Steve Jacobsen, Ph.D.

Steve Jacobsen, Ph.D., studies DNA methylation and epigenetic gene regulation, processes that play important roles in development and genome integrity. He seeks to apply his findings to develop more effective cancer therapies and improved CRISPR-based tools for gene editing.

The most common form of epigenetic gene regulation, and a focus of Jacobsen’s research, is DNA methylation — a naturally occurring process by which cells silence specific genes by chemically attaching methyl groups to their surface. DNA methylation is fundamental to controlling cell growth and development, and is important in some cancers. 

A trained plant biologist, Jacobsen uses plants such as Arabidopsis thaliana, as well as mammalian stem cells, to study these gene regulatory processes. His research focuses on the mechanisms by which DNA methylation, histone methylation and non-coding RNAs converge in overlapping pathways to promote stable and heritable repression of gene transcription.

Understanding the mechanisms used to turn genes on and off could advance our understanding of developmental transitions and assist in the development of improved cancer therapies, among other advances. Insights gained from this research could also inform the development of improved CRISPR-based tools for gene editing and for the targeting of epigenetic marks to specific loci.

He has made several key findings about DNA methylation in stem cells. Alongside center members Amander Clark, Ph.D., and Matteo Pellegrini, Ph.D., Jacobsen demonstrated that a protein called UHRF1 plays a critical role in DNA methylation control in mammals. He was also among the first researchers to illuminate the role of histone methylation in directing DNA methylation, detailing a positive feedback loop that shows how DNA methylation, once established, can be faithfully maintained. 

Jacobsen is a Howard Hughes Medical Institute Investigator and an elected member of the National Academy of Sciences.