Dr. Stark's laboratory research focuses on the mechanisms through which acute inflammatory responses alter vascular function and contribute to critical illness. Further, he is interested in discovering ways to limit the negative impact inflammation has on the endothelium and associated vascular system.

Previous NIH-funded research investigated how endothelial cells are affected during infection, with specific focus on endothelial nitric oxide synthase (eNOS) dysfunction. Furthermore, Dr. Stark's lab examined how priming of the immune system with a TLR4 agonist, monophosphoryl lipid a (MPLA), altered the pro-inflammatory responses of activated endothelial cells with secondary infectious challenges. They have also examined a group of metabolic regulators of inflammation, known as sirtuins (SIRTs). They found that loss of SIRT1, which occurs during prolonged sepsis and with age, alters the metabolic phenotype of the endothelial cells to where they have a "metabolic shift" away from oxidative phosphorylation, the primary source of energy production, to glycolysis.

Additionally, a translational aspect of the program studies endothelial dysfunction in humans using a technique called laser doppler perfusion monitoring which is coupled to drug iontophoresis. This system allows us to test the function of the vasculature in critically ill patients using drugs that either stimulate the endothelial cells (acetylcholine) or the vascular smooth muscle cells (sodium nitroprusside). They have found in children undergoing either cardiopulmonary bypass for the correction of congenital heart surgery or those who present with sepsis, that endothelial-dependent vascular reactivity is more strongly impaired compared to endothelial-independent mechanisms, suggesting that the vascular dysfunction observed in critically ill children is primarily driven by endothelial dysfunction.

The Stark Lab's long-term goal is to understand the mechanisms of acute vascular dysfunction and find modalities that allow for identification and future treatment. Dr. Stark has been involved in academic research throughout his career and has a passion to answer questions that arise in critically ill patients. He has also been involved in mentoring younger trainees with the hope of inspiring them to think critically and pose new and interesting questions on how to approach critical illness. His lab’s goal is to continue these pursuits by asking clinically-relevant questions, investigating them with trainees in the laboratory and hospital settings, and ultimately, finding answers that can be brought back to patients to help temper the severity of illness and reduce morbidity and mortality in the vulnerable population of pediatric critical illness.

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