faculty risch(final) 2013 - heidelberg university · curriculum(vitae(1988 - 92(ba (hons),...
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Faculty
Angela Risch, D. Phil.
Research Interests
Epigenomic variation in airway diseases Molecular and epigenetic epidemiology of lung cancer Epi-‐Gene-‐ Environment Interaction in airway diseases
Pharmacoepigenetics
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Short CV Affiliation Angela Risch Group Leader: Lung Cancer Genomics/Epigenomics Div. Epigenomics & Cancer Risk Factors (C010) DKFZ German Cancer Research Center Im Neuenheimer Feld 280 D-‐ 69120 Heidelberg phone: +49 6221-‐ 424322 e-‐mail: [email protected] homepage: http://www.dkfz.de/en/tox/lung_cancer_genomics_epigenomics-‐neu.html Curriculum Vitae 1988 - 92 BA (hons), Biochemistry, University of Oxford, UK 1995 D.Phil. Phys Sciences, University of Oxford, Dept. Pharmacology, UK 1996 - 98 Postdoc in the Division of Toxicology and Cancer Risk Factors (head Prof. Helmut
Bartsch), DKFZ
1998 - 07 Research Scientist, Division of Toxicology and Cancer Risk Factors, DKFZ 2004 Habilitation and Venia Legendi in Molecular Toxicology at the Medical Faculty of
Heidelberg University
Since 2007 Group Leader ‘Epigenetics and Genetics of Lung Cancer’ in the Division of ‘Epigenomics and Cancer Risk Factors’ (head Prof. Christoph Plass), DKFZ
2009-12 Elected Steering Committee member of the International Lung Cancer Consortium (http://ilcco.iarc.fr/)
Honours & Awards 1992-95 Scholarship from Christopher Welch Trust, Oxford University
1997-98 ‘DFG-Forschungsstipendium’ – research stipend
2004 Dr. Emil Salzer Preis for Cancer Research in Baden Württemberg 2004
Projects § Epigenetic markers for lung cancer risk prediction and early detection Lung cancer prognosis and survival can be substantially improved by early detection. For optimal balance of potential benefits versus financial costs and possible health hazards of screening, screening must be targeted to individuals with high absolute lung cancer risk. To identify candidate epigenetic lung cancer risk markers, comparative genome wide methylation screening will be performed to identify CpG sites differentially methylated in existing blood samples from lung cancer cases and control subjects as well as in lung tumour vs. adjacent normal tissue in LC-‐2. Genome screens will use MCIp enrichment followed by array-‐based or NGS analysis. § Epigenetic programming of CF lung disease This project on epigenetic programming of the diversity of pulmonary disease in monozygous CF twins will test the hypothesis whether postnatal exposure to inanimate and animate irritants leads to somatic mutations and epigenetic imprints in airway epithelial and immune effector cells that substantially shape the progression of pulmonary disease in CF.
§ Methylation analysis of lung cancer susceptibility loci Within an NIH-‐funded project “Transdisciplinary Research into Cancer of the Lung (TRICL), we are investigating lung cancer susceptibility loci for interindividual variation in methylation, aberrant methylation in tumor vs normal tissues, and epigenetic regulation at these loci. Funding DZL – BMBF
National Institutes of Health (NIH), USA (http://epi.grants.cancer.gov/gameon/) Deutsche Krebshilfe Team Senior Scientists Prof. Dr. Wolfgang Hagmann Tel: +49 (0) 6221 424320 Email: [email protected] Dr. Svitlana Melnik Tel: +49 (0) 6221 424332 Email: [email protected] PhD students Hanna Jacobsson Email: [email protected] Christian Faltus E.mail: [email protected] M.D. Students Satenik Harutyunova Email: Satenik.Harutyunova@thoraxklinik-‐heidelberg.de Technical Assistants Marion Bähr Tel.: +49 (0)6221 423221 Email: [email protected]
