Roland Friedel, PhD
- ASSISTANT PROFESSOR | Neuroscience
- ASSISTANT PROFESSOR | Neurosurgery
Research Topics:Axon Guidance, Developmental Neurobiology, Epigenetics, Genetics, Human Genetics and Genetic Disorders, Neuro-degeneration/protection, Regeneration, Stem Cells
Dr. Roland Friedel, is an expert in the fields of developmental neurobiology and brain tumor research. His research team focuses on the question of how axon guidance molecules and growth factors regulate the migration and differentiation of brain tumor cells. He is also investigating the molecular characteristics that define brain tumor stem cells.
Multi-Disciplinary Training AreasCancer Biology [CAB], Developmental and Stem Cell Biology [DSCB], Neuroscience [NEU]
Ph D, University of Munich
Postdoctoral, Stanford University
Tumors of the brain are amongst the most lethal types of cancer. They account for over 175,000 cases per year worldwide, claiming the lives of thousands of patients (WHO World Cancer Report). Despite significant progress in the identification of genes involved in tumorigenesis, the etiology of brain tumors is still largely unknown, and incidence and mortality rates of these cancers have changed little over the past decade. The goal of our research is to identify the genetic factors that contribute to the formation and spreading of brain tumors. The identification of novel diagnostic markers and therapeutic targets will lead to better treatment strategies for this devastating disease.
To identify novel molecules that regulate the invasive spreading behavior of brain tumor cells, we are performing functional genetic analyses with human glioma stem cell lines in vitro and in transplantation assays in vivo. We are focusing our studies on candidate genes of the axon guidance families and their downstream signaling components.
To study the role of PDGF growth factor signaling in glioma, we are investigating a genetic mouse model of glioma that is driven by over-activity of the PDGF receptor alpha. Tumors are studied by cytogenetic and genomic analysis of tumor tissue and glioma stem cell lines.
Brain tumor stem cells are believed to be a special subpopulation that exhibits enhanced tumorigenic capacity and resistance to conventional therapy. To identify underlying molecular mechanisms that control brain tumor stem cells in their migratory, self-renewal, and proliferative behaviors, we have engineered glioma cells with a cell division marker H2B-GFP. Cellular and molecular characteristics of cells with different cell division history are studied in orthotopic transplant models.
Le AP, Huang Y, Pingle SC, Kesari S, Wang H, Yong RL, Zou H, Friedel RH. Plexin-B2 promotes invasive growth of malignant glioma. Oncotarget 2015 Mar; 6(9).
Zou H, Feng R, Huang Y, Tripodi J, Najfeld V, Tsankova NM, Jahanshahi M, Olson LE, Soriano P, Friedel RH. Double minute amplification of mutant PDGF receptor α in a mouse glioma model. Scientific Reports 2015; 5.
Xia J, Swiercz JM, Bañón-Rodríguez I, Matković I, Federico G, Sun T, Franz T, Brakebusch CH, Kumanogoh A, Friedel RH, Martín-Belmonte F, Gröne HJ, Offermanns S, Worzfeld T. Semaphorin-Plexin Signaling Controls Mitotic Spindle Orientation during Epithelial Morphogenesis and Repair. Developmental Cell 2015 May; 33(3).
Azzarelli R, Pacary E, Garg R, Garcez P, van den Berg D, Riou P, Ridley AJ, Friedel RH, Parsons M, Guillemot F. An antagonistic interaction between PlexinB2 and Rnd3 controls RhoA activity and cortical neuron migration. Nature Communications 2014; 5.
Friedel RH, Friedel CC, Bonfert T, Shi R, Rad R, Soriano P. Clonal Expansion Analysis of Transposon Insertions by High-Throughput Sequencing Identifies Candidate Cancer Genes in a PiggyBac Mutagenesis Screen. PLOS ONE 2013; 8(8).
Kuzirian MS, Moore AR, Staudenmaier EK, Friedel RH, Paradis S. The class 4 semaphorin Sema4D promotes the rapid assembly of GABAergic synapses in rodent hippocampus. Journal of Neuroscience 2013 May; 33(21).
