Laurence J. Miller, M.D., is director of the HEALTH Program and a member of the Division of Gastroenterology and Hepatology at Mayo Clinic in Arizona. He is also a professor of biochemistry and molecular biology and a professor of medicine in the College of Medicine, Mayo Clinic.
G protein-coupled receptors and drug development
Dr. Miller's longstanding research focus has been in the area of G protein-coupled gastrointestinal hormone receptor structure, function and regulation. This has focused on cholecystokinin (CCK)-gastrin and secretin-vasoactive intestinal polypeptide (VIP)-glucagon-like peptide families of peptides and receptors. These receptors are important for nutritional homeostasis, digestion, metabolism and cell growth.
Dr. Miller's most unique contributions to this area have been in applying photochemistry and molecular pharmacological techniques to probe the molecular basis of drug action and the three-dimensional structure of ligand-receptor complexes. This has substantial implications for the development of receptor-active drugs that possess unique selectivities and spectra of biological activities. This has provided unique opportunities to impact obesity, diabetes, and various malignant tumors of the pancreas and colon.
Dr. Miller is also an expert in areas of receptor signaling and receptor regulation by biochemical and cellular mechanisms. These often differ in distinct types of cells, as well as in pathological states versus healthy cells. Characterization of these processes has provided still other potential opportunities for therapeutic interventions in these diseases.
This work also has major implications for the development of diagnostic and prognostic biomarkers, selective imaging agents and therapeutic targeting.
Significance to patient care
G protein-coupled receptors are the largest group of cell surface receptors, as they are present on virtually every excitable cell in the body. As such, they also represent the predominant target for existing approved drugs.
Dr. Miller's work is key for understanding how drugs work, as it provides molecular insights that are useful for the development of new drugs that are better, safer and more effective. These are relevant to a broad variety of diseases, many of which are quite common and have major impacts.
- Editorial Board, Journal of Biological Chemistry, 2010-present
- Editorial Board, Molecular Pharmacology, 2002-present
- Member, NIH Study Sections — Gastrointestinal Cell and Molecular Biology, 2007-2009; Clinical Integrative and Molecular Gastroenterology, 2009-2011