Inflammation is a common mediator of many chronic human diseases, including asthma, heart disease, aging, and cancer. I am interested on how cellular signaling pathways induce inflammation with the goal of being able to monitor and modulate these pathways to treat these conditions.
One of our major areas of concentration is to understand intracellular signaling pathways control a "master" regulator of inflammation known as nuclear factor-kB (NF-kB). We have shown that NF-kB is a mediator for respiratory virus- induced pulmonary inflammation, one of the important links between acute respiratory infections and asthma exacerbations. In recent work we have found that cyclin dependent kinases are critical for some of the inflammatory activities of NF-kB. We are currently investigating whether inhibition of cyclin dependent kinases can be used as anti-inflammatory agents in models of airway inflammation.
In addition, were the first group to show that a blood pressure regulating hormone, angiotensin II, produces chronic vascular inflammation via NF-kB in smooth muscle cells. In fact, vascular inflammation is now known to be a major, independent risk factor for the development of atherosclerosis. In recent work, we have further extended our findings to implicate the GTPase Rho A as a controller of angiotensin II-induced NF-kB signaling. We are currently pursuing animal studies to determine whether agents that affect the RhoA-NF-kB pathway can be used to treat vascular diseases.
Currently, we are developing exciting new proteomics technologies to identify predictive biomarkers in patients with airway disease. To this end, we recently have discovered a panel of cytokines that separate various groups of asthmatics and are seeking to validate these in independent studies. Our ultimate goal is to be able to predict treatment outcome in patients inflammatory disease as a first step towards personalized medicine.