Selected Publications Scherf D.B., Sarkisyan N., Jacobsson H., Claus R., Bermejo J.L., Gu L., Muley T., Meister M., Dienemann H., Plass C., Risch A. (2012) Epigenetic screen identifies genotype-‐ specific promoter DNA methylation and oncogenic potential of CHRNB4. Oncogene, 2012 Sep 3. doi: 10.1038/onc.2012.344. [Epub ahead of print] Campa D, Müller P, Edler L, Knoefel L, Barale R, Heussel CP, Thomas M, Canzian F, Risch A. (2012) A comprehensive study of polymorphisms in ABCB1, ABCC2 and ABCG2 and lung cancer chemotherapy response and prognosis.(2012) Int J Cancer 131(12):2920-‐8. Timofeeva MN, Hung RJ, Rafnar T, Christiani DC, Field JK, Bickeboller H, Risch A, McKay JD, Wang Y, Dai J, Gaborieau V, McLaughlin J, Brenner D, Narod S, Caporaso NE, Albanes D, Thun M, Eisen T, Wichmann HE, Rosenberger A, Han Y, Chen W, Zhu D, Spitz M, Wu X, Pande M, Zhao Y, Zaridze D, Szeszenia-‐Dabrowska N, Lissowska J, Rudnai P, Fabianova E, Mates D, Bencko V, Foretova L, Janout V, Krokan HE, Gabrielsen ME, Skorpen F, Vatten L, Njølstad I, Chen C, Goodman G, Lathrop M, Benhamou S, Vooder T, Välk K, Nelis M, Metspalu A, Raji O, Chen Y, Gosney J, Liloglou T, Muley T, Dienemann H, Thorleifsson G, Shen H, Stefansson K, Brennan P, Amos CI, Houlston R, Landi MT; for TRICL Research Team. Influence of Common Genetic Variation on Lung Cancer Risk: Meta-‐Analysis of 14,900 Cases and 29,485 Controls. (2012) Hum Mol Genet. 21(22):4980-‐95. Knöfel L.F, Werle-‐Schneider G., Dally H., Müller P.J., Edler L., Bartsch H., Tuengerthal S., Heussel C.P., Reinmuth N., Thomas M., Risch A. (2011) Polymorphisms in the apoptotic pathway gene BCL-‐2 and survival in small cell lung cancer. Journal of Thoracic Oncology, 6:183-‐189. Truong T., Hung R. J., Amos C. I., Wu X., Bickeböller H., Rosenberger A., Sauter W., Illig T., Wichmann H.-‐E., Risch A., Dienemann H., Kaaks R., Yang P., Jiang R., Wiencke J. K., Wrensch M., Hansen H., Kelsey K. T., Matsuo K., Tajima K., Schwartz A. G., Wenzlaff A., Seow A., Ying C., Staratschek-‐Jox A., Nürnberg P., Stoelben E., Wolf J., Lazarus P., Muscat J. E., Gallagher C., Zienolddiny S., Haugen A., van der Heijden H. F. M., Kiemeney L. A., Isla D., Mayordomo J. I., Rafnar T., Stefansson K., Zhang Z.-‐F., Chang S.-‐C., Kim J. H., Hong Y.-‐C., Duell E. J., Andrew A. S., Lejbkowicz F., Rennert G., Müller H., Brenner H., Le Marchand L., Benhamou S., Bouchardy C., Teare M. D., Xue Xi., McLaughlin J., Liu G., McKay J. D., Brennan P., Spitz M. (2010) Replication of Lung Cancer Susceptibility Loci at Chromosomes 15q25, 5p15, and 6p21: A Pooled Analysis From the International Lung Cancer Consortium. Journal of the National Cancer Institute 102: 959-‐71. Timofeeva M., Kropp S., Sauter W., Beckmann L., Rosenberger A., Illig T., Jäger B., Mittelstrass K., Dienemann H., Bartsch H., Bickeböller H., Chang-‐Claude J., Risch A., Wichmann H.E.; The LUCY Consortium. (2010) Genetic polymorphisms of MPO, GSTT1, GSTM1, GSTP1, EPHX1 and NQO1 as risk factors of early-‐onset lung cancer. International Journal of Cancer 127: 1547-‐1561. Scherf D.B., Dally H., Müller P., Werle-‐Schneider G., Jäger B., Edler L., Tuengerthal S., Fischer J.R., Drings P., Bartsch H., Risch A. (2010) SNPs in Matrix metalloproteinase genes and lung cancer chemotherapy response and prognosis. European Respiratory Journal 35: 381-‐90. Field J.K., Liloglou T., Niaz A., Bryan J., Gosney J., Giles T., Brambilla C., Brambilla E., Vesin A., Timsit J.