MERIT Award Recipient: Peter A. Jones, Ph.D., D.Sc.

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Sponsoring NCI Division: Division of Cancer Biology (DCB)
Grant Number: R37 CA082422-12
Award Approved: June 2009
Institution: University of Southern California
Department: Director of the University of Southern California/Norris Comprehensive Cancer Center
Peter A. Jones, Ph.D., D.Sc.
Literature Search in PubMed

Mechanisms of De Novo Methylation in Cancer

It has become clear over the last several years that the abnormal silencing of genes, via chemical modifications of cells' chromosomal DNA molecules, can contribute directly to the formation of human cancer. We know that altered patterns of DNA methylation (one type of chemical DNA modification) play a fundamental role in the silencing of tumor suppressor genes, but we do not yet know how these altered patterns are set up, or how normal patterns are established and inherited during human development. Our research is focused on understanding how DNA methylation patterns interact with other components of the chromosomes (including proteins and small RNA molecules) to regulate gene expression in normal cells and in cancer. We are conducting a holistic approach in which we are more interested in the regulation of the interactions among chromosomal components than in the individual components and DNA modification processes themselves. We rely heavily on the use of drugs that we originally defined as being inhibitors of DNA methylation and therefore inducers of gene expression. Importantly, these drugs have now been approved by the FDA for the treatment of human cancer; understanding exactly how they work should lead to the development of better therapies for cancer.