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Cedric R. Clapier, Ph.D., M.Sc., B.Sc.

Languages spoken: English, French

Academic Information

Departments: Oncological Sciences - Research Associate Professor

Academic Office Information

cedric.clapier@hci.utah.edu

Research Interests

  • Chromatin
  • Gene Expression Regulation
  • Epigenetics in Cancer
  • Biochemistry

Dr. Clapier received his B.Sc. in Biochemistry and his M.Sc. (high honors) in Cellular and Molecular Biology from the Joseph Fourier University in Grenoble, France. In 1997, he was selected by the international PhD programme of the European Molecular Biology Laboratory (EMBL) located in Heidelberg, Germany. During his graduate work conducted with Prof. Peter B. Becker on chromatin remodeling, he pioneered the production and usage of recombinant chromatin in biochemical characterization of remodelers in vitro, and discovered the first direct regulation of a chromatin remodeler (ISWI) by a nucleosome feature (the histone H4 tail basic-patch). He received his PhD (highest honors) in Molecular and Cellular Biology in 2001 as a joint degree from EMBL and the Joseph Fourier University. In 2002, Dr. Clapier investigated aspects of transcription regulation by chromatin with Dr. Jerry L. Workman at Penn State University. He then did a postdoctoral training in structural biology with Dr. Christoph W. Müller at the EMBL Grenoble outstation for which he received an EMBO long-term fellowship. During his postdoctoral work, Dr. Clapier made decisive biochemical contribution leading to the crystallization and structure of the rabies virus nucleoprotein, and solved the crystal structure of Drosophila melanogaster nucleosome. In 2007, he joined the laboratory of Prof. Bradley R. Cairns at the Huntsman Cancer Institute, University of Utah, where he made landmark discoveries in the regulatory architecture and logic of chromatin remodelers. First, Dr. Clapier demonstrated that ISWI remodeler is an intrinsically active DNA translocase held in check by two newly discovered flanking regions acting as intrinsic brakes of ATPase activity and coupling, a measurement of DNA translocation efficiency. Regulated activation of the remodeler is achieved by selective inhibitions of those intrinsic inhibitions by specific nucleosomal epitopes. These discoveries ruled out the power stroke model for the mechanism of chromatin remodeling. In a separate study, Dr. Clapier demonstrated that the capacity of the SWI/SNF-subfamily of remodelers to perform nucleosome ejection, rather than sliding, is potentiated by the regulation of a continuum of DNA translocation efficiency, with the conserved Actin-Related Proteins being required for nucleosome ejection by upregulating coupling.

Dr. Clapier is currently a Research Associate Professor at the Huntsman Cancer Institute and the Department of Oncological Sciences of the University of Utah, School of Medicine. His research continues to focus on the mechanistic characterization of the regulatory architecture and logic of chromatin remodelers, as well as on the misregulations of DNA translocation resulting from mutations observed within chromatin remodelers in cancers.

Dr. Clapier has presented his research work in many international venues as the FASEB, ASBMB, Keystone and EMBO conferences. He also authored a book chapter and reviews internationally recognized as reference publications for the field of chromatin remodeling. Dr. Clapier taught ‘Epigenetics & Chromatin Remodeling’ in the ‘Nucleic Acids’ course and was a jury member for the oral exams during five years at the Graduate School of the Joseph Fourier University. He is currently a case-based learning discussion leader for first year medical students at the University of Utah, School of Medicine.

Research Statement

While all cells in an organism harbor the same genome, different cell types and functions need to be established and maintained. In parallel, to accommodate a broad variety of DNA transactions required during their life, each cell needs a dynamic and responsive access to its genome. The packaging of genomic DNA into chromatin provides an opportunity to encompass all these requirements. Among epigenetic regulators influencing chromatin, chromatin remodelers are molecular machines that dynamically sculpture diverse chromatin landscapes and change DNA accessibility by performing highly regulated ATP-dependent DNA translocation in the context of nucleosomes.

My research focuses on understanding at the molecular level the fundamental mechanisms and regulations controlling the activities of chromatin remodelers as well as their alterations in cancers with the perspective of developing new therapeutic approaches.

Education History

Doctoral Training European Molecular Biology Laboratory - Peter B. Becker, Ph.D.
Molecular and Cellular Biology
Ph.D.
Graduate Training Joseph Fourier University
Cellular and Molecular Biology
M.Sc.
Undergraduate Joseph Fourier University
Biochemistry
B.Sc.

Global Impact