Bradley A, Anastassiadis K, Ayadi A, Battey JF, Bell C, Birling MC, Bottomley J, Brown SD, Bürger A, Bult CJ, Bushell W, Collins FS, Desaintes C, Doe B, Economides A, Eppig JT, Finnell RH, Fletcher C, Fray M, Frendewey D, Friedel RH, Grosveld FG, Hansen J, Hérault Y, Hicks G, Hörlein A, Houghton R, Hrabé de Angelis M, Huylebroeck D, Iyer V, de Jong PJ, Kadin JA, Kaloff C, Kennedy K, Koutsourakis M, Lloyd KC, Marschall S, Mason J, McKerlie C, McLeod MP, von Melchner H, Moore M, Mujica AO, Nagy A, Nefedov M, Nutter LM, Pavlovic G, Peterson JL, Pollock J, Ramirez-Solis R, Rancourt DE, Raspa M, Remacle JE, Ringwald M, Rosen B, Rosenthal N, Rossant J, Ruiz Noppinger P, Ryder E, Schick JZ, Schnütgen F, Schofield P, Seisenberger C, Selloum M, Simpson EM, Skarnes WC, Smedley D, Stanford WL, Stewart AF, Stone K, Swan K, Tadepally H, Teboul L, Tocchini-Valentini GP, Valenzuela D, West AP, Yamamura K, Yoshinaga Y, Wurst W. The mammalian gene function resource: the International Knockout Mouse Consortium. Mammalian Genome 2012 Oct; 23(9-10).
Maier V, Jolicoeur C, Rayburn H, Takegahara N, Kumanogoh A, Kikutani H, Tessier-Lavigne M, Wurst W, Friedel RH. Semaphorin 4C and 4G are ligands of Plexin-B2 required in cerebellar development. Molecular and Cellular Neuroscience 2011;.
Negishi-Koga T, Shinohara M, Komatsu N, Bito H, Kodama T, Friedel RH, Takayanagi H. Suppression of bone formation by osteoclastic expression of semaphorin 4D. Nature Medicine 2011;.
Friedel RH, Wurst W, Wefers B, Kühn R. Generating conditional knockout mice. Methods in Molecular Biology 2011;.
Leslie JR, Imai F, Fukuhara K, Takegahara N, Rizvi TA, Friedel RH, Wang F, Kumanogoh A, Yoshida Y. Ectopic myelinating oligodendrocytes in the dorsal spinal cord as a consequence of altered semaphorin 6D signaling inhibit synapse formation. Development 2011;.
Friedel RH, Soriano P. Gene trap mutagenesis in the mouse. Methods in Enzymology 2010;.
Takamatsu H, Takegahara N, Nakagawa Y, Tomura M, Taniguchi M, Friedel RH, Rayburn H, Tessier-Lavigne M, Yoshida Y, Okuno T, Mizui M, Kang S, Nojima S, Tsujimura T, Nakatsuji Y, Katayama I, Toyofuku T, Kikutani H, Kumanogoh A. Semaphorins guide the entry of dendritic cells into the lymphatics by activating myosin II. Nature Immunology 2010;.
Okuno T, Nakatsuji Y, Moriya M, Takamatsu H, Nojima S, Takegahara N, Toyofuku T, Nakagawa Y, Kang S, Friedel RH, Sakoda S, Kikutani H, Kumanogoh A. Roles of Sema4D-plexin-B1 interactions in the central nervous system for pathogenesis of experimental autoimmune encephalomyelitis. Journal of Immunology 2010;.
Zielonka M, Xia J, Friedel RH, Offermanns S, Worzfeld T. A systematic expression analysis implicates Plexin-B2 and its ligand Sema4C in the regulation of the vascular and endocrine system. Experimental Cell Research 2010;.
Friedel RH. Targeting embryonic stem cells. Methods in Molecular Biology 2009;.
Korostylev A, Worzfeld T, Deng S, Friedel RH, Swiercz JM, Vodrazka P, Maier V, Hirschberg A, Ohoka Y, Inagaki S, Offermanns S, Kuner R. A functional role for Semaphorin 4D/Plexin B1 interactions in epithelial branching morphogenesis during organogenesis. Development 2008;.
Friedel RH, Kerjan G, Rayburn H, Schuller U, Sotelo C, Tessier-Lavigne M, Chedotal A. Plexin-B2 controls the development of cerebellar granule cells. Journal of Neuroscience 2007;.
Friedel RH, Seisenberger C, Kaloff C, Wurst W. EUCOMM--the European conditional mouse mutagenesis program. Briefings in Functional Genomics and Proteomics 2007;.
Friedel RH, Plump A, Lu X, Spilker K, Jolicoeur C, Wong K, Venkatesh TR, Yaron A, Hynes M, Chen B, Okada A, McConnell SK, Rayburn H, Tessier-Lavigne M. Gene targeting using a promoterless gene trap vector is an efficient method to mutate a large fraction of genes. Proceedings ot the National Academy of Sciences of the U S A 2005;.