Accessibility Navigation:


Banner
Richardson, Christine, Ph.D.

Associate Professorrichardson-christine

DNA Repair, Chromosomal Rearrangements, & Hematopoietic Malignancies.

Phone, Office: 704.687.8683
Phone, Lab: 704.687.8683
Office: Woodward 386B
Email:

Research Interests

Etiology of DNA damage-induced chromosomal rearrangements common to leukemias, lymphomas, and soft-tissue sarcomas. The long-term objective of my research is to understand the mechanisms used by hematopoietic cells to repair of one type of DNA damage -- the double-strand break (DSB)-- and the initial molecular events that lead to genomic rearrangements such as translocations, which are a hallmark of leukemias, lymphomas, and soft-tissue sarcomas. Radiation and DNA damaging agents are common therapy in the treatment of human cancers. Exposure to these agents also leads to chromosomal DSBs that may be aberrantly repaired to produce rearrangements and oncogenic transformation and tumor formation. Recent data from my lab indicates that chromosomal rearrangements analogous to those observed in hematopoietic malignancies are readily formed during DSB repair in both human and mouse hematopoietic stem cell-enriched populations. However, the majority of these rearrangements are not sufficient for malignant progression. My lab uses multiple genetic approaches in cultured cell lines and genestically engineered mice to identify the initial events that promote the formation of DNA damage-induced chromosomal rearrangements, and the cooperative mutations or predisposing factors that can promote (or suppress) transformation of cells that acquire them. This research will provide an understanding of the earliest events in DNA repair and the development of certain tumors, particularly therapy-related and infant leukemia, and may lead to new approaches to therapy and prevention.

Professional Experience

  • Post-doctoral Fellow; Department of Cell Biology and Genetics, Sloan-Kettering Institute, NY (1995-1999)
  • Research Associate; Department of Cell Biology and Genetics, Sloan-Kettering Institute, NY (1999-2001)
  • Assistant Professor; Institute for Cancer Genetics, Department of Pathology, Columbia University, NY (2001-2005)
  • Associate Professor; Department of Biology, Bioinformatics Research Center, UNC Charlotte, NC (2006- )

Education

  • A.B., Department of Molecular Biology, Princeton University (1990)
  • Ph.D., Department of Genetics & Development, Columbia University (1995)

Courses Taught

  • Cancer Genetics (6000/8000)
  • Molecular Biology (4199/5199)
  • Cell Biology (3111)

Selected Publications

  • Richardson, C., Moynahan, M., Jasin, M. Double-strand break repair by interchromosomal recombination: Suppression of chromosomal translocations. Genes & Dev. 12:3831-3842, 1998.
  • Richardson, C., and Jasin, M. Frequent chromosomal translocations induced by DNA double-strand breaks. Nature 405: 697-700, 2000.
  • Richardson, C., and Jasin, M. Coupled homologous and nonhomologous repair of a double-strand break preserves genomic integrity in mammalian cells. Mol. Cell. Biol. 20: 9068-9075, 2000.
  • Elliott, B., Richardson, C., Jasin, M. Chromosomal translocation mechanisms at intronic alu elements in mammalian cells. Mol. Cell 17: 885-894, 2005.
  • Richardson, C. , Stark, J., Ommundsen, M., Jasin, M. Over-expression of Rad51 promotes alternative DSB repair and genome instability. Oncogene 23: 546-553, 2004.
  • Richardson, C., Horikoshi, N., and Pandita, T. The DSB response network in meiosis. DNA Repair 3: 1149-1164, 2004.
  • Richardson, C. Rad51, genomic stability, and tumorigenesis. Cancer Letters 218: 127-139, 2005.
  • Libura, J., Slater, D.J., Felix, C.A., Richardson, C. t-AML-like MLL Rearrangements are induced by etoposide in primary human CD34+ cells and remain stable after clonal expansion. Blood 105: 2124-2131, 2005.
  • Pulte, D., Lopez, R.A., Baker, S.T., Ward, M., Ritchie, E., Richardson, C., O'Neill, D.W., Bank, A. Ikaros increases normal apoptosis of adult erythroid cells. Amer J Hem 81: 12-17, 2006.
  • Weinstock, D., Elliott, B., Richardson, C., Jasin, M. Modeling oncogenic translocations: Distinct roles for double-strand break repair pathways in translocation formation in mammalian cells. DNA Repair, 5: 1065-1074, 2006.
  • Sung, P.A., Libura, J., Richardson, C. Etoposide and illegitimate DNA double-strand break repair in the generation of MLL chromosomal translocations. DNA Repair, 5: 1109-1118, 2006.
  • Felix, C., Robinson, B., Germano, G., Kolaris, C., Raffini, L., Nigro, L., Roumm,. E., Megonigal, M., Slater, D., Whitmarsh, R., Saginario, C., Lovett, B., Libura, J., Pegram, L., Zheng, N., Pang, S., Zhou, X., Rappaport, E., Richardson, C., Cheung, N., Blair, I., Osheroff, N. Translocation mechanism in secondary leukemias following topoisomerase II poison. In Proceedings of the Third International Symposium on Secondary Leukemias. Rome, Italy: 2006.
  • Angevine A., McCafferty, J, Bhagat, G, Friedman, R, Vogel, S, Bank, A, Richardson, C., Mears, J. Differential Gene Expression in Nodular Sclerosis Hodgkin s Lymphoma: Revealing the role of cells in the microenvironment in disease pathogenesis. Blood, 11(108A), 2006 .
  • Mantha, S., Ward, M., McCafferty, J., Herron, A., Palomero, T., Ferrando, A., Bank, A., Richardson, C. Activating Notch1 mutations are an early event in T-cell malignancy of Ikaros point mutant Plastic /+ mice. Leuk Res, 31(3): 321-327, 2007.
  • Francis, R. and Richardson, C. Hematopoietic multipotent progenitor cells highly susceptible to alternative double-strand break repair pathways that promote genome rearrangements. Genes & Dev, 2007.
  • Koptyra, M., Cramer, K., Richardson, C., Skorski, T. BCR/ABL promotes accumulation of chromosomal aberrations after oxidative and genotoxic stress. Leukemia, 22(10): 1969-1972, 2008.
  • Libura, J., Ward, M., Solecka, J., Richardson, C. Etoposide initiated MLL rearrangements detected at high frequency in primitive hematopoietic stem cells with in vitro and in vivo long term repopulating potential. Eur J Hem, 81(3): 185-195, 2008.
  •  Pandita, T.K. and Richardson, C. Chromatin remodeling finds its place in the DNA double-strand break response. Nucleic Acid Res, Jan 12 2009.
  • Mouzannar, R., McCafferty, J., Benedetto, G., Richardson, C. Low dose and high dose oxidative stress elicit early genomic and phospho-proteomic cellular responses that provide insight into cellular transformation. 2009.