The Schwinn laboratory combines molecular pharmacology approaches with translational human functional genomics to study mechanisms underlying regulation of adrenergic receptors (ARs) in health and disease, primarily focusing on regulation of alpha1ARs. The theme unifying current projects is that reproducible perioperative stress represents a unique paradigm for understanding the effects of acute and chronic stress.
Diseases such as hypertension and myocardial hypertrophy, as well as growth responses, are our main foci. Three alpha1AR subtypes exist (alpha1a, alpha1b, alpha1d); over the years we have been involved in cloning cDNAs encoding each of these subtypes from both animal and human sources, and demonstrating that alpha1aARs are present and functional in human vasculature (particularly resistance vessels and coronary arteries) and modified by age as well as other human tissues.
In order to understand mechanisms underlying these changes, our laboratory is currently examining regulation of the human alpha1aAR at transcriptional and protein levels, in the presence and absence of hypoxia. Within this context, we are pursuing an emerging line of investigation that may play a key role in the uniqueness of the alpha1aAR in continued signaling in the presence of agonist in situations where alpha1b and alpha1dARs (and indeed many G protein-coupled receptors [GPCRs]) concurrently dampen (desensitize and/or downregulate) signaling. Our laboratory has demonstrated that the alpha1aAR, but not the alpha1bAR, undergoes constitutive internalization in the absence of agonist, suggesting internalization of alpha1aARs may use alternative trafficking pathways.