Nathan Ames Ellis
Research Summary / Selected Publications
We study the mechanisms that maintain genomic integrity and the relationship between genomic instability and cancer susceptibility. Our interests span high-penetrance and low-penetrance cancer-causing genes, population genetics of human cancer susceptibility alleles, and the molecular and cellular biology of the cancer susceptibility genes themselves.
BLM meets SUMO: wrestling with genomic instability and nuclear trafficking
A major focus is the investigation of the Bloom's syndrome (BS) protein BLM and of the mechanisms of maintenance of genomic integrity in which BLM operates. BLM is modified by the protein SUMO, which stands for small ubiquitin-like modifier. Normally BLM is localized to PML nuclear bodies (PML-NBs) and, in response to DNA damage, particularly during S phase, BLM will migrate from the PML-NBs and concentrate focally in DNA damage induced foci (DDI foci). Sumoylation-deficient BLM concentrates constitutively in DDI foci in the absence of DNA damage, indicating that negatively regulates BLM s trafficking to DDI foci. Our data show that BLM can function as a sensor of DNA damage, and we are interested in identification of factors that bind to BLM and regulate DDI focus formation.
Low-penetrance colon cancer genes
A second major focus is directed towards identification of novel colorectal cancer (CRC)-causing genes by association studies of biologically relevant candidate genes and by analysis of candidate genes identified in genome-wide single-nucleotide polymorphism (SNP) screens. The genetic model that best describes the genetic variance that remains after the known high-penetrance CRC susceptibility genes are eliminated is multi-factorial low-penetrance alleles that interact. We have found that high-risk families are enriched for low-penetrance factors, and we are using such families to identify new CRC-susceptibility alleles, the effects of which can be better quantified in large case-control studies.
We study the mechanisms that maintain genomic integrity and the relationship between genomic instability and cancer susceptibility. Our interests span high-penetrance and low-penetrance cancer-causing genes, population genetics of human cancer susceptibility alleles, and the molecular and cellular biology of the cancer susceptibility genes themselves.
BLM meets SUMO: wrestling with genomic instability and nuclear trafficking
A major focus is the investigation of the Bloom's syndrome (BS) protein BLM and of the mechanisms of maintenance of genomic integrity in which BLM operates. BLM is modified by the protein SUMO, which stands for small ubiquitin-like modifier. Normally BLM is localized to PML nuclear bodies (PML-NBs) and, in response to DNA damage, particularly during S phase, BLM will migrate from the PML-NBs and concentrate focally in DNA damage induced foci (DDI foci). Sumoylation-deficient BLM concentrates constitutively in DDI foci in the absence of DNA damage, indicating that negatively regulates BLM s trafficking to DDI foci. Our data show that BLM can function as a sensor of DNA damage, and we are interested in identification of factors that bind to BLM and regulate DDI focus formation.
Low-penetrance colon cancer genes
A second major focus is directed towards identification...
Eladad, S., Ye T.-Z., Hu P., Leversha M., Beresten S. F., Matunis M., Ellis N. A. (2005). Intra-nuclear trafficking of the BLM helicase to DNA damage induced foci is regulated by SUMO-1. Hum Mol Genet 14:1351-65.
Mitra N., Ye T.-Z., Smith A., Chuai S., Kirchhoff T., Peterlongo P., Nafa K., Phillips M. S., Offit K., Ellis N. A. (2004). Localization of cancer susceptibility genes by genome-wide SNP linkage disequilibrium mapping. Can Res 64:8116-25.
German J., Ellis N.A. (2002). Bloom syndrome. In: The Genetic Basis of Human Cancer Vogelstein B., Kinzler K., eds. New York: McGraw-Hill, Inc., pp. 267-88.
Gruber* S. B., Ellis* N. A., Scott K. K., Almog R., Kolachana P., Bonner J. D., Kirchhoff T., Tomsho L. P., Nafa K., Pierce H., Low M., Satagopan J., Rennert H., Huang H., Greenson J. K., Groden J., Rapaport B., Shia J., Johnson S., Gregersen P. K., Harris C. C., Boyd J., Rennert G., Offit K. (2002). BLM heterozygosity and the risk of colorectal cancer. Science 297:2013. [*these authors made an equal contribution]
Foulkes W. D., Thiffault I., Gruber S. B., Horwitz M., Hamel N., Lee C., Shia J., Markowitz A., Figer A., Friedman E., Farber D., Greenwood C. M., Bonner J. D., Nafa K., Walsh T., Marcus V., Tomsho L., Gebert J., Macrae F. A., Gaff C. L., Paillerets B. B., Gregersen P. K., Weitzel J. N., Gordon P. H., MacNamara E., King M. C., Hampel H., De La Chapelle A., Boyd J., Offit K., Rennert G., Chong G., Ellis N. A. (2002). The founder mutation MSH2*1906G-->C is an important cause of hereditary nonpolyposis colorectal cancer in the Ashkenazi Jewish population. Am J Hum Genet 71:1395-412.
Eladad, S., Ye T.-Z., Hu P., Leversha M., Beresten S. F., Matunis M., Ellis N. A. (2005). Intra-nuclear trafficking of the BLM helicase to DNA damage induced foci is regulated by SUMO-1. Hum Mol Genet 14:1351-65.
Mitra N., Ye T.-Z., Smith A., Chuai S., Kirchhoff T., Peterlongo P., Nafa K., Phillips M. S., Offit K., Ellis N. A. (2004). Localization of cancer susceptibility genes by genome-wide SNP linkage disequilibrium mapping. Can Res 64:8116-25.
German J., Ellis N.A. (2002). Bloom syndrome. In: The Genetic Basis of Human Cancer Vogelstein B., Kinzler K., eds. New York: McGraw-Hill, Inc., pp. 267-88.
Gruber* S. B., Ellis* N. A., Scott K. K., Almog R., Kolachana P., Bonner J. D., Kirchhoff T., Tomsho L. P., Nafa K., Pierce H., Low M., Satagopan J., Rennert H., Huang H., Greenson J. K., Groden J., Rapaport B., Shia J., Johnson S., Gregersen P. K., Harris C. C., Boyd J., Rennert G., Offit K. (2002). BLM heterozygosity and the risk of colorectal cancer. Science 297:2013. [*these authors made an equal contribution]
Foulkes W. D., Thiffault I., Gruber S. B., Horwitz M., Hamel N., Lee C., Shia J., Markowitz A., Figer A., Friedman E., Farber D., Greenwood C. M., Bonner J. D., Nafa K., Walsh T., Marcus V., Tomsho L., Gebert J., Macrae F. A., Gaff C. L., Paillerets B. B., Gregersen P. K., Weitzel J. N., Gordon P. H., MacNamara E., King M. C., Hampel H., De La Chapelle A., Boyd J., Offit K., Rennert G., Chong G., Ellis N. A. (2002). The founder mutation MSH2*1906G-->C is an important cause of hereditary nonpolyposis colorectal cancer in the Ashkenazi Jewish population. Am J Hum Genet 71:1395-412.
