Projects

Dr. Miller's lab studies the class A cholecystokinin receptor and the class B secretin receptor, with a goal of advancing the development of receptor-active drugs.

Class A G protein-coupled receptor (GPCR) projects

• Use of photoaffinity labeling and mutagenesis to explore the molecular basis of natural cholecystokinin (CCK) ligand binding to its receptor.
• Refine the understanding of the structure of ligand-receptor complexes in active and inactive states and molecular modeling of these complexes.
• Use of fluorescence to probe microdomains involved in CCK ligand binding and conformational changes associated with receptor activation.
• Use of cryogenic electron microscopy (cryo-EM) for the structural characterization of states of the CCK receptors.
• Structure-based rational design and optimization of CCK receptor-active drugs, including both orthosteric and allosteric ligands.
• Analysis of the impact of the lipid microenvironment on CCK receptor structure and function.
• Applications of CCK receptor-active drugs to control appetite and obesity.

Class B GPCR projects

• Use of photoaffinity labeling and mutagenesis to explore the molecular basis of natural secretin ligand binding and activation of its receptor and molecular modeling of these complexes.
• Use of fluorescence to probe microenvironments involved in secretin ligand binding and conformational changes associated with receptor activation.
• Use of cryo-EM for the structural characterization of states of the secretin receptor.
• Analysis of the quaternary structure of receptor complexes, including dimerization and oligomerization and association with other regulatory proteins.
• Evaluation of the molecular basis of drug action and definition of "druggable" pockets within class B GPCRs.
• Application of class B GPCRs and receptor-active drugs to manage diabetes and obesity.