Ruprecht-Karls-Universit├Ąt Heidelberg
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Gaiser0118 - Scientist (f/m) / PhD position
Project no:
Gaiser0118

Project leader:

Project supervisor:
Gaiser, Timo
Application deadline:
31. Jul 2018
Start of PhD project:
1. Sep 2018

Project description:

Title:
Examining long-term response in Trastuzumab-treated metastatic gastric- or gastroesophageal junction cancer patients via molecular HER2 surface and pathway analyses: MetGaP
Summary:
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 a highly modern multiplex interphase Fluorescence in-situ Hybridization (Mi-FISH) to study copy number alterations (gene amplifications and deletions) at a single-cell level for multiple gene targets in the same cell. By performing MiFISH two points will be clarified. (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.
References:
1. Single-cell genetic analysis of clonal dynamics in colorectal adenomas indicates CDX2 gain as a predictor of recurrence. Fiedler, D., Gaiser T et al. Under Review International Journal of Cancer (pdf-File available on request)

2. Aneuploidy, TP53 mutation, and amplification of MYC correlate with increased intratumor heterogeneity and poor prognosis of breast cancer patients. Oltmann J., Ried T. et al. Genes Chromosomes Cancer. 2018 Apr;57(4):165-175.

3. The Evolution of Single Cell-derived Colorectal Cancer Cell Lines is Dominated by the Continued Selection of Tumor Specific Genomic Imbalances, Despite Random Chromosomal Instability. Wangsa D, Ried T et al. Carcinogenesis. 2018 May 23.

4. Phylogenetic analysis of multiple FISH markers in oral tongue squamous cell carcinoma suggests that a diverse distribution of copy number changes is associated with poor prognosis. Wangsa D, Heselmeyer-Haddad K. et al. Int J Cancer. 2016 Jan 1;138(1):98-109.
Methods that will be used:
Immunohistochemistry, Multiplex Interphase Fluorescence in-situ Hybridization (Mi-FISH), Next-generation sequencing, DNA, RNA preparation.
Cooperation partners:
The project is part of a Krebshilfe project. The grant is currently under evaluation by the Krebshilfe. However this Ph. D. project here will be performed independently of the commitment of the Krebshilfe. Parts of the experimental work will be performed at NIH (Porf. Dr. Thomas Ried, M.D. Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA). Prof. Dr. Dr. h.c. Niels de Jonge, group leader at the Leibniz Institute for New Materials is also part of the consortium.
Personal qualifications:
The applicants should possess a strong interest in cancer research, molecular or cell biology. Knowledges in bioinformatics or related areas are also beneficial. He is fluent in German and English and solves problems on-site with self-initiative and are oriented. He is also willing to spend parts of the project abroad (Bethesda, USA).
Keywords:
Cancer research, genetics, intratumoural heterogeneity, Fluorescence in-situ Hybridization, NGS