-‐F., Hainaut P., Martinet Y., Vignaud J.M., Thunnissen F.B., Prinsen C., Snijders P.J., Smit E.F., Sozzi G., Roz L., Risch A., Becker H.D., Elborn J.S., Magee N., Montuenga L.M., Pajares M.J., Lozano M.D., O'Byrne K.J., Harrison D.J., Niklinski J., Cassidy A. and the EUELC consortium (2009) European Early Lung Cancer (EUELC) Project: A multi-‐centre, multipurpose study to investigate early stage non-‐small cell lung cancer (NSCLC), and to establish a biobank for ongoing collaboration. European Respiratory Journal 34: 1477-‐86. Landi M.T., Chatterjee N., Yu K., Goldin L.R., Goldstein A.M., Rotunno M., Mirabello L., Jacobs K., Wheeler W., Yeager M., Bergen A.W., Li Q., Consonni D., Pesatori A.C., Wacholder S., Thun M., Diver R.,
Oken M., Virtamo J., Albanes D., Wang Z., Burdette L., Doheny K.F., Pugh E.W., Laurie C., Brennan P., Hung R., Gaborieau V., McKay J.D., Lathrop M., McLaughlin J., Wang Y., Tsao M.S., Spitz M.R., Wang Y., Krokan H., Vatten L., Skorpen F., Arnesen E., Benhamou S., Bouchard C., Metsapalu A., Vooder T., Nelis M., Välk K., Field J.K., Chen C., Goodman G., Sulem P., Thorleifsson G., Rafnar T., Eisen T., Sauter W., Rosenberger A., Bickeböller H., Risch A., Chang-‐Claude J., Wichmann H.E., Stefansson K., Houlston R., Amos C.I., Fraumeni J.F. Jr, Savage S.A., Bertazzi P.A,. Tucker M.A., Chanock S., Caporaso N.E. (2009) A genome-‐wide association study of lung cancer identifies a region of chromosome 5p15 associated with risk for adenocarcinoma. American Journal of Human Genetics 85: 679-‐91. Timofeeva M., Kropp S., Sauter W., Beckmann L., Rosenberger A.., Illig T., Jaeger B., Mittelstrass K., Dienemann H., Bartsch H., Bickeböller H., Chang-‐Claude J., Risch A., Wichmann H.E. (2009) CYP 450 polymorphisms as risk factors for early onset lung cancer: gender specific differences. Carcinogenesis 30: 1161-‐9. Timofeeva M., Jäger B., Rosenberger A., Sauter W., Wichmann H.-‐E., KORA Study Group, Bickeböller H., Risch A. (2009) A multiplex real-‐time PCR method for detection of GSTM1 and GSTT1 copy numbers. Clinical Biochemistry 42: 500-‐509. Müller P.J., Dally H., Klappenecker C., Edler L., Jäger B., Gerst M., Spiegelhalder B., Tuengerthal S., Fischer J.R., Drings P., Bartsch H., Risch A. (2008) Polymorphisms in ABCG2, ABCC3 and CNT1 genes and their possible impact on chemotherapy outcome of lung cancer patients. International Journal of Cancer 124: 1669-‐74. Sauter W., Rosenberger A., Beckmann. L., Kropp S., Mittelstrass K., Timofeeva M., Wölke G., Steinwachs A., Scheiner D., Meese E., Sybrecht G., Kronenberg F., Dienemann H., Chang-‐Claude J., Illig T., the LUCY-‐Consortium, Wichmann H.-‐E., Bickeböller H., Risch A. (2008) Matrix Metalloproteinase-‐1 (MMP1) associated with early onset lung cancer. Cancer Epidemiology Biomarkers and Prevention 17: 1127-‐35. Mittelstrass K, Sauter W , Rosenberger A., Illig T., Timofeeva M., Klopp N., Dienemann H., Meese E., Sybrecht G., Woelke G., Cebulla M., Degen M., Morr H., Drings P., Groeschel A., Grosse Kreymborg K., Haeußinger K., Hoeffken G., Schmidt C., Jilge B., Schmidt W., Ko Y-‐D., Taeuscher D., Chang-‐Claude J., Wichmann H-‐E., Bickeboeller H., Risch A. (2008) Early onset lung cancer, cigarette smoking and the SNP309 of the murine double minute-‐2 (MDM2) gene, BMC Cancer 8: 113. Cox A., Dunning