Scholar Profile

Danica G. Fujimori

Assistant Professor
Department of Cellular and Molecular Pharmacology/Pharmaceutical Chemistry
University of California, San Francisco
600 16th Street, Genentech Hall N572B
San Francisco, CA 94143
Voice: 415-514-0147
Personal Homepage
2011 Searle Scholar

Research Interests

Chemical Approach to Exploring Function of Histone Demethylases

Human proteome is extensively post-translationally modified by the addition of various chemical groups to side-chains of existing amino acids. The modifications (phosphorylation, acetylation, methylation, ubiquitination, SUMO-ylation, and glycosylations) control the activities, association, localization, and levels of proteins. In recent years, methylation of lysine and arginine residues has emerged as an important regulator of protein function, particularly in the context of chromatin structure and function. These methylated lysine and arginine residues are abundant in histones, which are proteins used as a scaffold for DNA packaging in the nucleus.

Histone methylation is a modification that can either activate or inhibit transcription, depending on the position and the extent of methylation of the modified residue. Like many other post-translational modifications, histone methylation is dynamic and controlled by the opposing effects of histone methyltransferases and demethylases. The largest class of demethylating enzymes in humans is the jumonji C domain-containing histone demethylases family. These enzymes are key transcriptional regulators and their misregulation by amplification, mutation, and deletion are commonly found in multiple myeloma, medulloblastoma, leukemia, and breast, prostate, renal, and esophageal cancers. Development of molecules that can modulate the function of demethylases thus represents a potential approach to targeting aberrant transcription in cancer.

By combining enzymology and chromatin biochemistry with synthetic and protein modification chemistry, we are pursuing our goal to interrogate the biological function of the jumonji family of histone demethylases. Specifically, we aim to develop specific, small molecule inhibitors of these enzymes and define parameters that control their substrate selectivity and activity. Additionally, our lab is developing histone modification techniques to allow for site-selective introduction of arginine methyl marks.