University of Washington     Department of Pharmacology



Regulation of Gene Expression in Cell Proliferation, Muscle Differentiation and Human Disease

The expression of protein encoding genes is essential for the proper execution of all cellular processes.  My lab focuses on understanding the role of gene transcription in cell cycle progression, muscle formation and human disease.  We are particularly interested in the molecular mechanisms and signaling pathways governing the transcription of the cell cycle control gene cyclin D1.  The overexpression of cyclin D1 is found in many human tumors, including breast cancer, and is often associated with a poor prognosis.  The major objective of our work is to gain a better understanding of the pathways controlling cyclin D1 promoter activity and to use this information to uncover new therapeutic targets for anti-cancer drugs.

Disruption of gene transcription can lead to the development of human disease.  We have focused on myotonic dystrophy, the most common form of adult onset muscular dystrophy.  Myotonic dystrophy is genetically linked to nucleotide repeat expansions in the noncoding region of two unrelated genes.  The expanded mutant RNA transcripts accumulate in the nuclei of diseased cells and alter the expression of genes essential for muscle formation, maintenance and function.  We use a variety of molecular, biochemical, and cellular techniques to investigate the protein components regulating muscle gene expression under normal and pathologic conditions.  Our long-term goal is to gain a better understanding of the molecular mechanisms that contribute to disease onset and to evaluate potential therapeutic approaches for combating muscle weakening and wasting experienced by myotonic dystrophy patients.