Meet Ralf Krahe, Ph.D.
Ralf Krahe, Ph.D.
Department of Genetics, Division of VP, Research
About Dr. Krahe
Dr. Krahe is a Professor in the Department of Genetics. His laboratory focuses on the identification and characterization of human rare disease genes, their mutations and underlying pathomechanisms that underlie several Mendelian diseases, using classical genetics and molecular genetics, functional genomics and mechanism-based biology approaches, including mouse and fly models. Diseases include hereditary cancer syndromes (Li-Fraumeni Syndrome and its variants, LFS /LFL ) and neuromuscular disorders (myotonic dystrophies, DM). Another focus has been the molecular characterization of sporadic cancers that are part of the LFS tumor spectrum (sarcomas, brain, leukemia, lung, head and neck) by genome-wide approaches to identify genomic, epigenomic and transcriptomic changes underlying tumor initiation, progression and metastasis. A common underlying theme of his research is the application of state-of-the-art omics methodologies towards both discovery and translational goals. In addition, Dr. Krahe is active in efforts that promote graduate and postdoctoral training and mentoring.
Visit Dr. Krahe's Lab website.
View a complete list of Dr. Krahe's publications.
Present Title & Affiliation
Professor (tenured), Department of Genetics, Division of Basic Science Research, University of Texas MD Anderson Cancer Center, Houston, TX
Professor, University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences, Houston, TX
Human & molecular genetics | Cancer genetics | Neurogenetics | Genomics | Animals models
Research in the Krahe laboratory focuses on the identification and characterization of human rare disease genes, their mutations and underlying pathomechanisms that underlie several Mendelian diseases, using classical genetics and molecular genetics, functional genomics and mechanism-based biology approaches, including mouse and fly models. Diseases include hereditary cancer syndromes (Li-Fraumeni Syndrome and its variants, LFS/LFL) and neuromuscular disorders (myotonic dystrophies, DM).on the identification and characterization of human disease genes and their mutations and 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 gene TP53 (p53). We previously mapped a novel LFS/LFL predisposition locus to chromosome 1q23 and have recently identified a novel mutated tumor suppressor gene I multiple non-p53 LFS/LFL families. In both p53 and non-p53 LFS, there is additional evidence for risk modifiers and factors in addition 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 (sarcomas, brain, leukemia, lung, head and neck) through genomics methodologies to identify genomic, epigenomic and transcriptomic changes underlying tumor initiation, progression and metastasis has been another focus.
Myotonic dystrophy, the most common adult neuromuscular disorder, is caused by mutant (CTG) DM1 or (CCTG) DM2 repeat expansion mutations that when transcribed cause disease. It is currently 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 and fly models.
Visit Dr. Krahe's Lab website.
View a complete list of Dr. Krahe's publications.
Education & Training
|1995||University of Texas MD Anderson Cancer Center, UTHealth Graduate School of Biomedical Sciences (GSBS), Houston, TX, USA, PHD, Biomedical Sciences with emphasis in Genetics; thesis research mentor Michael J. Siciliano, PhD|
|1988||University of Arkansas, Fayetteville, AR, USA, BS, Microbiology; honors thesis research mentor Timothy A. Kral, PhD|
|1995-1996||Postdoctoral Fellow, Molecular Genetics, Department of Medical Genetics, University of Helsinki, Helsinki|
Honors & Awards
|2019||President’s Recognition of Faculty Excellence Award for Education & Mentorship Advancement, University of Texas MD Anderson Cancer Center|
|2019||Deans’ Recognition for Outstanding Contributions towards Graduate Education, University of Texas MD Anderson Cancer Center, UTHealth Graduate School of Biomedical Sciences, Houston, TX|
|2018||Faculty Educator of the Month, for significant contribution to teaching excellence, University of Texas MD Anderson Cancer Center|
|2017||Professor, Reappointment with Commendation, University of Texas MD Anderson Cancer Center, UTHealth Graduate School of Biomedical Sciences, Houston, TX|
|2016||Barbara Bowman Distinguished Texas Geneticist Award, for outstanding contributions to genetics in Texas, Texas Genetics Society|
|2014||Commencement Hooder, University of Texas MD Anderson Cancer Center, UTHealth Graduate School of Biomedical Sciences, Houston, TX|
|2012||Professor, Reappointment with Commendation, University of Texas MD Anderson Cancer Center, UTHealth Graduate School of Biomedical Sciences, Houston, TX|
|2007||Associate Professor, Reappointment with Commendation, University of Texas MD Anderson Cancer Center, UTHealth Graduate School of Biomedical Sciences, Houston, TX|
|2002||Distinguished Alumnus, Human & Molecular Genetics Graduate Program, University of Texas MD Anderson Cancer Center, UTHealth Graduate School of Biomedical Sciences, Houston, TX|
|1997||Molecular Life Sciences Scholar - Molecular Medicine, Ohio State University|
|1997||European Union Marie-Curie Fellow, Helsinki, Finland|
|1997||Sigrid Juselius Foundation Fellow, Helsinki, Finland|
|1988||B.S. magna cum laude, University of Arkansas|
- Morales F, Corrales E, Zhang B, Vásquez M, Santamaría-Ulloa C, Quesada H, Sirito M, Estecio MR, Monckton DG, Krahe R. Myotonic dystrophy type 1 (DM1) clinical subtypes and CTCF site methylation status flanking the CTG expansion are mutant allele length-dependent. Hum Mol Genet 31(2):262-274, 2021. PMID: 34432028.
