Ellen Weinberg Ph.D.
Office: 650 Albany St., X-616
Dr. Weinberg’s laboratory is interested in the role of inflammation in cardiovascular diseases including hypertrophy and heart failure. They have identified an interleukin-1 receptor family member (IL1RL1; ST2) by genome-wide transcriptional profiling as a gene highly induced in cardiac myocytes. ST2 encodes a soluble receptor as well as a membrane-anchored receptor (ST2L) that are both regulated at the level of mRNA by alternative promoter usage (rather than by cleavage and release). Her laboratory has demonstrated that ST2 serum levels were increased in the serum of patients with myocardial infarction and heart failure. This also correlated with clinical parameters, and importantly, provided prognostic information. As a result of this work, the use of ST2 as a cardiovascular biomarker is emerging as standard practice in clinical laboratories across the United States. A second focus of research is the function of the recently identified ST2L receptor ligand, IL-33. As an extra-cellular ligand, recombinant IL-33 drove the production of Th2-type cytokines and caused eosinophilic inflammatory pulmonary disease in a mouse model. However, IL-33 was first identified as a nuclear factor in inflamed high endothelial venules that possesses transcriptional repressor properties in endothelial cells in vitro assays. Thus, IL-33 is a “dual-function cytokine” similar to other interleukin-1 family members. The nuclear, intracellular function of IL-33 is the primary research focus. Using siRNA to IL-33, they demonstrated that endogenous IL-33 in endothelial cells may repress NF-kB regulated transcription, a function that is separate from its role as an extra-cellular ligand of the ST2 receptor. Interestingly, they recently demonstrated that mRNA levels of ST2L and IL-33 are highly correlated in human leukocytes, suggesting co-regulation in these cells. They are currently studying the transcriptional regulation of the ST2 gene, possibly by nuclear IL-33, at the level of chromatin remodeling and accessibility. The goal is to understand mechanisms of regulation of these two genes in a cell type-specific manner as they relate to inflammatory disease processes, including not only cardiovascular diseases, but also vasculitis, sepsis, and pulmonary diseases.