Our research laboratory is interested in understanding the molecular mechanisms required for the regulation of blood vessel development and vascular inflammation. One of the main approaches used in the laboratory to understanding these biological processes is to identify the transcription factors that act as master switches for these processes. Our particular focus has been on the role of one family of transcription factors known as the Ets transcription factor family. Several vascular-specific genes have conserved binding sites for the Ets factors in their genomic regulatory regions. We have identified the specific members of the Ets factor family that regulate the vascular specific tyrosine kinase genes Tie1 and Tie2. These Ets factors are enriched in developing blood vessels during embryogenesis. One of the major research objectives in our laboratory is to identify the role for these transcription factors in regulating blood vessel development as well as endothelial differentiation and endothelial function. Because many of the events that occur during vascular development in the developing embryo are recapitulated during angiogenesis, a process of new blood vessel development that can occur in a variety of diseases, we believe that the same factors may also regulate angiogenesis. Some of the disease in which angiogenesis may be harmful include tumor angiogenesis, or the angiogenesis associated with diabetic retinopathy. Angiogenesis can be beneficial in such disease states as coronary heart disease. The identification of the critical transcription factors required for vascular development will promote the development of novel regulators of angiogenesis.
Another area of interest within the laboratory is vascular inflammation. Vascular inflammation is associated with a number of diseases including the most common disease in the United States, coronary heart disease. Other diseases associated with inflammation of blood vessels include bacterial sepsis, a process called restenosis, which often occurs after an angioplasty which is used to treat patients with blockages in the blood vessels that supply the heart. We have identified a transcription factor which is induced very early on in the process of vascular inflammation, and which may help serve as one of the master switches for mediating this process. One of the targets for this factor is an enzyme called nitric oxide synthase, which produces nitric oxide, and important regulator of blood vessel tone and normal function.