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 projects

  • Development of drugs targeting the cholecystokinin (CCK) receptor.
  • Use of photoaffinity labeling and mutagenesis to explore the molecular basis of ligand binding to the CCK 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 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 G protein-coupled receptor projects

  • Development of drugs targeting class B G protein-coupled receptor 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 cryogenic electron microscopy 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 G protein-coupled receptors.
  • Application of class B G protein-coupled receptors and receptor-active drugs to manage diabetes, obesity, and heart failure.