- Morales F, Vásquez M, Corrales E, Vindas-Smith R, Santamaría-Ulloa C, Zhang B, Sirito M, Estecio MR, Krahe R, Monckton DG. Longitudinal increases in somatic mosaicism of the expanded CTG repeat in myotonic dystrophy type 1 are associated with variation in age-at-onset. Hum Mol Genet 29(15):2496-2507, 2020. PMID: 32601694.
- Kurkiewicz A, Cooper A, McIlwaine E, Cumming SA, Adam B, Krahe R, Puymirat J, Schoser B, Timchenko L, Ashizawa T, Thornton CA, Rogers S, McClure JD, Monckton DG. Towards development of a statistical framework to evaluate myotonic dystrophy type 1 mRNA biomarkers in the context of a clinical trial. PLoS One 14(15(4)):e0231000. doi: 10.1371/journal.pone.0231000. eCollection 2020, 2020. e-Pub 2020. PMID: 32287265.
- Schoser B, Montagnese F, Bassez G, Fossati B, Gamez J, Heatwole C, Hilbert J, Kornblum C, Kostera-Pruszczyk A, Krahe R, Lusakowska A, Meola G, Moxley R, Thornton C, Udd B, Formaker P, Myotonic Dystrophy Foundation. Consensus-Based Care Recommendations for Myotonic Dystrophy Type 2. Neurol Clin Pract 9(4):343-353, 2019. PMID: 31583190.
- Corrales E, Vásquez M, Zhang B, Santamaría-Ulloa C, Cuenca P, Krahe R, Monckton DG, Morales F.. Analysis of mutational dynamics at the DMPK (CTG)n locus identifies saliva as a suitable sample source for genetic analysis in myotonic dystrophy type 1. PLoS One 14(5), 2019. PMID: 31048891.
- Larsson C, Moyer S, Liu B, Michel K, Pant V, Yang P, Wong J, El-Naggar A, Krahe R, Lozano G. Retinoid-induced RARγ activation enhances the therapeutic response to p53 restoration in a mouse model of Li Fraumeni syndrome. Proc Natl Acaad Sci USA 115(9):21982203, 2018. PMID: 29440484.
- Qian DC, Molfese DL, Jin JL, Titus AJ, He Y, Li Y, Vaissié M, Viswanath H, Baldwin PR, Krahe R, Salas R, Amos CI. Genome-wide imaging association study implicates functional activity and glial homeostasis of the caudate in smoking addiction. BMC Genomics 18(1):740, 2017. PMID: 28927378.
- Yenigun VB, Sirito M, Amcheslavky A, Czernuszewicz T, Colonques-Bellmunt J, García-Alcover I, Wojciechowska M, Bolduc C, Chen Z, López Castel A, Krahe R, Bergmann A. (CCUG)n RNA toxicity in a Drosophila model of myotonic dystrophy type 2 (DM2) activates apoptosis. Dis Model Mech 10(8):993-1003, 2017. PMID: 28623239.
- Chakraborty S, Vatta M, Bachinski LL, Krahe R, Dlouhy S, Bai S. Molecular Diagnosis of Myotonic Dystrophy. Curr Protoc Hum Genet 91:9 29 21-29 29 19, 2016. PMID: 27727437.
- Chen Q, Sinha K, Deng JM, Yasuda H, Krahe R, Behringer RR, de Crombrugghe B. Mesenchymal Deletion of Histone Demethylase NO66 in Mice Promotes Bone Formation. J Bone Mineral Res 30(9):1608-17, 2015. e-Pub 2015. PMID: 25736226.
- Chen Q, Zhang L, de Crombrugghe B, Krahe R. Mesenchyme-specific overexpression of nucleolar protein 66 in mice inhibits skeletal growth and bone formation. FASEB J 29(6):2555-65, 2015. e-Pub 2015. PMID: 25746793.
- Screen M, Jonson PH, Raheem O, Laaksonen R, Lehtimaki T, Sirito M, Krahe R, Hackman P, Udd B.. Abnormal splicing of NEDD4 in myotonic dystrophy type 2: a possible link to statin adverse reactions. Am J Pathol 184(8):2322-32, 2014. PMID: 24907641.
