Van der Vliet Bio

My research interests are centered around the involvement of oxidants in the etiology of chronic airway diseases such as asthma, cystic fibrosis, and emphysema. The activation of inflammatory-immune processes is common to all these diseases, and cells of the inflammatory-immune system are equipped with mechanisms to produce a range of reactive oxygen metabolites, as part of the host defense system. However, abnormal regulation of such inflammatory-immune processes (by environmental or genetic factors) can result in inappropriate production of these reactive oxygen metabolites, which can also affect host cell biology in many ways. Central to my research is the identification and analysis of biological markers that are characteristic of the generation of specific inflammatory oxidants, and the identification of cellular and extracellular targets of these oxidants, which can provide mechanistic links between the generation of inflammatory oxidants and its biological consequences. Furthermore, identification of the specific nature of the involved oxidants and of their cellular and enzymatic sources may also contribute to development of additional or alternative approaches to manage such airway diseases.

My research currently focuses on the following two general areas:

1. The role(s) of nitric oxide in the regulation of airway inflammation. This inflammatory mediator interacts in many ways with the activation of inflammatory processes and with the formation of reactive oxygen metabolites. Such interactions impact on the biological activity of nitric oxide, and affect typical post-translational modifications such as S-nitrosation and tyrosine nitration. Proteomics approaches are used to identify cellular targets for such modifications. We are especially interested in the involvement of nitric oxide in the regulation of cell surface receptors in the lung, such as epidermal growth factor receptor, and of proteolytic enzymes such as matrix metalloproteinases. These systems are of critical importance in repair processes following airway injury, and are known to be susceptible to oxidant regulation with potential implications for chronic structural changes in the lung (airway remodeling) seen in relation to chronic airway inflammation.
   
   
2. Environmental factors (allergens, pollutants, tobacco smoke) are known to contribute to chronic airway diseases such as asthma or emphysema, and we are studying effects of environmental pollutants (such as reactive aldehydes) on the regulation of inflammatory cell activation and apoptotic cell death. Dysregulation of these events, that are crucial in the control of the inflammatory process and its resolution, can be expected to contribute to a persistent inflammatory response.