The overarching goal of our laboratory is to understand the axis of cytokines, signaling pathways and cellular responses that lead to complications and poor outcomes in the critically ill. Ongoing work in our laboratory is focused on developing interventional strategies that will improve outcomes in patients with pneumonia or anemia.
Pneumonia is one of the most common life threatening complications in the intensive care unit. The outcome of pulmonary infection is determined by a delicate balance between appropriate inflammatory responses orchestrating effective clearance of microbes from the lung and excessive inflammatory responses that can compromise gas exchange and lead to respiratory failure. Our laboratory is currently investigating strategies of modulating the innate immune response against infection to facilitate clearance of pathogenic microbes from the lung.
The anemia of critical illness (ACI) develops in nearly all patients that enter the critical care unit within eight days of admission. ACI is a persistent anemia that is associated with an inappropriately low erythropoietin (EPO) response, poor marrow red cell production and ongoing inflammation. Several inflammatory mediators are thought to suppress erythropoiesis through alterations of normal iron metabolism, erythropoietin production or responsiveness, or erythroid progenitor differentiation and survival, but the mechanisms remain poorly understood. ACI is a primary cause of anemia in the burn patient and a major factor driving the need for transfusion. Transfusions in burn patients are associated with poor outcomes and increased episodes of infection. Our laboratory is working to define the molecular mechanisms responsible for impaired erythropoiesis following burn injury with a goal of developing therapeutic approaches to reduce transfusions.
Potential project for students or fellows:
The student or fellow will be testing a hypothesis that elevated granulocyte colony stimulating factor (G-CSF) and reduced insulin-like growth factor 1 (IGF-1) serum levels associate with increased erythropoietin requirements in patients with end stage renal disease. Responsibilities would include assisting with the collection and processing of human blood samples as well as performing assays to quantify G-CSF and IGF-1 in serum. The student or fellow may also participate in the development of an EPO stimulation assay that will utilize primary erythropoietic cultures derived from human bone marrow cells to assess in vitro EPO resistance by flow cytometry.