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, as well as molecular modeling of these complexes
• Use of fluorescence to probe microdomains involved in CCK ligand binding, as well as 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 for the control of 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, as well as molecular modeling of these complexes
• Use of fluorescence to probe microenvironments involved in secretin ligand binding, as well as 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, as well as 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 for the management of diabetes and obesity