanisms of repair. Efficient wound healing requires the angiogenic and fibrogenic activity of macrophages, which are derived at least in part from circulating monocytes that undergo differentiation post-extravasation. We focus specifically on unlocking the therapeutic potential of pro-regenerative monocyte subsets and their progeny. Learn More