David O. Ferguson, MD, PhD
Year elected: 2012
Current membership category: Active
University of Michigan
109 ZIna Pitcher Place
BSRB, Room 2067
Ann Arbor, MI 48109
United States of America
Phone: 734-764-4591
Facsimile: 734-763-2162
Email: daviferg@umich.edu

Biographical statement

The Ferguson lab studies how mammalian cells maintain a stable genome in the face of an estimated ten DNA double strand breaks per day in every dividing cell. Syndromes resulting from defective responses to double strand breaks feature cancer predisposition, immunodeficiency, neurodegeneration and developmental defects. We focus on a multiprotein complex thought to be the "central processing unit" of double strand break responses. This complex, comprised of Mre11, Rad50, and NBS1 (MRN), is mutated in Nijmegen breakage syndrome and related disorders, and frequently harbors somatic mutations in cancers of the colon, breast and elsewhere. In the canonical DNA damage response, MRN rapidly binds to broken DNA ends and subsequently activates the ATM kinase, which signals numerous cellular responses. Through generation of engineered mouse models harboring targeted mutant alleles, we are discovering previously unknown functions of MRN and thereby providing greater understanding of disease sequelae. For example, we have demonstrated that mammalian MRN is not limited to control of the ATM kinase, but possesses DNA nuclease activities that are essential for embryonic development and function with the BRCA1 tumor suppressor in a pathway of DNA repair known as homologous recombination. Recently, we have reported that MRN has important functions that lie entirely outside of DNA damage responses. This entails direct interaction between Mre11 and Cyclin Dependent Kinase 2 (CDK2), a component of the core cell cycle machinery. We are continuing to pursue the biological functions of this interaction with aims to greater understand disease mechanisms and to uncover therapeutic opportunities.

Institutional affiliations

University of Michigan Medical School (Primary)
Elizabeth K. Speliotes, MD, PhD, MPH is the representative at this institution.