Dale F. Mierke
Professor of Chemistry
Frank R. Mori Professor
The major thrust of the Mierke research group is the identification and development of molecules to inhibit protein/protein interaction towards therapeutic intervention in several different diseases. We employ an array of biophysical techniques for the structural characterization of the targets (namely nuclear magnetic resonance) followed by in vitro screening of compounds for inhibitory biological function, using NMR and fluorescence anisotropy.
We are currently designing molecules that inhibit formation of the DISC (death Inducing signaling complex) important in the regulation of apoptosis, with particular efforts placed on blocking the recruitment of cFLIP to the DISC, and thereby restating the extrinsic apoptosis signaling. Another project entails screening for direct inhibitors of the GTPase Rac1 oncogenic protein, employing a novel NMR-based GTP turnover assay. A final project aims at the identification of molecules to inhibit the NEMO/IKK association and thereby a novel method for therapeutic intervention.
- B.S. University of California at Irvine
- Ph.D. University of California at San Diego
- Post-Doc/Fulbright Fellow, Technical University of Munich
Panaitiu, A., Basiashvili, T., Mierke, D.F. Pellegrini, M. (2022) An engineered construct of cFLIP provides insight into DED1 structure and interactions. Structure, 30, 2, 229-239. PMID: 31929506.
Yang, S. Larsen, D. Pellegrini, M. Meier, S. Mierke, DF, Beeren, S. Aprahamian, I. (2021) Dynamic enzymatic synthesis of γ-cyclodextrin using a photoremovable hydrazone template. Chem. 7, 2190-2200.
Barczewski, A., Regusa, M., Mierke, D.F. Pellegrini, M. (2019) The IKK-binding domain of NEMO is an irregular coiled coil with a dynamic binding interface. Sci Rep. 9 2950. PMID: 30814588.
Selected Works & Activities