Cohen/Herranz Group – University of Copenhagen

Forward this page to a friend Resize Print Bookmark and Share

Department of Cellular and Molecular Medicine > Research Groups > Cohen/Herranz Group

Cohen/Herranz Group

Morphogenesis and Differentiation Program

Research Interest

Analysis of gene functions in development and disease, using Drosophila

Background

Cancer develops in a complex mutational landscape. Cancer cells accumulate ‘driver mutations’ that are causally linked to disease, and ‘passenger mutations’ that, although present, have limited impact on disease. In recent years, factors encoded by cancer genes have become targets for successful anticancer drug development. Although cancer genome sequence data provide an unparalleled depth of information about the mutations present in different cancer genomes, identification of genetic alterations contributing to tumorigenesis and metastasis calls for the use of simple genetic model systems.

We have engineered Drosophila strains that activate different cancer-driver mutations. These flies allow, with a single genetic cross, the introduction of new mutations to identify genes that, when combined with driver mutations, lead to tumor formation and metastasis.

The Figure above illustrates the oncogenic interaction between the oncogene EGFR and the gene psq.

 Specific aims

(1) understand how different mutations cooperate during the process of cellular transformation

(2) study the oncogenic potential of epithelial tetraploid cells that result from cytokinesis failure

(3) better understand how the metabolic changes taking place in cancer cells contribute to cellular transformation and metastasis

(4) determine the role that miRNAs play in growth control during normal development and cancer

Current project areas

  • Genetic models of oncogene cooperation
  • microRNAs in growth control, development, and cancer
  • Cytokinesis failure and cancer
  • Cancer metabolism
  • DISC-B: Denmark-India in vivo Screen for Cancer Biomarkers

Selected publications

  • Song S, Herranz H & Cohen SM.  The chromatin remodeling BAP complex limits tumor promoting activity of the Hippo pathway effector Yki to prevent neoplastic transformation in Drosophila epithelia. Dis Model Mech. 2017 Oct 1;10(10):1201-1209.

  • Aw, S.S., Lim, I.K.H., Tan, M.X.M. & Cohen S.M. (2017) A glio-protective role of mir-263a by tuning sensitivity to glutamate. Cell Reports, 2017 Oct 1;10(10):1201-1209.

  • Foo, L.C., Song, S., & Cohen, S.M. (2017) Evidence for ongoing glial homeostasis in the adult Drosophila brain revealed by miR-31 mutants. EMBO J Published online 20.03.2017

  • Eichenlaub T, Cohen SM & Herranz H. Cell competition drives the formation of metastatic tumors In a Drosophila model of epithelial tumor formation. Current Biology. 26, 1–9 February 22, 2016

  • Herranz H, Eichenlaub T & Cohen SM. Cancer in Drosophila: imaginal discs as a model for epithelial tumor formation. Curr Top Dev Biol. 116:181-99. Feb 2016.

  • Chen Y-W, Song, S., Weng, R., Verma, P., Kugler, J.-M., Buescher, M., Rouam, S., & Cohen, S.M. (2014). Systematic study of Drosophila microRNA functions using a collection of targeted knockout mutations. Dev Cell, in press

  • Herranz H, Weng R and Cohen SM*. Crosstalk between Epithelial and Mesenchymal Tissues in Tumorigenesis and Imaginal Disc. Current Biology. 24, 1–9, July 7, 2014.

  • Foronda, D., Weng, R., Verma, P., Chen. Y.-W. & Cohen S.M. (2014) Coordination of Insulin and Notch pathway activities by microRNA miR-305 mediates adaptive homeostasis in the intestinal stem cells of the Drosophila gut. Genes Dev 28: 2421-2431.

  • Hong, X., Nguyen H.T., Chen Q., Zhang, R., Hagman, Z., Voorhoeve, P.M. & Cohen, S.M. (2014). Opposing activities of the Ras and Hippo pathways converge on regulation of YAP protein turnover. EMBO J

  • Nguyen H.T., Hong, X., Tan, S., Chen Q., Chan,L., Fivaz.M., Cohen, S.M. & Voorhoeve, P.M. (2014) Viral small T oncoproteins transform cells by alleviating Hippo pathway-mediated inhibition of the YAP proto-oncogene. Cell Reports 8, 707-713.

  • Herranz H*, Weng R and Cohen SM*. Crosstalk between Epithelial and Mesenchymal Tissues in Tumorigenesis and Imaginal Disc. Current Biology, 24, 1–9, July 7, 2014 *Corresponding author Access the recommendation on F1000Prime

  • Zhang, W., Hietakangas,V., Wee, S.,  Lim, R.  Gunaratne, J., and Cohen, S.M.  (2013) ER stress potentiates insulin resistance through PERK-mediated FOXO phosphorylation. Genes Dev 27(4):441-9

  • Herranz H*, Hong X*, Hung NT, Voorhoeve PM and Cohen SM. Oncogenic cooperation between SOCS family proteins and EGFR identified using a Drosophila epithelial transformation model. Genes Dev, 2012 Jul 15; 26: 1602-1611 *These authors contributed equally to this work.

  • Herranz H, Hong X and Cohen SM. Mutual Repression by Bantam miRNA and Capicua Links the EGFR/MAPK and Hippo Pathways in Growth Control. Current Biology, 22, 1–7, April 24, 2012

  • Herranz H and Cohen SM. MicroRNAs and gene regulatory networks: managing the impact of noise in biological systems. Genes Dev, 2010 Jul 1;24(13):1339-44

  • Herranz H, Hong X, Pérez L, Ferreira A, Olivieri D, Cohen SM and Milán M. The miRNA machinery targets Mei-P26 and regulates Myc protein levels in the Drosophila wing. EMBO J, 2010 May 19;29(10)

  • Varghese, J., Lim, S., and SM Cohen (2010) Drosophila miR-14 regulates insulin production and metabolism through its target sugarbabe. Genes Dev. 24: 2748-2753.

  • Hong, X., Hammell, M. Ambros, V and Cohen, S.M. (2009) Identification of microRNA targets by immunopurification of Ago1 RNPs: selection for a distinct class of targets. Proc Natl Acad Sci USA 106, 15085-90.

  • Bushati, N., Stark, A., Brennecke, J., and Cohen, S.M. (2008) Temporal reciprocity of microRNAs and their targets during the maternal to zygotic transition in Drosophila. Current Biology 18, 501-506.

  • J Karres, V Hilgers, I Carrera, J Treisman & SM Cohen (2007) The conserved microRNA miR-8 tunes Atrophin levels to prevent neurodegeneration in Drosophila. Cell 131, 136–145.

  • BJ Thompson & SM Cohen (2006) The Hippo pathway regulates the bantam microRNA to control cell proliferation and apoptosis in Drosophila. Cell.126, 767-774.

  • Stark, A., Brennecke, J., Bushati, N. Russell, R.B. & Cohen, S.M. (2005) Animal microRNAs confer robustness to gene expression and have a significant impact on 3’UTR evolution. Cell 123,1133-1146.

  • Brennecke, J., Hipfner, D.R. Stark, A., Russell, R & Cohen, S.M. (2003) bantam encodes a developmentally regulated microRNA that controls cell proliferation and regulates the pro-apoptotic gene hid in Drosophila. Cell 113: 25-36.