We are working to decipher the mechanism and function of integral membrane proteins involved in human disease and the means by which drug molecules and antibodies activate and inhibit function. Specifically, small molecular chaperones are known to improve the folding of the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR), to alleviate symptoms and increase the life expectancy of CF patients. Small drug molecules also show great promise in reversing multi-drug resistance and inflammation through several proteins that belong to the mega-class of ATP-Binding Cassette (ABC) transporters in humans.Most efficacious pharmaceutical agents must be identified through time-consuming and expensive high-throughput drug screens and functional assays. Approximately one-third of FDA-approved drugs target membrane proteins, yet a structure-based drug design strategy is precluded until three-dimensional crystal structures of the human membrane proteins become available. We aim to overcome this hurdle by solving high-resolution x-ray crystal structures of human membrane proteins in complexes with molecular chaperones, pharmaceutical molecules and other protein partners. The structures will enable a bona fide analysis of drug-protein interactions and provide three-dimensional scaffolds for in silico drug screening and next-generation drug design.Our laboratory is ideally located in the department of Pharmacology and Toxicology at UAB and the Center of Biophysical Sciences and Engineering (CBSE), which allows us to interact and collaborate with experts in both medicine and basic research located in the medical school clinic and surrounding biochemistry laboratories. Dr. Aller is also a member of the Comprehensive Cancer Center at UAB which allows us to work closely with experienced clinicians and scientists to take our research results to animal studies and clinical trials.