Research Interests

A major focus of the laboratory is on understanding the roles that immune cells have in the pathophysiology of disease. In my lab, we use a combination of pharmacological and genetic techniques to probe the cellular signaling mechanisms that regulate immune cells during the disease process. We are particularly interested in identifying ways in which immune cell phenotypes can be regulated pharmacologically to protect against disease. Since inflammation and immune cell responses are involved in the pathophysiology of many diseases, our research is applicable to various diseases and we employ the use of several different animal models of disease. We currently have several projects available for graduate students and post-doctoral fellows.

Stroke:

We have identified the myeloid mineralocorticoid receptor as a regulator of macrophage polarization and have found myeloid MR to be an important pharmacological target during a model of ischemic stroke. We have shown that genetic deletion of MR in myeloid cells is highly protective in an ischemia-reperfusion model of ischemic stroke. (Frieler R.A. et al., Stroke 2010)

We are now focused on understanding the mechanisms by which MR activation in myeloid cells contributes to stroke pathophysiology. Along these lines, we are also working to identify and define other important signaling pathways that alter myeloid cell phenotype during stroke. Some of the other myeloid cell modifiers that we are interested in include PPAR-gamma and IL-4. In addition, we also use a variety of cell type depletion models and specific targeting strategies to delineate the importance of specific cell types and the cellular targets for specific signaling pathways.

Potential Projects:

1) Modulation of immune cell responses to protect against stroke.

2) Delineation of microglia responses during stroke

3) Mechanisms of MR-mediated regulation of myeloid phenotype during stroke

4) Regulation of myeloid phenotype by IL-4 and PPAR-gamma during during stroke

Traumatic Brain Injury:

Leukocyte recruitment and inflammation occurs in response to traumatic brain injury (TBI), and we have similar interests in identifying important mechanism of pharmacological control of immune cell phenotypes during brain injury. We use a controlled cortical impact model of TBI to study the role of specific immune cell types and signaling pathways during the inflammatory response to brain injury.

Cardiac Injury:

Mineralocorticoid receptor antagonists have protective effects in humans in the treatment of heart failure and post-myocardial infarction remodeling. We have shown in an animal model of cardiac inflammation, hypertrophy, and fibrosis, that myeloid cells are important pharmacological targets for this class of drugs.