Tracy Deem, Ph.D

Research Interests:

According to the American Heart Association (AHA), cardiovascular disease (CVD) affects men, women, and children independent of ethnicity.  In addition, atherosclerosis is the leading cause of death in the western world.  Atherosclerosis is a chronic inflammatory disease leading to plaque formation in the arterial intima.  This plaque can rupture producing a clot that can prevent blood flow to the heart or brain resulting in a heart attack or stroke, respectively.  Even though atherosclerosis is a major concern for the western world, the current treatments available cannot prevent the disease.  Therefore, better understanding of the early inflammatory stages of atherosclerosis will likely lead to better treatments for prevention.  Atherosclerosis begins with monocyte migration into the artery wall, where they differentiate into macrophages, take up lipid, and form foam cells and fatty streaks.  These macrophages secrete proinflammatory mediators that increase monocyte recruitment into the artery, thus perpetuating disease.  Recently, it has been demonstrated that murine monocytes, like human monocytes, are a heterogeneous population that have diverse immunological functions.  Similar to other leukocytes such as T cells, recent data suggest that various monocyte subsets are either pro- or anti-inflammatory.  Therefore, depending on the subset of monocyte recruited into the tissue, there could be a shift in normal tissue homeostasis resulting in disease.  Consequently, identification of proatherogenic monocyte subsets and their recruitment to and differentiation in the artery wall may provide valuable insights for disease prevention.

Geissman et al. (2003) have demonstrated that there are at least two subsets of monocytes in mice. They named these subsets inflammatory and resident monocytes based on recruitment patterns into tissue.  The inflammatory monocyte subset migrates into the peritoneum of thioglycollate-treated mice, whereas, the resident monocytes are found in tissues of non-treated mice.  These subsets differ in their expression of adhesion molecules and chemokine receptors.  The inflammatory monocyte subset are CX3CR1dimCCR2+CD62L+, whereas, the resident subset is CX3CR1brightiCCR2-CD62L-.  Further analysis of these subsets by Sunderkotter et al. (2004) demonstrated that the inflammatory monocyte subset is released from the bone marrow and matures into the resident monocyte subset in the circulation.  In acute inflammation such as peritonitis and Listeria monocytogenes infection, the more immature inflammatory subset gets rapidly released from the bone marrow and migrates into inflamed tissue.  However, in atherosclerosis, a chronic inflammatory condition, it is not known which subset is recruited into the tissue. Therefore, the focus of my research is to identify the monocyte subset required for disease.

tld5h@virginia.edu