Research Interests

As a geneticist, I have been attracted to issues of gene regulation, cell biology and genomics in organisms ranging from yeast to human. I discovered the four Sir genes of yeast which are responsible for forming heterochromatin at specific positions in the genome. With members of my lab, we discovered the epigenetic inheritance of silenced chromatin. We discovered the first mutations in the Origin Recognition Complex and established their link to DNA replication and to silencing. We discovered the spreading of heterochromatin from silencers, and established the mechanism of spreading through biochemical studies as well as genetic studies at the single-cell level. We also discovered the enzymes responsible for the prenylation of Ras and other G proteins, and a pair of proteases that trim the ends of prenylated proteins. These activities proved to be essential for the activated phenotypes of oncogenic mutations in Ras. I was also the founder of Dog Genome Project, and led the team that developed the first complete genetic map of the Dog. More recently, I have turned my attention to the interpretation human genetic variation, to the discovery of cofactor remedial mutations, and to nutritional links to human epigenetic events.

Membership Type


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Primary Section

Section 26: Genetics

Secondary Section

Section 41: Medical Genetics, Hematology, and Oncology