Integrated Vascular Biology Laboratory

Dan Berkowitz, M.D., Alfred Habeeb Professor and ChairEnika Nagababu, Ph.D., faculty member and scientist; and Sarav Murugesan, Ph.D., postdoctoral fellow 

The Berkowitz laboratory has been studying the mechanisms contributing to the pathobiology of vascular dysfunction in diseases such as age-related systolic hypertension, atherosclerosis, radiation-induced vascular injury, and pulmonary hypertension. Our integrated vascular biology laboratory has been continuously funded for 15 years by the NIH, as well as the American Heart Association and NASA through the National Space Biomedical Research Institute.

One of the focuses of the laboratory in the past has been the mechanism contributing to vascular stiffness in aging. We identified the upregulation arginase as an important mechanism for endothelial dysfunction in aging. Indeed, the upregulation of arginase leads to a significant decrease in the production of  the vasoprotective gas nitric oxide through competition for the common substrate L-Arginine. Moreover, we have demonstrated that arginase upregulation contributes to the endothelial dysfunction associated with atherosclerosis. 

We have also studied the role of cross-linking enzymes such as transglutaminase and Lysyl Oxidase like Enzyme 2 in the pathobiology of age-related vascular stiffness. We have shown that increases in cross-linking activity of these enzymes contribute to the stiffness and systolic hypertension associated with aging. Recently we have also studied the role of sensory G- protein coupled receptors that appear to mediate diverse functions in extrasensory sites. For example, we showed that the non-visual opsin, melanopsin or opsin 4, mediates vasodilation in both systemic and pulmonary vascular beds.  

Currently the laboratory is focused on studying the molecular mechanisms contributing to pre-eclampsia, a condition characterized by systemic and pulmonary hypertension, endothelial dysfunction, and capillary leak in pregnancy. We have a host of equipment for measuring function in isolated vessels as well as integrated vascular function in vivo. We also have a host of instruments for biochemical assays and molecular techniques. Finally, we are in the process of developing a new technology that will allow for the delivery of inhaled nitric oxide inexpensively in a portable fashion, a technology that is in the patent process.