Glucocorticoids in short- and long-term critical illness outcomes

Enter the text here that is the new abstract information for your application. This section must be no longer than 30 lines of text. Because of the high mortality, morbidity, and health care costs associated with critical illness, identifying biological mechanisms that can be targeted to improve critical illness outcomes is an important public health priority. Glucocorticoid treatment has been frequently studied in critically ill populations and can improve short-term survival as well as long-term mental health outcomes. Full realization of the therapeutic potential of glucocorticoids in critical illness is hampered by gaps in our understanding of its mechanisms of action and by glucocorticoid resistance, which limits its efficacy. Our future research program will focus on the theme of glucocorticoid mechanisms relevant to critical illness, with three main objectives. First, our prior work led us to hypothesize that glucocorticoids improve mental health outcomes by enhancing factual memories from the ICU. We will test this hypothesis in a population of sepsis survivors from our hospital. Second, we propose a novel hypothesis about the importance of brainstem glucocorticoid signaling in the maintenance of cardiovascular and immune homeostasis. We will test the role of glucocorticoid receptors in this specific brainstem area in the response to acute hypotensive and inflammatory challenges using the tools and skills that we have acquired for neural circuit interrogation. Finally, we propose to test a novel strategy to improve peripheral and central glucocorticoid sensitivity in collaboration with a new industry partner. Over the past five years I have positioned myself as a multidisciplinary leader across critical care, endocrinology, and neuroscience. My experience running a translational research program at this interface will lead to the identification of specific, targetable mechanisms to improve critical illness outcomes.