Dale F. Mierke
Professor of Chemistry
Professor Mierke received his B.S. degrees in Chemistry and in Biological Sciences from the University of California, Irvine in 1984. He received his Ph.D. in 1988 working with Professor Murray Goodman at the University of California, San Diego. Postdoctoral studies took him to the Biopolymer Research Institute in Padova and as a Fulbright Scholar from 1990 - 1993 to work with Horst Kessler at the Technical University of Munich. Professor Mierke joined the faculty at University of Massachusetts, Medical School (Dept Pharmacology) and Clark University (Dept. Chemistry) in 1993, moving to take up positions in Chemistry and Molecular Pharmacology at Brown University in 1998. Prof. Mierke will join the faculty of Dartmouth College in the summer of 2007.
Research Interests
Research in our laboratory aims to establish the structural basis of the mechanism of action of different peptide hormones. Particular emphasis has been placed on delineation of the interaction of the hormones with their G-protein coupled receptors employing a combination of spectroscopic techniques (NMR, EPR, fluorescence, CD), photoaffinity labeling, and extensive computer simulations. The structures provided from these efforts have facilitated the rational design of molecules with enhanced potency, receptor specificity, and duration of action.
Parathyroid hormone, a major regulator of calcium levels in blood and important target for the treatment of osteoporosis, interacting with the PTH G protein coupled receptor.
Our laboratory is also targeting molecular scaffolds, multidomain proteins that regulate transmembrane receptor trafficking and lifetime as possible targets for cystic fibrosis, osteoporosis, and drug addiction. High-resolution NMR methods provide structural features of the protein domains, both while free and bound to the target receptor. Using novel computational approaches, this information is used to design and optimize small molecule inhibitors of the protein/receptor association.
NMR-derived structure of the PDZ1 domain of synaptic associated protein-97 bound to the C-terminus of the NR2B subunit of the NMDA glutamate receptor.