A.M., Garcia-‐Closas M., Balasubramanian S., Reed M.W.R., Pooley K. A., Scollen S., Baynes C., Ponder B.A. J., Chanock S., Lissowska J., Brinton L., Peplonska B., Southey M.C., Hopper J.L., McCredie M.R.E., Giles G.G., Fletcher O., Johnson N., dos Santos Silva I., Gibson L., Bojesen S.E., Nordestgaard B.G., Axelsson C.K., Torres D., Hamann U., Justenhoven C., Brauch H., Chang-‐Claude J., Kropp S., Risch A., Wang-‐Gohrke S., Schürmann P., Bogdanova N., Dörk T., Fagerholm R., Aaltonen K., Blomqvist C., Nevanlinna H., Seal S., Renwick A., Stratton M.R., Rahman N., Sangrajrang S., Hughes D., Odefrey F., Brennan P., Spurdle A.B., Chenevix-‐Trench G., Beesley J., The Katherine Cuningham Foundation Consortium for Research into Familial Breast Cancer, Mannermaa A., Hartikainen J., Kataja V., Kosma V.-‐M.,. Couch F.J, Olson J.E., Goode E.L., Broeks A., Schmidt M.K., Hogervorst F.B.L.,. Van’t Veer L.J, Kang D., Yoo K.-‐Y., Noh D.-‐Y., Ahn S.-‐H., Wedren S., Hall P., Low Y.-‐L., Liu J., Milne R.L., Ribas G., Gonzalez-‐Neira A., Benitez J., Sigurdson A.J., Stredrick D.L., Alexander B.H., Struewing J.P., Pharoah P.D.P., Easton D.F., on behalf of the Breast Cancer Association Consortium (2007) A common coding variant in CASP8 is associated with breast cancer risk. Nature Genetics 39:352-‐358. + corrigendum Nature Genetics 39: 688. Dally H., Bartsch H., Jäger B., Edler L., Schmezer P., Spiegelhalder B., Dienemann H., Drings P., Kayser K., Schulz V., Risch A. (2004) Genotype relationships in the CYP3A locus in Caucasians. Cancer Letters 207: 95-‐99.
Dally H., Edler L., Jäger B., Schmezer P., Spiegelhalder B., Dienemann H., Drings P., Schulz V., Kayser K., Bartsch H., Risch A. (2003) The CYP3A4*1B allele increases risk for small cell lung cancer: effect of gender and smoking dose. Pharmacogenetics 13: 607-‐618. Risch A., Ramroth H., Raedts V., Rajaee-‐Behbahani N., Schmezer P., Bartsch H., Becher H., Dietz A.(2003) Genetic Polymorphisms in class I alcohol dehydrogenases ADH1B and ADH1C, and glutathione-‐S-‐transferases GSTM1 and GSTT1 do not significantly modify the alcohol-‐ and tobacco smoke-‐associated laryngeal cancer risk. Pharmacogenetics 13: 225-‐230. Dally H., Gassner K., Jäger B., Schmezer P., Spiegelhalder B., Edler L., Drings P., Dienemann H., Schulz V., Kayser K., Bartsch H., Risch A. (2002) The Myeloperoxidase –463 G>A variant allele is associated with reduced risk for Small Cell Lung Cancer in smokers. International Journal of Cancer 102: 530-‐535. Risch A., Wikman H., Thiel S., Schmezer P., Edler L., Drings P., Dienemann H., Kayser K., Schulz V., Spiegelhalder B., Bartsch H. (2001) Glutathione-‐S-‐Transferase M1, M3, T1, P1 Polymorphisms and Susceptibility to Non-‐Small Cell Lung Cancer Subtypes and Hamartomas. Pharmacogenetics 11: 757-‐764. Wikman H., Thiel S., Jäger B., Schmezer P., Spiegelhalder B., Edler L., Dienemann H., Kayser K., Schulz V., Drings P., Bartsch H., Risch A. (2001) Relevance of N-‐Acetyltransferases 1 and 2 (NAT1, NAT2) Genetic Polymorphisms in non-‐Small Cell Lung Cancer. Pharmacogenetics 11: 157-‐168. Risch A., Smelt, V., Lane, D., Stanley, L., van der Slot, W., Ward, A., Sim, E. (1996) Arylamine N-‐Acetyltransferase in Erythrocytes of Cystic fibrosis Patients. Pharmacology and Toxicology 78: 235-‐240. Risch A., Wallace D.M.A., Bathers S., Sim E. (1995) Slow N-‐acetyltransferase genotype is a susceptibility factor in occupational and smoking induced bladder cancer. Human Molecular Genetics 4: 231-‐236.