Ruprecht-Karls-Universität Heidelberg
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Gaiser0119 - Scientist (f/m) / PhD position
Project no:

Project leader:

Project supervisor:
Gaiser, Timo
Application deadline:
30. Nov 2019
Start of PhD project:
1. Jan 2020

Project description:

Examining long-term response in Trastuzumab-treated metastatic gastric- or gastroesophageal junction cancer patients via molecular HER2 surface and pathway analyses: MetGaP
The project focuses on studying genetic heterogeneity on gastric and gastroesophageal junction (GGEJ) adenocarcinomas samples. We hypothesize that higher intratumoural heterogeneity and stronger interactions between HER2 and other signalling receptors of the HER family are responsible for anti-HER2 drug resistance. To address this question the Ph.D. student will apply Next Generation Sequencing Techniques after performing single cell isolation out of FFPE tissue. Both methods are well established in the Mannheimer laboratory and teach-in is guaranteed. Also a very well characterized collective of gastric cancer samples is available from the FLOT4 Study and waits to be prepared.
The following questions will be addressed:
(i) Is there any genetic marker predicting anti-HER2 resistance and (ii) what level of genetic instability is present in gastroesophageal junction adenocarcinomas?
When the project is finished, it will provide key insights into the scientific understanding of the mechanism behind anti-HER2 drug response.
1. Visualisation of HER2 homodimers in single cells from HER2 overexpressing primary formalin fixed paraffin embedded tumour tissue. Peckys DB, Hirsch D, Gaiser T, de Jonge N. Mol Med. 2019 Aug 28;25(1):42.

2. Dynamics of Genome Alterations in Crohn's Disease-Associated Colorectal Carcinogenesis. Hirsch D, …, Gaiser T. Clin Cancer Res. 2018 Oct 15;24(20):4997-5011

3. Perioperative chemotherapy with fluorouracil plus leucovorin, oxaliplatin, and docetaxel versus fluorouracil or capecitabine plus cisplatin and epirubicin for locally advanced, resectable gastric or gastro-oesophageal junction adenocarcinoma (FLOT4): a randomised, phase 2/3 trial. Al-Batran SE, …, Gaiser T, Hofheinz RD. Lancet. 2019 May 11;393(10184):1948-1957.
Methods that will be used:
Immunohistochemistry, Fluorescence in-situ Hybridization (FISH), Next-generation sequencing, DNA, RNA preparation.
Cooperation partners:
The project is part of a collaboration with the Leibniz-Institute for New Materials (Saarbrücken; Prof. Dr. Dr. Niels De Jonge). The Leibniz Institute for New Materials, situated in Saarbrucken, is an internationally leading center for materials research. Chemists, physicists, biologists, and materials scientists shape the work at INM. Its main research fields are Nanocomposite Technology, Interface Materials, and Biointerfaces.
Personal qualifications:
The applicants should possess a strong interest in cancer research, molecular or cell biology. Knowledge in these fields or in bioinformatics are beneficial. He is fluent in German and English and solves problems on-site with self-initiative and are oriented. He is also willing to travel from time to time to our collaboration partner in Saarbrucken.
Cancer research, genetics, intratumoural heterogeneity, Fluorescence in-situ Hybridization, NGS