Raymond J. Monnat Jr., MD

NGEC Principal Investigator

Professor of Genome Sciences and Pathology
University of Washington

Department of Biochemistry
University of Washington School of Medicine
Health Sciences K-072C, Box 357705
1959 NE Pacific St.
Seattle, WA 98195
Tel: 206-616-7392; Fax: 206-543-3967

E-mail Dr. Monnat

Dr. Monnat is a professor in the Departments of Pathology and Genome Sciences at the University of Washington. His laboratory studies the role of genetic insability in cancer risk and pathogenesis, and he has had a longstanding interest in the use of homing endonucleases as tools for targeted induction of double strand breaks. Specific ongoing projects in his lab address instability mechanisms in the human RecQ helicase deficiency syndromes, control of large scale gene rearrangements, double strand break DNA repair, and the spectrum and frequency of somatic mutations in vivo.

Dr. Monnat is the principal investigator for the NGEC in the area of novel homing endonucleases for genome engineering.
 

Awards and Honors

• Experimental Pathologist-in-Training Award, American Association of Pathologists: 1984
• Outstanding Teaching Award (from 1990 Entering Class of the University of Washington School of Medicine): 1991
• Exemplary Leadership in Teaching Award, University of Washington School of Medicine (University of Washington Chair and plaque awarded): 1997
• Distinguished Service Award, Fanconi Anemia Research Fund: 2004

Areas of Expertise

• Human RecQ helicase deficiency syndromes, such as Werner syndrome
• Homing endonucleases and their use as genome engineering reagents
• Human somatic mutation

Research Interests

• Werner Syndrome
• DNA Replication Dynamics
• Homing Endonucleases

Overview of the Monnat Lab

The Monnat Laboratory research focuses on molecular mechanisms that insure the faithful transmission of genetic information in human somatic cells, and on the generation of novel genome engineering reagents for biology and medicine. The lab conducts research in two key areas:

Genetic stability mechanisms
The Monnat Lab works on a small gene family, the human RecQ helicases, which play key roles in nucleic acid metabolism and genetic stability assurance. Loss of function of three of these proteins, WRN, BLM and RECQ4, are associated with the heritable genetic instability/cancer predisposition diseases Werner, Bloom and Rothmund-Thomson syndromes. Research at the lab is focused on in vivo functions of these proteins, on regulation and on functional redundancy between different members of the human RecQ helicase family.

Genome engineering
Homing endonucleases are highly site-specific endonucleases that catalyze the lateral transfer of parasitic DNA elements in all Kingdoms of life. Dr. Monnat and his team have characterized structures and target site specificities of members of two families of these proteins, and have used results to engineer novel chimeric homing endonucleases with altered target site specificities. These new gene-specific reagents are being used for genome engineering, and have potential for disease therapy and prevention.
 

NGEC Research

Homing As part of its role in the NGEC, the Monnat Laboratory is working to:

1. Develop and optimize new LAGLIDADG homing endonucleases (LHEs) for human genome engineering applications.
2. Develop and validate target gene-specific LHEs that cleave human/mammalian disease gene targets in living cells.
3. Demonstrate LHE cleavage-induced recombination to repair of disease gene mutations in human, mouse and canine target cells.

The Monnat Lab has had a very longstanding interest in using homing endonucleases for both fundamental biology and for disease research and therapy. The NGEC is a realization of Dr. Monnat and his team’s original work over the past 15 years to identify and develop homing endonucleases as genomics reagents. The lab seeks to answer questions such as: What new proteins can be found in nature? What new proteins can be engineered from nature’s “starter set”? What are the functional properties of HEGs as genome engineering reagents in mammalian cell?

Key personnel carrying out this research include Hui Li (postdoctoral fellow), Stefan Pellenz (postdoctoral fellow) and Blake Hovde (graduate student).

Publications