- Bachinski LL, Baggerly KA, Neubauer VL, Nixon TJ, Raheem O, Sirito M, Unruh AK, Zhang J, Nagarajan L, Timchenko LT, Bassez G, Eymard B, Gamez J, Ashizawa T, Mendell JR, Udd B, Krahe R. Most expression and splicing changes in myotonic dystrophy type 1 and type 2 skeletal muscle are shared with other muscular dystrophies. Neuromuscul Disord 24(3):227-40, 2014. e-Pub 2013. PMID: 24332166.
- Vihola A*, Sirito M, Bachinski L, Raheem O, Suominen T, Krahe R* and Udd B. Aberrant expression and splicing of Ca2+ metabolism genes in myotonic dystrophies DM1 and DM2. Neuropathol Applied Neurobiol (*corresponding authors) 39(4):390-405, 2013. e-Pub 2012.
- Udd B*, and Krahe R*. The myotonic dystrophies: clinical, molecular and therapeutic challenges. Lancet Neurol (*corresponding authors) 11(10):891-905, 2012.
- Suominen T, Bachinski LL, Auvinen S, Hackman P, Baggerly KA, Angelini C, Peltonen L, Krahe R, Udd B.. Population frequency of myotonic dystrophy: higher than expected frequency of myotonic dystrophy type 2 (DM2) mutation in Finland. Eur J Hum Genet 19(7):776-82, 2011. e-Pub 2011.
- Udd B, Meola G, Krahe R, Wansink DG, Bassez G, Kress W, Schoser B, Moxley R. Myotonic dystrophy type 2 (DM2) and related disorders report of the 180th ENMC workshop including guidelines on diagnostics and management 3-5 December 2010, Naarden, The Netherlands. Neuromuscul Disord 21(6):443-50, 2011. e-Pub 2011. PMID: 21543227.
- Wu CC, Krahe R, Lozano G, Zhang B, Wilson CD, Jo EJ, Amos CI, Shete S, Strong LC. Joint effects of germ-line TP53 mutation, MDM2 SNP309, and gender on cancer risk in family studies of Li-Fraumeni syndrome. Hum Genet 129(6):663-73, 2011. e-Pub 2011. PMID: 21305319.
- Raheem O, Olufemi SE, Bachinski LL, Vihola A, Sirito M, Holmlund-Hampf J, Haapasalo H, Li YP, Udd B, Krahe R. Mutant (CCTG)n Expansion Causes Abnormal Expression of Zinc Finger Protein 9 in Myotonic Dystrophy Type 2. Am J Pathol 177(6):3025-36, 2010. e-Pub 2010.
- Richards KL, Zhang B, Sun M, Dong W, Churchill J, Bachinski LL, Wilson CD, Baggerly KA, Yin G, Hayes DN, Wistuba II, Krahe R. Methylation of the candidate biomarker TCF21 is very frequent across a spectrum of early stage non-small cell lung cancers. Cancer 117(3):606-617. e-Pub 2010.
- Cheung HC, Hai T, Zhu W, Baggerly KA, Tsavachidis S, Krahe R, Cote GJ. Splicing factors PTBP1 and PTBP2 promote proliferation and migration of glioma cell lines. Brain 132(Pt 8):2277-88, 2009. e-Pub 2009. PMID: 19506066.
- Bachinski LL, Czernuszewicz T, Ramagli LS, Suominen T, Shriver MD, Udd B, Siciliano MJ, Krahe R. Pre-mutation allele pool in myotonic dystrophy type 2. Neurology (*highlighted in accompanying editorial) 72(6):490-7, 2009. e-Pub 2008. PMID: 19020295.
- Richards KL, Zhang B, Baggerly KA, Colella S, Lang JC, Schuller DE, Krahe R. Genome-wide hypomethylation in head and neck cancer is more pronounced in HPV-negative tumors and is associated with genomic instability. PLoS One 4(3):e4941, 2009. e-Pub 2009. PMID: 19293934.
- Colella S, Richards KL, Bachinski LL, Baggerly KA, Tsavachidis S, Lang JC, Schuller DE, Krahe R. Molecular signatures of metastasis in head and neck cancer. Head Neck (Cover Illustration*) 30(10):1273-83, 2008. PMID: 18642293.
- Cheung HC, Baggerly KA, Tsavachidis S, Bachinski LL, Neubauer VL, Nixon TJ, Aldape KD, Cote GJ, Krahe R. Global analysis of aberrant pre-mRNA splicing in glioblastoma using exon expression arrays. BMC Genomics 9:216, 2008. PMID: 18474104.
- 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(2):427-31, 2005. PMID: 15695383.
- 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(4):835-48, 2003. PMID: 12970845.
- Krahe R, Zhang B, Hu X, Wong JW,Wilson CD,Baggerly KA, Navin NE, Strong LC, and Bachinski LL. Integrated genomic and epigenomic profiling of TP53 and non-TP53 Li-Fraumeni syndrome (LFS) tumors reveals multiple and shared hits in the p53 network. Platform presentation at the Annual European Society of Human Genetics Meeting, Nuremberg, Germany, 2012.