Ralf Krahe
Professor
The University of Texas MD Anderson Cancer Center
Department of Genetics
Research in my laboratory focuses on the identification and characterization of human rare disease genes, their mutations and underlying pathomechanisms, using classical genetics and molecular genetics, functional genomics and mechanism-based biology approaches, including hereditary cancer syndromes (Li-Fraumeni Syndrome, LFS) and neuromuscular disorders (myotonic dystrophies, DM).
LFS is a genetically heterogeneous, rare inherited cancer predisposition syndrome. Most cases are due to mutations in the tumor suppressor p53. We have mapped another LFS locus to chromosome 1q23 and are currently identifying the mutated gene. In p53 and non-p53 LFS, there is evidence for risk modifiers and factors in addition to the inherited susceptibility. To identify them, we are using integrated approaches combining omics approaches 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. Another focus is the molecular characterization of sporadic cancers that are part of the LFS tumor spectrum (sarcomas, brain, leukemia, lung, head and neck) by genome-wide genomic, epigenomic and transcriptomic approaches to identify changes underlying tumor initiation, progression and metastasis. A common underlying theme of my research is the application of state-of-the-art omics methodologies towards both discovery and translational goals.
Myotonic dystrophy, the most common adult neuromuscular disorder, is caused by mutant (CTG)DM1 or (CCTG)DM2 repeat expansions that when transcribed cause disease. It is unclear how these mutant toxic (CUG)DM1/(CCUG)DM2 RNAs mediate their disease-causing effects at the molecular and cellular level. To dissect their pathomechanisms, we are using functional genomics and molecular genetics approaches and have generated different transgenic, knock-in and knock-out mouse models.
Education & Training
PhD, MD Anderson UTHealth Houston Graduate School, 1995
Research Info
human and molecular genetics; familial cancer predisposition; cancer genomics; neurogenetics; mouse models