Steven Jacobsen, PhD

Steven Jacobsen, Ph.D. 

Distinguished Professor, Molecular, Cell and Developmental Biology; Professor, Biological Chemistry

Bio

Steve Jacobsen, Ph.D., focuses on epigenetics – the study of biological mechanisms that regulate gene expression (switching genes on) and silencing (switching genes off) without changing the fundamental DNA sequence. The most common form of epigenetic gene regulation 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. DNA methylation also helps maintain a stem cell’s pluripotency, or ability to develop into any cell in the body, and guides stem cells as they differentiate, or transform into specialized cells. Jacobsen hopes his research on epigenetic gene regulation will lead to new and improved methods for the development of stem cell therapies and a better understanding of how epigenetic defects contribute to cancer and other diseases.

Beginning his career as a plant biologist, Jacobsen expanded into human stem cell research because stem cells are tolerant to dramatic losses of DNA methylation and gene silencing processes, which makes them an ideal model for studying these mechanisms. He has made several key findings about DNA methylation in stem cells. Along with stem cell center collaborators including Amander Clark and Matteo Pellegrini, Jacobsen discovered a relationship between methylation and the positioning of nucleosomes, which compact and regulate access to DNA in the nucleus of a cell. He also identified a protein called UHRF1 that plays a critical role in maintaining DNA methylation. Finally, he generated one of the first genome-wide mapping datasets for 5-hydroxymethylcytosine (5hmC) — a DNA modification in human embryonic stem cells – and discovered that it is found primarily in genes that are active. These findings could have implications in fighting cancer, which is generally a problem of genes being inappropriately silenced, activated or mutated.

Jacobsen continues to use plants such as Arabidopsis thaliana, a small flowering plant from the mustard family, to study methylation and other forms of epigenetic gene regulation. Studying Arabidopsis, his lab discovered a new family of proteins called MORCs that bind to DNA and provide instructions to keep DNA silent. Jacobsen then turned his attention to studying the role of MORCs in animal stem cells, discovering that these proteins are critical for keeping repetitive regions of DNA silent, and that disrupting these proteins caused failed stem differentiation. He and his collaborators are now focused on studying one of these proteins in particular, MORC-1, to better understand the role it plays in the development of male germline cells, which create sperm cells. They have found that mutations to this protein cause problems in male germline cell differentiation, which can lead to infertility. The group is continuing to study MORCs with the ultimate goal of discovering new treatments for conditions associated with their mutation. Much of the research described above was accomplished using a technique Jacobsen developed– called whole genome bisulfite sequencing – that enables profiling of DNA methylation at single nucleotide resolution. 

Jacobsen earned a doctorate in plant biology from University of Minnesota and completed a post-doctoral fellowship in plant developmental genetics at the California Institute of Technology. He was named a Howard Hughes Medical Institute Investigator in 2005 and was elected to National Academy of Sciences and American Academy of Arts and Sciences in 2011 and 2016, respectively.

Publications

Honors & Affiliations

Honors

  • Elected Member, American Academy of Arts & Sciences, 2016
  • Elected Member, National Academy of Sciences, 2011
  • Charles Albert Shull Award, American Society of Plant Biologists, 2009
  • Phillip C. Hamm Memorial Lecture Award, University of Minnesota, 2008                         
  • Elected Fellow, the American Association for the Advancement of Science, 2004

Affiliations

  • Investigator, Howard Hughes Medical Institute
  • Genetics Society of America
  • Plant biology investigator selection committee,  Howard Hughes Medical Institute
  • Editorial board, Epigenetics and Chromatin, Silence, Genetics and Epigenetics, Epigenomics, and Current Biology

Funding

Jacobsen's work is funded by the National Institutes of Health, the Bill and Melinda Gates Foundation and the Howard Hughes Medical Institute.