Ralf Krahe, Ph.D.
Present Title & Affiliation
Associate Professor, Department of Genetics, The University of Texas MD Anderson Cancer Center, Houston, TX
- Human and molecular genetics
- Cancer genetics
Research in the Krahe laboratory focuses on the identification and characterization of human disease genes and their mutations/variants, including inherited cancer syndromes (Li-Fraumeni Syndrome) and the myotonic dystrophies (DM), by classic and molecular genetics and genomics approaches.
Li-Fraumeni syndrome (LFS) is a genetically heterogeneous, rare inherited cancer syndrome. Most cases are due to mutations in the tumor suppressor p53. We have mapped a novel LFS predisposition locus to 1q23, the gene for which we are identifying. In p53 and non-p53 LFS, there is evidence for risk modifiers and factors inaddition to the inherited susceptibility. We are using integrated approaches combining genomic and epigenomic profiling to dissect the complex genetic and epigenetic events underlying LFS tumorigenesis. To dissect the pathophysiological consequences of variant genes, we are generating suitable LFS mouse models. LFS predisposition and/or modifier genes may also be functionally important in other tumor types lacking a clear genetic predisposition. The molecular characterization and classification of sporadic cancers (head and neck and lung cancer, and gliomas) through genomics methodologies to identify genomic, epigenomic and transcriptomic changes underlying tumor initiation, progression and metastasis is another focus.
Myotonic dystrophy, themost common adult neuromuscular disorder, is caused by mutant (CTG)DM1 or (CCTG)DM2 expansions that when transcribed cause disease. It is unclear how these mutant (CUG)DM1/(CCUG)DM2 RNAs mediate their disease-causing effects at the molecular and cellular level. To dissect the pathophysiology, we are using functional genomics and molecular genetics approaches and have generated transgenic, knock-in and knock-out mouse models.
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