The chronic use of beta2-adrenergic agonists may be associated with deterioration of asthma control and an increase in nonspecific bronchial responsiveness. This worsening in clinical status may be related to receptor densitization after prolonged exposure to agonist. The beta2-adrenoceptor (beta2-AR) couples to its effector, adenylyl cyclase, via a signal tranducing Gs protein. With agonist binding, there is rapid uncoupling of receptor from its Gs protein due to receptor phosphorylation. Within minutes, there is loss of membrane receptors due to endocytosis into early endosomes. With prolonged exposure to agonist, there is a loss of total cellular receptor. The candidate has completed a fellowship in pediatric pulmonology and is currently on the faculty of Baylor College of Medicine with the academic rank of assistant professor. He has been involved in basic research since 1991 and has been studying the cellular regulation of beta2AR trafficking since June 1993. He has a strong desire to further develop the essential research skills necessary for a productive academic career. It is hoped that the experience and training gained during the duration of this grant will allow Dr. Moore to become an independent investigator eligible for future NIH funding. Both Drs. Dickey and Knoll hold joint appointments in the Departments of Medicine and Cell Biology, where they are actively involved in teaching programs. These departments exemplify the rich environment in cell and molecular biology at Baylor, with original research of department members regularly appearing in premiere journals, pioneering technologies under development in several laboratories, and a highly competitive graduate school program. Through bench training under the supervision of Drs. Dickey and Knoll, participation in several molecular biology courses in the Baylor Graduate School, weekly attendance of the Cell Biology Research Symposium, and Dr. Richard Clark's weekly laboratory meeting, the candidate will have the opportunity to mature as a basic science investigator in a structured environment.
