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Jay
Tischfield, PhD |
| Title: Professor |
| Affiliation: Rutgers, The State University of NJ |
| Department:
Genetics |
| Research Interests:
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Primary research interests include studies of both somatically heritable and transient genetic changes in stem cells and somatic cells that predispose to disease in humans. Loss of heterozygosity (LOH) for tumor suppressor genes in somatic cells frequently results in a recessive cellular phenotype that leads to cancer. We have studied the frequency and mechanisms of LOH in human heterozygotes and produced a heterozygous mouse model for investigation of LOH in different genetic backgrounds and after exposure to environmental agents. We have discovered that the major mechanisms for LOH in normal somatic cells are mitotic recombination, followed by point mutation. Thus, we continue to investigate genes (e.g., Tp53, Mlh1, Msh2, Ku80) and environmental agents (e.g., ionizing radiation) that may affect these processes as well as the molecular biology of the processes. We are also investigating the role of interphase nuclear structure and repair complexes in different cell types with the aim of explaining differential rates of LOH in different types of cells. The mouse is an excellent model for this research due to the availability of many "knockouts" for genes that might affect LOH and our ability to deliver environmental agents, such as chemicals and radiation, in a precise manner. Our most recent work shows that mouse embryonic stem cells repair spontaneous and induced double strand breaks in DNA primarily by homologous recombination and that this can occur both before and after DNA replication. Repair before DNA replication uses the homologous chromosome as a template, thereby reducing the chances of LOH. In addition, we are engaged in several large projects whose ultimate goal is the identification of genes that have major contributions to complex oligogenic disorders such as alcoholism, autism and Tourette syndrome. |
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