Changshun Shao
Assistant Research Professor

Genetic. epigenetic and environmental factors in the genesis of somatic mutation

I am interested in somatic cell mutation in vivo and its role in the pathogenesis of diseases such as cancer. Mutations in somatic cells are known to drive the initiation and the progression of cancer. However. the mechanisms by which mutations are generated and accumulated in vivo remains to be determined. We study factors that modulate the levels of somatic mutations or tumor incidence by using mouse models. Our study of mutations that arise in mice with various genetic defects has yielded invaluable insights into how somatic mutations are prevented or reduced under normal conditions. We are currently examining factors that are involved in DNA repair. chromatin modification and cell survival.

Selected Publications

Barrera-Oro J, Liu TY, Gorden E, Kucherlapati R, Shao C, Tischfield JA. (2008) Role of the mismatch repair gene, Msh6, in suppressing genome instability and radiation-induced mutations. Mutat Res. 642(1-2):74-9.

Liang L, Deng L, Nguyen SC, Zhao X, Maulion CD, Shao C, Tischfield JA. (2008) Human DNA ligases I and III, but not ligase IV, are required for microhomology-mediated end joining of DNA double-strand breaks. Nucleic Acids Res. 36(10):3297-310.

Liang L, Deng L, Mendonca MS, Chen Y, Zheng B, Stambrook PJ, Shao C, Tischfield JA. (2007) X-rays induce distinct patterns of somatic mutation in fetal versus adult hematopoietic cells. DNA Repair (Amst). 6(9):1380-5.

Zhu G, Ke X, Liu Q, Li J, Chen B, Shao C, Gong Y. (2007) Recurrence of the D100N mutation in a Chinese family with brachydactyly type A1: Evidence for a mutational hot spot in the Indian hedgehog gene. Am J Med Genet A. 143A(11):1246-8.

Liang L, Mendonca MS, Deng L, Nguyen SC, Shao C, Tischfield JA. (2007) Reduced apoptosis and increased deletion mutations at Aprt locus in vivo in mice exposed to repeated ionizing radiation. Cancer Res. 67(5):1910-7.

Zou Y, Liu Q, Chen B, Zhang X, Guo C, Zhou H, Li J, Gao G, Guo Y, Yan C, Wei J, Shao C, Gong Y. (2007) Mutation in CUL4B, which encodes a member of cullin-RING ubiquitin ligase complex, causes X-linked mental retardation. Am J Hum Genet. 80(3):561-6.

Liang L. Deng L. Chen Y. Li GC. Shao C. Tischfield JA. (2005) Modulation of DNA end joining by nuclear proteins. J Biol Chem. 280(36):31442-9.

Shao C. Deng L. Chen Y. Kucherlapati R. Stambrook PJ. Tischfield JA. (2004). Mlh1 mediates tissue-specific regulation of mitotic recombination. Oncogene (in press).

Tischfield JA. Shao C. (2003). Somatic recombination redux. Nature Genetics 33: 5-6.

Cervantes RB. Stringer JR. Shao C. Tischfield JA. Stambrook PJ. (2002). Embryonic stem cells and somatic cells differ in mutation frequency and type. Proc. Natl. Acad. Sci. USA 99: 3586-3590.

Shao C. Yin M. Deng L. Stambrook PJ. Doetschman T. Tischfield JA. (2002). Loss of heterozygosity and point mutation at Aprt locus in T cells and fibroblasts of Pms2-/- mice. Oncogene 21:2840-2845.

Shao C. Stambrook PJ. Tischfield JA. (2001). Mitotic recombination is suppressed by chromosomal divergence in hybrids of distantly related mouse strains. Nature Genetics 28:169-172.

Shao C. Deng L. Henegariu O. Liang L. Stambrook PJ. Tischfield JA. (2000). Chromosome instability contributes to loss of heterozygosity in mice lacking p53. Proc. Natl. Acad. Sci. USA 97:7405-7410.