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Ralf Krahe, Ph.D.

Present Title & Affiliation

Primary Appointment

Associate Professor, Department of Genetics, University of Texas M. D. Anderson Cancer Center, Houston, TX

Research Interests

  • Human and molecular genetics
  • Neurogenetics
  • Cancer genetics
  • Genomics

Research in the Krahe laboratory is targeted toward the identification and characterization of the human genes and their mutations that underlie several inherited Mendelian and multi-factorial diseases, using classic genetic and molecular genetic approaches. These include neuromuscular disorders (myotonic dystrophies, DM1, DM2 and DMx) as well as inherited cancers, such as Li-Fraumeni syndrome (LFS).

DM1 and DM2 are caused by the mutant expansion of unstable (CTG)n and (CCTG)n microsatellite repeats. These repeats need to be transcribed to cause disease and accumulate in ribonuclear inclusions; thus, DM1 and DM2 can be considered RNA diseases. However, it remains unclear how exactly these mutant RNAs mediate their disease-causing effects at the molecular and cellular level. To dissect the underlying pathophysiology, we are using a variety of functional genomics approaches and are generating different mouse models. There also is evidence for additional genetic heterogeneity (DMx), and we are positionally cloning at least one other gene for DM.

LFS is a clinically and genetically heterogeneous inherited cancer syndrome. Most cases are due to mutations in the tumor suppressor gene p53. We recently mapped another LFS locus to 1q23, which we are positionally cloning. In both p53 and non-p53 LFS, there is evidence for risk heterogeneity within and between kindreds, suggesting other risk modifiers and factors, including epigenetic alterations in addition to the inherited susceptibility. We are using an integrated genomics approach combining genomic and transcriptomic with epigenomic profiling to gain a better understanding of the complex molecular genetic and epigenetic events underlying the multistep carcinogenesis in LFS. As a childhood cancer, LFS is a unique model to study the underlying genetic events associated with a complex cancer syndrome, presumably because fewer such alterations are needed to give rise to the associated cancer. LFS predisposition and/or modifier genes may also be functionally important in other solid tumor types lacking a clear predisposition and inheritance pattern.

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. A common underlying theme is the use of the tools developed by the human genome project.

Depending on the student's interests, a tutorial in my laboratory would provide experience with positional cloning, including genetic linkage analysis, DNA microarray technologies, genomics and bioinformatics in the areas of neurogenetics and cancer genetics.

Office Address

Phone: (713) 834-6345
Email: RKrahe@mdanderson.org

Education & Training

Degree-Granting Education

1995 University of Texas Health Science Center, Houston, TX, PHD, Biomedical Sciences with emphasis in Genetics
1988 University of Arkansas, Fayetteville, AR, BS, Magna Cum Laude, Microbiology

Selected Publications

Peer-Reviewed Original Research Articles
1. Aminoff M, Carter JE, Chadwick RB, Johnson C, Grasbeck R, Abdelaal MA, Broch H, Jenner LB, Verroust PJ, Moestrup SK, de la Chapelle A, Krahe R. Mutations in CUBN, encoding the intrinsic factor-vitamin B12 receptor, cubilin, cause hereditary megaloblastic anaemia 1. Nat Genet 21:309-13, 3/1999. PMID: 10080186.
2. Virtaneva K, Wright FA, Tanner SM, Yuan B, Lemon WJ, Caligiuri MA, Bloomfield CD, de La Chapelle A, Krahe R. Gene expression profiling reveals fundamental biological differences in acute myeloid leukemia with isolated trisomy 8 and normal cytogenetics. Proc Natl Acad Sci U S A 98:1124-9, 1/2001. PMID: 11158605.
3. Wright FA, Lemon WJ, Zhao WD, Sears R, Zhuo D, Wang JP, Yang HY, Baer T, Stredney D, Spitzner J, Stutz A, Krahe R, Yuan B. A draft annotation and overview of the human genome. Genome Biol 2:RESEARCH0025, 2001. PMID: 11516338.
4. Zhang S, Krahe R. Physical and transcript map of a 2-Mb region in Xp22.1 containing candidate genes for X-linked mental retardation and short stature. Genomics 79:274-7, 3/2002. PMID: 11863356.
5. Colella S, Shen L, Baggerly KA, Issa JP, Krahe R. Sensitive and quantitative universal Pyrosequencing methylation analysis of CpG sites. Biotechniques 35:146-50, 7/2003. PMID: 12866414.
6. Bachinski LL, Udd B, Meola G, Sansone V, Bassez G, Eymard B, Thornton CA, Moxley RT, Harper PS, Rogers MT, Jurkat-Rott K, Lehmann-Horn F, Wieser T, Gamez J, Navarro C, Bottani A, Kohler A, Shriver MD, Sallinen R, Wessman M, Zhang S, Wright FA, Krahe R. Confirmation of the type 2 myotonic dystrophy (CCTG)n expansion mutation in patients with proximal myotonic myopathy/proximal myotonic dystrophy of different European origins: a single shared haplotype indicates an ancestral founder effect. Am J Hum Genet 73:835-48, 10/2003. PMID: 12970845.
7. Sallinen R, Vihola A, Bachinski LL, Huoponen K, Haapasalo H, Hackman P, Zhang S, Sirito M, Kalimo H, Meola G, Horelli-Kuitunen N, Wessman M, Krahe R, Udd B. New methods for molecular diagnosis and demonstration of the (CCTG)n mutation in myotonic dystrophy type 2 (DM2). Neuromuscul Disord 14:274-83, 4/2004. PMID: 15019706.
8. Bachinski LL, Olufemi SE, Zhou X, Wu CC, Yip L, Shete S, Lozano G, Amos CI, Strong LC, Krahe R. Genetic mapping of a third Li-Fraumeni syndrome predisposition locus to human chromosome 1q23. Cancer Res 65:427-31, 1/2005. PMID: 15695383.

Last updated: 5/18/2009