My research passion to better understand how blood vessels respond to critical illness. I investigate the translational and basic science of endothelial cell function and dysfunction in culture as well as how these changes affect critically ill. My research starts at the bedside and continues in laboratory. Ultimately, I hope to may a discovery to help reduce blood vessel dysfunction that will help critically ill children.
My three professional passions are providing excellent patient care, educating trainees, and conducting clinically impactful vascular research. In the PICU, I strive to provide compassionate, high quality and timely care to all my patients. Teaching trainees is also a top priority, and I routinely give many formal lectures, short talks as well as create curriculums and educational materials. I invest time and energy in my lectures to make sure they are clinically relevant and are appropriate for all levels of trainees. Finally, I am passionate about my research, where I investigate blood vessel dysfunction and its consequences in critically ill children, with a keen focus on permeability changes. Ultimately, I would like to develop new therapies to target the blood vessels that improve the lives of critically ill children.
My laboratory focuses on several interrelated avenues of research. First, I investigate how EC junctional molecules are regulated in the setting of inflammation. These investigations occur in culture models of capillary endothelium and focus on small GTPases and their regulators, GAPs and GEFs, regulate permeability of EC monolayers and re-organization of tight junction molecules. I demonstrated the importance of the regulation of the small GTPase RhoB in a pediatric patient with systemic capillary leak syndrome caused by a single gene mutation in a GAP with previously unknown function, p190BRhoGAP. We are focused on understanding the GAP and GEF regulation of RhoB have branched to investigate other small GTPases in the Rap family.
A second major avenue of research is on the clinical mechanisms and consequences of EC dysfunction in critically ill children. I place great emphasis on maintaining direct clinical relevance in my research projects and have focused my efforts on human samples. To this end, I established a prospective study investigating the single-cell transcriptomic changes of EC isolated from critically ill children compared to healthy children. This project has identified a new small molecule mediators of blood vessel function in critical illness. This line of research has lead to new investigations into how blood vessels break down and medications that may restore barrier function.
Another focus of my lab is investigating consequences of vascular dyfunction in critically ill children, namely pulmonary capillary dysfunction in pediatric acute lung injury. We leverage cutting edge multi-omic techniques on patient samples to survey immune cells isolated from the lungs of critically ill children with acute lung injury. Finally, I am active in Yale’s own Pediatric Genomic Discovery Program (PGDP) and am able to rapidly investigate the effects of clinically impactful gene mutations on vascular function.
Blood Vessels; Capillary Permeability; Cardiovascular System; Endothelium; Endothelium, Vascular; Pediatrics; Intensive Care Units, Pediatric; Sepsis; Capillary Leak Syndrome; Genomics; Severe Acute Respiratory Syndrome; Acute Lung Injury; Microvessels; Translational Research, Biomedical; COVID-19