Institute of Biological and Chemical Systems - Functional Molecular Systems

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Friday, 25 October 2019
09:00 - 10:00 
IBCS-FMS internal seminar
Lecture
Bau 316 / Raum 105
Steffen Sonnentag, Orian-Rousseau


Friday, 24 January 2020
09:00 - 10:00 
Targeting tumor evolution to prevent drug resistance: a new strategy to prolong lung cancer response to EGFR inhibition
Lecture
Campus North, Building 316, Seminar room 105
Luca Grumolato, University of Rouen Normandie, France

Karlsruhe Institute of Technology, January 24th, 2020
Targeting tumor evolution to prevent drug resistance: a new strategy to prolong lung cancer response to EGFR inhibition
L. Grumolato, University of Rouen Normandie, France
 
Lung cancer is the leading cause of neoplastic-related mortality worldwide. The most common form of this disease, non-small cell lung cancer (NSCLC), is driven, in about 15% of the cases, by an activating mutation of the epidermal growth factor receptor (EGFR). NSCLC patients whose tumors display a mutant EGFR are treated with specific inhibitors of this receptor (EGFRi), such as gefitinib and osimertinib. However, after an initial response, the tumors invariably become resistant to these drugs, as a result of the emergence of subpopulations of resistant cells, which can be already present before the onset of the treatment. We recently devised CRISPR-barcoding, a novel approach to recapitulate and trace the emergence of a new mutation in a subset of cancer cells, thus enabling functional studies of a gene of interest in a context that mimics intratumor heterogeneity. We took advantage of this strategy to identify new compounds capable of preventing amplification of resistant clones from a mass population of NSCLC cells treated with EGFRi. Through a small molecule screen, we identified the multikinase inhibitor sorafenib for its capacity to prevent amplification of resistant cells in combination with EGFRi. We showed that sorafenib can prevent the emergence of clones displaying different mechanisms of resistance to EGFRi, including secondary EGFR mutations, overexpression of other receptor tyrosine kinases, such as MET and HER2, or aberrant activation of downstream effectors of the EGFR signaling, including KRAS, PIK3CA and BRAF. These results were confirmed in vivo, using a CRISPR-barcoding xenograft model of NSCLC resistance to EGFRi. Our data indicate that, in combination with an EGFRi, sorafenib preferentially targets resistant cells, resulting in an overall inhibition of therapy-induced tumor evolution. Mechanistically, we showed that the effects of sorafenib in NSCLC cells are independent of the MAPK pathway, and rely instead on the early inhibition of eIF4E and STAT3 phosphorylation, and the later downregulation of MCL1 and EGFR. Together, our results indicate that, by interfering with the positive selection of resistant clones, a co-treatment with sorafenib could substantially prolong NSCLC response to EGFR inhibition.
 
CRISPR-Barcoding for Intratumor Genetic Heterogeneity Modeling and Functional Analysis of Oncogenic Driver Mutations. Guernet A, Mungamuri SK, Cartier D, Sachidanandam R, Jayaprakash A, Adriouch S, Vezain M, Charbonnier F, Rohkin G, Coutant S, Yao S, Ainani H, Alexandre D, Tournier I, Boyer O, Aaronson SA, Anouar Y, Grumolato L. Mol Cell. 2016 Aug 4;63(3):526-38. doi: 10.1016/j.molcel.2016.06.017. Epub 2016 Jul 21.

Tuesday, 28 January 2020
09:00 - 10:00 
Publishing Talk by Advanced Materials Editors
Lecture
Campus North, Building 316, Seminar room 105
Jos Lenders and Dimitra Gkogkou, Advanced Materials editors (Wiley)

Publishing advanced materials science with Wiley under the Projekt DEAL “Publish & Read” agreement – How to maximize your success!
 
Materials science is a multidisciplinary field of research withmany differentscientists and engineers having various backgrounds active in it. The literature landscape consequently is populated currently by a wide range of journals which greatly differ in purpose, scope, quality, and readership. Jos Lenders (Deputy Editor of Adv Mater, Adv Funct Mater, and Adv Optical Mater) and Dimitra Gkogkou (Editor for Adv Funct Mater, Adv Optical Mater, and physica status solidi) will track some of the most important developments and trends in the research field and the Advanced journals program. Advanced Materials reached an Impact Factor of 25.809 and received over 8,400 submissions last year – and Advanced Functional Materials over 10,700. Only around 15% of all those papers made it to publication in these journals, and this rate is similar for all other Advanced journals. So, what do editors do to select the very best papers, and what can authors do to optimize their chances of having their manuscripts accepted? Jos and Dimitra hope to provide some insights into these topics. Key aspects are: structuring one’s research work well and assembling a convincing manuscript, understanding the decision processes in editorial offices, choosing an appropriate journal and knowing what to put in the cover letter, and which things to avoid. The talk will also cover the reasoning behind editorial workflows and the peer-review process, publishing ethics and best practices for authors and reviewers, and possibilities for open access. In addition, the talk will include an update on Projekt DEAL, the “Publish & Read” agreement between Wiley and a consortium of over 700 German universities and research institutes, allowing scientists from those organizations to have access to and publish Open Access in all of Wiley’s journals. Anybody who is enthused about where the field of materials science and its top-level publications will go next is more than welcome to join the seminar and discussion.
Biography Jos:
Dr. Jos Lenders is Deputy Editor of Advanced Materials, Advanced Functional Materials, and Advanced Optical Materials, and also edits Advanced Therapeutics. He studied chemical engineering with a minor in biomedical engineering and a master in polymers and composites at Eindhoven University of Technology, in the Netherlands. There he obtained his BSc, MSc, and PhD, the latter in the area of bioinspired materials synthesis and electron microscopy. He joined Wiley in 2015.
Biography Dimitra:
Dr. Dimitra Gkogkou studied physics at the University of Thessaloniki and earned a MSc in materials science. In 2013, she moved to Berlin to pursue research opportunities in the fields of plasmonics and spectroscopy, earning her PhD at the Technical University of Berlin and then carrying out post-doctoral research at the Leibniz-Institut für Analytische Wissenschaften - ISAS - e.V. She joined Wiley in 2019 as an Editor for Advanced Functional Materials, Advanced Optical Materials, and physica status solidi a/b.
Short abstract:
Jos Lenders (Deputy Editor of Adv Mater, Adv Funct Mater, and Adv Optical Mater) and Dimitra Gkogkou (Editor for Adv Funct Mater, Adv Optical Mater, and physica status solidi) from Wiley will track important trends and developments in materials science publishing and the Advanced journals program. Together, these journals receive more than 100 submissions every day, and only around 15% make it to publication. So, what do editors do to select the very best papers, and what can authors do to optimize their chances of having their manuscripts accepted? Jos and Dimitra hope to provide insight into these topics as well as some tips for your publication strategy. The talk will further include an update on Projekt DEAL, the “Publish & Read” agreement between Wiley and a consortium of over 700 German universities and research institutes, allowing scientists from those organizations to have access to and publish Open Access in all of Wiley’s journals. Anybody who is enthused about where scientific publishing will go next is welcome to join the seminar and discussion.

Friday, 24 April 2020
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