 |
Assistant Professor of Human Genetics Assistant Professor of Internal Medicine |
|
| 2063 BSRB 109 Zina Pitcher Place Ann Arbor, MI 48109 -2200 |
||
Our lab studies mechanisms of DNA repair and how aberrant repair processes affect genomic stability, predisposition to cancer and immune system development. The projects in the lab are focused on characterizing the non-homologous end-joining (NHEJ) pathway of DNA double strand break repair, one of the two major pathways of double strand break repair in mammalian cells. The NHEJ factors are not only required for general DNA repair, but also play critical roles during early B and T lymphocyte development and in maintaining genomic stability. Thus, mutations in the NHEJ genes are known to cause human immunodeficiency disorders and are also associated with predisposition to cancer in human patients. We use the mouse as a model system to study the biological consequences of specific targeted mutations in the NHEJ genes and to learn more about the in vivo functions of these DNA repair factors. Previous studies of NHEJ-deficient mice have provided significant mechanistic insights into the functions of the NHEJ factors in immune system development as well as in suppressing oncogenic chromosomal events that predispose the mutant mice to lymphoid neoplasias. Currently, we are using a combination of biochemical, cellular and genetic approaches to gain additional insights into the specific functions and activities of the NHEJ factors during DNA repair and lymphocyte development. We are particularly interested further characterizing the NHEJ gene, Artemis, as recent evidence suggests that different mutations cause distinct disease outcomes in human patients. Specifically, inactivating mutations in Artemis cause a human severe combined immunodeficiency associated with extreme cellular radiosensitivity and hypomorphic mutations are associated with predisposition to lymphoid neoplasia.
Mar., 2004 Pew Scholar in Biomedical Sciences, Pew Charitable Trust Foundation
Sept., 2003 Biomedical Sciences Scholar Award, University of Michigan
Dec., 2002 Ranadive Endowment Award, Leukemia and Lymphoma Society
June, 1999 Richard D. Frisbee III Foundation Fellow, Leukemia and Lymphoma Society
June, 1998 Young Investigator Award; FASEB Summer Conference-Nucleic Acid Enzymes
May, 1995 Frank Lappin Horsfall, Jr. Fellowship; Sloan-Kettering Institute
1996 Cornell University Graduate School of Medical Sciences, Ph.D. Molecular Biology
1987 University of California, Davis, B.S. Biochemistry
1987 University of California, Davis, B.A., Psychology
Sekiguchi, J. M. and D. O. Ferguson (2006) DNA double-strand break repair: A relentless hunt uncovers new prey. Cell, 124:11-12.
Rooney, S., Alt, F. W., Sekiguchi, J. and J. P. Manis (2005) Artemis-independent functions of DNA-dependent protein kinase in IgH class switch recombination and development. Proc Natl Acad Sci, USA. 102:2471-2475.
Rooney, S., Sekiguchi, J., Whitlow, S., Eckersdorff, M., Manis, J. P., Lee, C., Ferguson, D. O., and F. W. Alt (2004) Artemis and p53 cooperate to suppress oncogenic N-myc amplification in progenitor B cells. Proc. Natl. Acad. Sci., USA. 101:2410-2415.
Sekiguchi, J., Alt, F. W., and M. A. Oettinger (2003) The mechanism of V(D)J recombination. pp. 57-78. In Molecular Biology of B cells, ed. Alt F. W. and T. Honjo, Elsevier Science, USA.
Dudley, D. D., Sekiguchi, J., Zhu, C., Sadofsky, M. J., Whitlow, S., DeVido, J., Monroe, R. J., Bassing, C. H. and F. W. Alt (2003) Impaired V(D)J recombination and lymphocyte development in core RAG1-expressing mice. J. Exp. Med., 198:1439-1450.
Rooney, S., Alt, F. W., Lombard, D., Whitlow, S., Eckersdorff, M., Fleming, J., Fugmann, S., Ferguson, D. O., Schatz, D. and J. Sekiguchi (2003) Defective DNA repair and increased genomic instability in Artemis-deficient murine cells. J. Exp. Med, 197:553-565.
Rooney, S., Sekiguchi, J., Zhu, C., Cheng, H.-L., Manis, J., Whitlow, S., DeVido, J., Foy, D., Lombard, D., and F. W. Alt (2002) Leaky scid phenotype associated with defective V(D)J coding end processing in Artemis-deficient mice. Mol. Cell, 10:1379-1390.
Sekiguchi, J., Whitlow, S. and F. W. Alt (2001) Increased accumulation of hybrid V(D)J joins in cells expressing truncated versus full-length RAGs. Mol. Cell, 8:1383-90.
Home