Friedel Lab

Molecular Mechanisms of Brain Tumorigenesis

Research

Roland FriedelBrain tumors remain a deadly form of cancer. Our research goal is to provide a better understanding of the molecular machinery that drives proliferation, invasiveness, and therapy resistance of brain tumor cells. We aim to provide insights that will allow development of new targeted therapies against brain tumor cells.

Our research team focuses on the question of how axon guidance molecules regulate migration and proliferation of brain tumor cells. We are also investigating the molecular characteristics that define brain tumor stem cells by using molecular reporters.

Projects

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.

Axon guidance molecules control cellular dynamics and malignancy of glioma cells

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. A particular effort is on elucidating the role of Plexin-B2, an axon guidance receptor that plays an important role in formation of the developing nervous system, and which is highly expressed in malignant glioblastoma.

Cellular and molecular characteristics of glioblastoma stem cells

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.

Contact Us

Friedel Laboratory
Roland Friedel, PhD
Assistant Professor, Neuroscience
Assistant Professor, Neurosurgery
Location
Office: ICAHN 10-20F
Phone
Office: 212.659.5529
Email

Featured

Impaired cortical neurogenesis in plexin-B1 and -B2 double deletion mutant

Mammalian cortical expansion is tightly controlled by fine-tuning of proliferation and differentiation of neural progenitors in a region-specific manner. How extrinsic cues interface with cell-intrinsic programs to balance proliferative versus neurogenic decisions remains an unsolved question.

Daviaud, N., Chen, K., Huang, Y., Friedel, R.H., and Zou, H. (2016). Dev Neurobiol 76, 882-899.

Publications

2016

Loh, Y.E., Koemeter-Cox, A., Finelli, M., Shen, L., Friedel, R.H., and Zou, H. (2016). Comprehensive mapping of 5-hydroxymethylcytosine epigenetic dynamics in axon regeneration. Epigenetics, 0.


Xue, D., Kaufman, G.N., Dembele, M., Beland, M., Massoud, A.H., Mindt, B.C., Fiter, R., Fixman, E.D., Martin, J.G., Friedel, R.H., et al. (2016). Semaphorin 4C Protects against Allergic Inflammation: Requirement of Regulatory CD138+ Plasma Cells. J Immunol.


Daviaud, N., Chen, K., Huang, Y., Friedel, R.H., and Zou, H. (2016). Impaired cortical neurogenesis in plexin-B1 and -B2 double deletion mutant. Dev Neurobiol 76, 882-899.

2015

Wong, J.K., Chen, L., Huang, Y., Sehba, F.A., Friedel, R.H., and Zou, H. (2015). Attenuation of Cerebral Ischemic Injury in Smad1 Deficient Mice. PLoS One 10, e0136967.


Xia, J., Swiercz, J.M., Banon-Rodriguez, I., Matkovic, I., Federico, G., Sun, T., Franz, T., Brakebusch, C.H., Kumanogoh, A., Friedel, R.H., et al. (2015). Semaphorin-Plexin Signaling Controls Mitotic Spindle Orientation during Epithelial Morphogenesis and Repair. Dev Cell 33, 299-313.


Le, A.P., Huang, Y., Pingle, S.C., Kesari, S., Wang, H., Yong, R.L., Zou, H., and Friedel, R.H. (2015). Plexin-B2 promotes invasive growth of malignant glioma. Oncotarget 6, 7293-7304.


Zou, H., Feng, R., Huang, Y., Tripodi, J., Najfeld, V., Tsankova, N.M., Jahanshahi, M., Olson, L.E., Soriano, P., and Friedel, R.H. (2015). Double minute amplification of mutant PDGF receptor alpha in a mouse glioma model. Sci Rep 5, 8468.

2014

Azzarelli, R., Pacary, E., Garg, R., Garcez, P., van den Berg, D., Riou, P., Ridley, A.J., Friedel, R.H., Parsons, M., and Guillemot, F. (2014). An antagonistic interaction between PlexinB2 and Rnd3 controls RhoA activity and cortical neuron migration. Nat Commun 5, 3405.

2013

Kuzirian, M.S., Moore, A.R., Staudenmaier, E.K., Friedel, R.H., and Paradis, S. (2013). The class 4 semaphorin Sema4D promotes the rapid assembly of GABAergic synapses in rodent hippocampus. J Neurosci 33, 8961-8973.


Friedel, R.H., Friedel, C.C., Bonfert, T., Shi, R., Rad, R., and Soriano, P. (2013). Clonal expansion analysis of transposon insertions by high-throughput sequencing identifies candidate cancer genes in a PiggyBac mutagenesis screen. PLoS One 8, e72338.

2012

Bradley, A., Anastassiadis, K., Ayadi, A., Battey, J.F., Bell, C., Birling, M.C., Bottomley, J., Brown, S.D., Burger, A., Bult, C.J., et al. (2012). The mammalian gene function resource: the International Knockout Mouse Consortium. Mamm Genome 23, 580-586.

Meet the Team

Rut Tejero-Villalba

Rut Tejero-Villalba

Postdoctoral Fellow

rut.tejero-villalba@mssm.edu

Rui Feng

Rui Feng

Medical Student

rui.feng@icahn.mssm.edu

Yong Huang

Yong Huang

Associate Scientist

yong.huang@mssm.edu

Alexandra Miner

Alexandra Miner

Master Student

alexandra.miner@icahn.mssm.edu