Single cell RNA-sequencing from patient samples reveals discrete cell type clustering based on transcriptional activity. Endothelial cells can be identified and compared between critically ill children and those undergoing elective procedures. These comparisons provide unique insight into the blood vessel response to critical illness.
Confocal microscopy of capillary endothelial monolayers treated with patient sera. Treatment results in re-organization of the tight junction molecules claudin-5 and adherens junction protein VE-cadherin (CD144). Smooth junctional staining of claudin-5 is a hallmark of the capillary vascular segment.
Single cell RNA-sequencing from bronchio-alveolar lavagesamples from critically ill children with COVID19. During the pandemic our laboratory made significant contributions to our understanding of viral induced lung injury.
Analysis of trans-endothelial electrical resistance (TEER) across endothelial cell monolayers of time. TEER provides a quantitative, real-time, non-invasive and label free measure of endothelial barrier function. We routinely employ TEER measurements in our investigationsof mechanisms of capillary leak.
Electron microscopy of cultured endothelial cellmonolayers reveals interdigitation at cell boarders with multiple tight junctions. Multiple overlapping cell processes (Top) are characteristic of stable junctions. Retracting cells, such as those stimulated with pro-inflammatory cytokines, exhibit less overlap.
Our passion is to understand blood vessel dysfunction in the setting of critical illness. Blood vessels, and the endothelial cells that line them, extend to within micron of all the cells in the human body. Blood vessels regulate blood volume, flow and fluidity as well as immune and platelet activation. To understand how these processes break down in the setting of critical illness we must understand the fundamental biology of endothelial cells and care for the sickest patients.