Research Group Genetic Alterations in Carcinogenesis
Dr. Monica Hollstein
Our goals are to understand the origins of tumor-specific genetic alterations, and to clarify the biological consequences of these changes. Elucidation of these points should assist in improving strategies for prevention, early detection,prognosis and treatment of cancer. Currently we are investigating various aspects of mutagenesis in the p53 tumor suppressor gene and other genes that control genetic stability and programmed cell death.
To test hypotheses on the causes of p53 mutations in human cancers, we have developed a mouse model (Hupki) in which we have replaced the endogenous murine p53 sequences with the human counterpart. This experimental tool can be used to address questions important both in molecular epidemiology and in the preclinical testing of novel drugs that target human tumor mutant p53 proteins. By means of oligonucleotide microarrays we also examine the biological effects of specific human transcription factor gene polymorphisms on the transcriptome of normal and stressed cells.