Dr. med. Cornelius Miething

Our group is using functional genomic approaches to study the role of genetic and epigenetic signaling pathways in tumor development and maintenance, with a focus on malignant hematologic diseases like leukemia and lymphoma. By applying RNAi and CRISPR/CAS9-based techniques towards genetically defined tumor models, we aim to functionally dissect aberrant signaling networks in malignant disease, and translate the genetic information into more effective cancer treatments. We also use functional genetic tools to characterize essential response pathways towards targeted treatments, hoping to improve current therapeutic modalities by identifying novel synthetic lethal interactions as well as new biomarkers of response. Ongoing studies include a project on downstream targets of the Notch pathway in T-cell lymphoma/leukemia, a project on the role of PI3K signaling in Mantle-cell lymphoma, and a project dissecting epigenetic response modifiers in AML.

10 selected publications

• PTEN action in leukemia dictated by the tissue microenvironment.
  Miething C, Scuoppo C, Bosbach B, Appelmann I, Nakitandwe J, Ma J, Wu G, Lintault L, Auer M, Premsrirut PK, Teruya-Feldstein J, Hicks J, Benveniste H, Speicher MR, Downing JR, Lowe SW (2014)
  Nature 510, 402-406.
• Identification of a recurrent germline PAX5 mutation and susceptibility to pre-B cell acute lymphoblastic leukemia.
  Shah S, Schrader KA, Waanders E, Timms AE, Vijai J, Miething C, Wechsler J, Yang J, Hayes J, Klein RJ, Zhang J, Wei L, Wu G, Rusch M, Nagahawatte P, Ma J, Chen SC, Song G, Cheng J, Meyers P, Bhojwani D, Jhanwar S, Maslak P, Fleisher M, Littman J, Offit L, Rau-Murthy R, Fleischut MH, Corines M, Murali R, Gao X, Manschreck C, Kitzing T, Murty VV, Raimondi SC, Kuiper RP, Simons A, Schiffman JD, Onel K, Plon SE, Wheeler DA, Ritter D, Ziegler DS, Tucker K, Sutton R, Chenevix-Trench G, Li J, Huntsman DG, Hansford S, Senz J, Walsh T, Lee M, Hahn CN, Roberts KG, King MC, Lo SM, Levine RL, Viale A, Socci ND, Nathanson KL, Scott HS, Daly M, Lipkin SM, Lowe SW, Downing JR, Altshuler D, Sandlund JT, Horwitz MS, Mullighan CG, and Offit K (2013)
  Nat Genet 45, 1226-31.
  * equal contribution
• A tumour suppressor network relying on the polyamine-hypusine axis.
  Scuoppo C*, Miething C*, Lindqvist L, Reyes J, Ruse C, Appelmann I, Yoon S, Krasnitz A, Teruya-Feldstein J, Pappin D, Pelletier J, Lowe SW (2012)
  Nature 487, 244-248.
  * equal contribution
• A rapid and scalable system for studying gene function in mice using conditional RNA interference.
  Premsrirut PK, Dow LE, Kim SY, Camiolo M, Malone CD, Miething C, Scuoppo C, Zuber J, Dickins RA, Kogan SC, et al (2011)
  Cell 145, 145-158.
• Functional identification of tumor-suppressor genes through an in vivo RNA interference screen in a mouse lymphoma model.
  Bric A*, Miething C*, Bialucha CU*, Scuoppo C, Zender L, Krasnitz A, Xuan Z, Zuber J, Wigler M, Hicks J, McCombie RW, Hemann MT, Hannon GJ, Powers S, Lowe SW (2009)
  Cancer Cell 16, 324-335.
  * equal contribution
• Senescence and tumour clearance is triggered by p53 restoration in murine liver carcinomas.
  Xue W, Zender L, Miething C, Dickins RA, Hernando E, Krizhanovsky V, Cordon-Cardo C, Lowe SW (2007)
  Nature 445, 656-660.
• Retroviral insertional mutagenesis identifies RUNX genes involved in chronic myeloid leukemia disease persistence under imatinib treatment.
  Miething C, Grundler R, Mugler C, Brero S, Hoepfl J, Geigl J, Speicher MR, Ottmann O, Peschel C, Duyster J (2007)
  Proc Natl Acad Sci U S A 104, 4594-4599.
• The Bcr-Abl mutations T315I and Y253H do not confer a growth advantage in the absence of imatinib.
  Miething C, Feihl S, Mugler C, Grundler R, von Bubnoff N, Lordick F, Peschel C, Duyster J (2006)
  Leukemia 20, 650-657.
• Phosphorylation of tyrosine 393 in the kinase domain of Bcr-Abl influences the sensitivity towards imatinib in vivo.
  Miething C, Mugler C, Grundler R, Hoepfl J, Bai RY, Peschel C, Duyster J (2003)
  Leukemia 17, 1695-1699.
• The oncogenic fusion protein nucleophosmin-anaplastic lymphoma kinase (NPM-ALK) induces two distinct malignant phenotypes in a murine retroviral transplantation model
  Miething C, Grundler R, Fend F, Hoepfl J, Mugler C, von Schilling C, Morris SW, Peschel C, Duyster J (2003)
  Oncogene. 22, 4642-4647.