Erik J. Sontheimer is an American molecular biologist and professor at the University of Massachusetts Chan Medical School, where he holds the Pillar Chair in Biomedical Research.[1] and is vice chair of the RNA Therapeutics Institute. His research focuses on RNA-mediated mechanisms of gene regulation, including pre-mRNA splicing, RNA interference (RNAi), and CRISPR–Cas adaptive immune systems, with implications for genome engineering and therapeutic development.
Sontheimer earned his Ph.D. in 1992 from Yale University[1], where he conducted doctoral research on pre-mRNA splicing mechanisms in the laboratory of Joan A. Steitz. His graduate work contributed to the understanding of spliceosomal structure and function, including the roles of small nuclear RNAs in catalysis. He subsequently completed postdoctoral training in biochemistry and molecular biology at the University of Chicago, working with Edwin Ferguson and later with Joseph Piccirilli[2]. Sontheimer joined the faculty of Northwestern University in 1999 as an assistant professor in the Department of Molecular Biosciences. He was promoted to associate professor in 2006 and to professor in 2012. In 2014, Sontheimer moved to the University of Massachusetts Chan Medical School, where he became a professor in the RNA Therapeutics Institute. In 2020, he was named Pillar Chair in Biomedical Research[3]. Dr. Sontheimer has more than 27,000 citations on Google Scholar[4].
Research contributions
RNA splicing and catalysis
Early in his career, Sontheimer developed and applied site-specific RNA crosslinking and “atomic mutagenesis” approaches to study spliceosome structure and function. This work provided evidence that small nuclear RNAs participate directly in the spliceosomal active site and helped establish the role of metal ions in pre-mRNA splicing catalysis[5][6]. His later research as a principal investigator examined regulatory mechanisms governing spliceosome assembly and dynamics, including the involvement of ubiquitin-mediated processes.
RNA interference and small RNA pathways
Beginning in the early 2000s, Sontheimer contributed to the mechanistic understanding of RNA interference (RNAi) with student, John Pham, in collaboration with Richard Carthew. His research helped distinguish the roles of distinct Dicer enzymes in microRNA and small interfering RNA pathways and characterized key steps in the assembly and function of RNA-induced silencing complexes[7].
CRISPR–Cas systems and genome engineering
Sontheimer’s laboratory made foundational contributions to the study of CRISPR–Cas adaptive immune systems in bacteria. In 2008, he and postdoc Luciano Marrafini reported that CRISPR–Cas pathways can destroy DNA[8][9][10][11], advancing understanding of CRISPR interference and its role in limiting horizontal gene transfer. Subsequent work addressed mechanisms of self–non-self discrimination in CRISPR immunity and the diversity of guide RNA biogenesis strategies[12]
Sontheimer's subsequent research focused on Type II CRISPR–Cas9 systems, including compact Cas9 orthologs with properties favorable for genome engineering. His laboratory also co-discovered naturally occurring anti-CRISPR proteins and demonstrated their utility as molecular regulators of CRISPR activity[13][14][15]. Additional work expanded genome-editing and genome-analysis tools, including approaches for improving delivery, specificity, and control of CRISPR-based systems.
Elected to the American Academy of Microbiology, 2016[18]
Nestlé Award, American Society for Microbiology, 2008
Weinberg College of Arts and Sciences Distinguished Teaching Award, 2005
American Cancer Society Scholar Award, 2004
Basil O’Connor Starter Scholar Research Award, March of Dimes Foundation, 2001
National Science Foundation CAREER Award, 2001[19]
Burroughs Welcome Fund New Investigator Award in the Pharmacological Sciences, 2000
Fellow, The Jane Coffin Childs Memorial Fund for Medical Research, 1993-1996[20]
Service and editorial roles
Sontheimer has served in national scientific leadership and advisory roles, including membership on the National Cancer Institute Board of Scientific Counselors, where he served as co-chair from 2021 to 2023. He also served as co-chair of the Steering Committee for the National Institutes of Health Somatic Cell Genome Editing Program[21][22]. He has held editorial positions with several scientific journals, including RNA, Human Gene Therapy, EMBO Reports, and The CRISPR Journal, and has served on governance and review panels for the RNA Society and the National Institutes of Health.
Involvement with biotechnology
In 2014, Sontheimer co-founded Intellia Therapeutics[23], a biotechnology company focused on the clinical development of CRISPR-based gene-editing technologies. He serves as a scientific advisor for Tessera Therapeutics[24] and has also participated in advisory roles for other biotechnology organizations.
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