Experimental Cancer Genetics

Roland Rad

Roland Rad graduated from TUM in 2001 with a degree in medicine and did his doctoral studies and clinical training at the Department of Medicine II, Klinikum Rechts der Isar (TUM). Between 2006 and 2013 he worked with Professor Allan Bradley as a postdoctoral fellow and senior clinical scientist at the Wellcome Trust Sanger Institute, Cambridge, UK. In 2012 he was appointed professor for translational GI Oncology at TUM and the German Consortium for Translational Cancer Research (DKTK) at the German Cancer Research Center (DKFZ, Heidelberg). Since 2018 he is also director of the Institute of Molecular Oncology and Functional Genomics at TUM (www.imo.med.tum.de).

Research Focus

Genome sequencing has provided tremendous insights into the mutational landscapes in cancer, but has also revealed that we are far from understanding the complexity of the molecular processes

To address these challenges, the Rad group has developed transposon-based screening technologies in mice. These tools allow the discovery of cancer-driving molecular processes, which are difficult to identify with other methods. The team is utilizing these systems to uncover mechanisms of tumour evolution, metastatic spread and treatment resistance directly in vivo, in a high-throughput manner, on a genome-wide scale. Their ongoing screens (and those of scientists worldwide using the group’s mouse models) are currently creating comprehensive catalogues of cancer-causing genes for various solid and haematological cancers, thus complementing the sequencing-based census of human cancer genes.

Another focus of the team is the development of high-throughput approaches for the analysis of gene function. This includes high-throughput conventional gene targeting strategies (currently creating a mouse embryonic stem cell resource for several hundred human oncogenes) and the development of CRISPR/Cas9-based approaches for somatic genome engineering in various organs of adult mice. The group has recently reported the first direct in vivo screens using CRISPR/Cas9 and the first examples of targeted somatic engineering of interchromosomal translocations in mice. Such somatic genome editing approaches are beginning to dramatically facilitate the functional annotation of cancer genomes, a major challenge in cancer research for the coming decades.

In independent reverse genetic approaches, the group is using conventional gene targeting to develop mouse models of digestive tract cancers and their sub-entities. These models are being used to study molecular signalling as well as for pre-clinical drug testing to uncover novel targets for cancer therapy.

The group also provides core sequencing and bioinformatics support at the RDI campus, including next generation sequencing applications for the analysis of mouse and human cancer genomes.

Key Awards

  • Dr. Emil Salzer Prize, from the German Cancer Research Center, DKFZ (2014)
  • Rising Star Award from the United European Gastroenterology Association, UEG (2014)
  • Research Fellowship from the German Research Foundation, DFG (2006)
  • Dietmar-Zumpf Award from the Dietmar Zumpf Foundation (20004)
  • Fellowship from "Bund der Freunde der Technischen Universität München" (2004)

Selected Publications

  • Mueller S, Engleitner T, Maresch R, Zukowska M, Lange S, Kaltenbacher T, Konukiewitz B, Öllinger R, Zwiebel M, Strong A, Yen HY, Banerjee R, Louzada S, Fu B, Seidler B, Götzfried J, Schuck K, Hassan Z, Arbeiter A, Schönhuber N, Klein S, Veltkamp C, Friedrich M, Rad L, Barenboim M, Ziegenhain C, Hess J, Dovey OM, Eser S, Parekh S, Constantino-Casas F, de la Rosa J, Sierra MI, Fraga M, Mayerle J, Klöppel G, Cadiñanos J, Liu P, Vassiliou G, Weichert W, Steiger K, Enard W, Schmid RM, Yang F, Unger K, Schneider G, Varela I, Bradley A, Saur D, Rad R, Evolutionary routes and KRAS dosage define pancreatic cancer phenotypes, Nature 1;554(7690):62-68 (2018).
  • Weber J, Öllinger R, Friedrich M, Ehmer U, Barenboim M, Steiger K, Heid I, Mueller S, Maresch R, Engleitner T, Gross N, Geumann U, Fu B, Segler A, Yuan D, Lange S, Strong A, de la Rosa J, Esposito I, Liu P, Cadiñanos J, Vassiliou GS, Schmid RM, Schneider G, Unger K, Yang F, Braren R, Heikenwälder M, Varela I, Saur D, Bradley A, Rad R, CRISPR/Cas9 somatic multiplex-mutagenesis for high-throughput functional cancer genomics in mice, PNAS 112(45):13982–7 (2015).
  • Rad R, Rad L, Wang W, Strong A, Ponstingl H, Bronner I, Mayho M, Steiger K, Weber J, Hieber M, Veltkamp C, Eser S, Geumann U, Öllinger R, Zukowska M, Barenboim M, Cadiñanos J, Friedrich M, Varela I, Constantino-Casas F, Sarver A, ten Hoeve J, Prosser H, Seidler B, Bauer J, Heikenwälder M, Metzakopian E, Krug A, Ehmer U, Schneider G, Knösel T, Rümmele P, Aust D, Grützmann R, Pilarsky C, Ning Z, Wessels L, Schmid RM, Quail MA, Vassilliou GS, Esposito I, Liu P, Saur D, Bradley A, A conditional PiggyBac transposition system for genetic screening in mice identifi es oncogenic networks in pancreatic cancer, Nature Genetics 47(1):47–56 (2015).
  • Rad R, Cadiñanos J, Rad L, Varela I, Strong A, Kriegl L, Constantino-Casas F, Eser S, Hieber M, Seidler B, Price S, Fraga MF, Calvanese V, Hoffman G, Ponstingl H, Schneider G, Yusa K, Grove C, Schmid RM, Wang W, Vassiliou G, Kirchner T, McDermott U, Liu P, Saur D, Bradley A, A genetic progression model of BrafV600E-induced intestinal tumorigenesis reveals targets for therapeutic intervention, Cancer Cell 24(1):15–29 (2013).
  • Rad R, Rad L, Wang W, Cadiñanos J, Vassiliou G, Rice S, Campos LS, Yusa K, Banerjee R, Li MA, Strong A, Lu D, Ellis P, Conte N, Yang FT, Liu P, Bradley A, PiggyBac transposon mutagenesis: a tool for cancer gene discovery in mice, Science 330(6007):1104–7 (2010)