Dale F. Mierke

Academic Appointments

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. He moved to take up positions in Chemistry and Molecular Pharmacology at Brown University in 1998, then came to Dartmouth in 2007.

Contact

(603) 646-1154
202 Burke
HB 6128

Education

  • B.S. University of California at Irvine
  • Ph.D. University of California at San Diego

Selected Publications

  • Ahn KH, Bertalovitz, AC, Mierke DF, Kendall DA. (2009) Dual role of the second extracellular loop of the cannabinoid receptor 1: ligand binding and receptor localization. Mol Pharmacol. 76 833-42. PMID. 19643997

  • Thomas BE, Sharma S, Mierke DF, Rosenblatt M. (2009) Parathyroid Hormone (PTH) and PTH Antagonist Induce Different Conformational Changes in the PTHR1 Receptor. J Bone Miner Res. 24 925-34. PMID. 19063682

  • Ahn KH, Pellegrini M, Tsomaia N, Yatawara AK, Kendall DA, Mierke DF. (2009) Structural analysis of the human cannabinoid receptor one carboxyl-terminus identifies two amphipathic helices. Biopolymers 91565-73. PMID. 19274719

  • Thomas, B., Woznica, I., Mierke, DF, Wittelsberger, A., Rosenblatt, M (2008) Conformational changes in the PTH receptor associated with activation by agonist. Mol Endocrinol. 22 1154-62. PMID 18258686

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Selected Works & Activities

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.

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.