- Staff Scientist/Post-Doctoral Fellow, 1998-2003, ETH-Zürich, Institute of Molecular Biology & Biophysics
- Post-Doctoral Fellow, 1996-1997, University of Miami, Dept. of Chemistry
- Ph.D. in Biochemistry & Molecular Biology, 1991-1996, University of Miami School of Medicine, Dept. of Biochemistry & Molecular Biology
- B.A. in Biochemistry, 1987-1991, University of Colorado
- B.A. in Psychology, 1987-1991, University of Colorado
- Chromatin-targeting drug development
- Structure/activity of nucleosomes and other chromatin factors
The overall focus of my laboratory is the role of chromatin structure, composition and dynamics in genomic regulation, with a research strategy of pushing both basic and pharmaceutical fronts. My main initiative has been building up a comprehensive chromatin-targeting anticancer drug development platform, which now involves many investigators worldwide. The approach encompasses structural, computational, analytical chemistry, biochemical and biophysical studies on nucleosomes and chromatin fiber, as well as cell function and cell imaging experiments, to assess the influence of drug binding on the structure and regulation of chromatin and to elucidate the site selectivity and localization of drugs at the cellular level.
The details of the involvement of nucleosome structure and dynamics in genomic regulation are becoming increasingly clear, but we still lack an understanding of how DNA-binding proteins recognize their target sites within a chromatin context. In conjunction with the chromatin drug studies, we are investigating influence on chromatin structure/activity and nucleosome recognition by architectural nuclear proteins and different DNA repair, apoptotic and developmental DNA sequence-specific transcription factors. These projects are aimed at structure and dynamics characterization of chromatin fiber– and nucleosome–protein factor interactions, which may reveal fundamental mechanistic principles as well as new therapeutic targets.
- DNA sequence-dependence of nucleosome positioning, structure & stability
- Small molecule targeting of chromatin
- Development of metal-based anticancer drugs
- Modulation of chromatin structure & dynamics by drugs and nuclear factors
- Site-specific recognition of nucleosomes by transcription/repair/architectural factors