Open Positions for Postdoc and PhD students for Translational Oncology Lab at the new Translational... (# of pos: 2)

Translational Oncology Lab focus on translational cancer research through combining basic with (pre)clinical therapy research. The main focus is on lung cancer and then especially Small Cell Lung Cancer (SCLC).

About the Project:

The research group is trying to identify critical genetic changes that drive the onset of SCLC and they also make use of genetically- engineered mouse models (GEMMs) that closely mimic human SCLC for functional genomics and preclinical therapy studies. However, current SCLC models such as cultured clonal tumor cell lines and GEMMs poorly represent the complex genetic heterogeneity of human SCLC. In order to address this, they formed an expert panel of clinicians and basic scientists to collect primary SCLC biopsy together with follow-up therapy resistant secondary biopsies from the same patient, were propagated as Patient Derived Xenotransplants (PDXs) in recipient immune-compromised mice. This already led to the creation of a panel of SCLC PDX models, which we will use as primary tool to study the role of SCLC heterogeneity in (chemo) therapy response and evasion of adaptive and innate immune response against SCLC.

Main Responsibilities:

The main research project that the Postdoc and PhD student has to perform will therefore be:

- Fully characterize the cellular heterogeneity in PDX SCLC by genetic analyses, specific growth and marker characteristics, as well as comparative genomic sequencing of individual PDX samples via Next Generation Sequencing. Whole exome and transcriptome sequencing should reveal differences in genomic mutations and (mutated) transcript patterns between primary and relapsed, therapy resistant, SCLC.

- Analysis of (epi) genetic factors involved in formation of tumor heterogeneity in in vitro and in vivo models for SCLC. For this we developed a lung cancer metastasis model in mice using with fluorescently labelled SCLC cells for following Epithelial-Mesenchymal and Mesenchymal-Epithelial transformation.

- -Create SCLC PDX models in humanized mice background. Immune compromised mice will be transplanted with either Peripheral Blood Monocytes from patients or human embryonal Hematopoietic Stem Cells to reconstitute a full human adaptive immunity in these mice This enables us to follow growth of heterogeneous human SCLC in a reconstituted human immune environment

- Performing preclinical immunotherapy experiments against SCLC. First immuno therapy experiments will be carried out to the test if immuno-editing efficacy changes, induced by immune checkpoint blockade effectors, are linked to nature and content of neoantigens in every individual SCLC lesion.

Background:

- Required background for both Post Doc and PhD students are; Molecular Biology, Cell Biology, Cancer Biology, Immunology

Experience:

- Candidates need to have the necessary research experience and capacity to perform independent experiments. Both Post Doc and PhD student candidates should have a good academic background, be very motivated and willingness to perform creative innovative research.

- Candidates are not expected to be experienced in all fields combined above but one suffices. Especially an immunologist is very welcome.

- All candidates must have an affinity to work with animals.

For further information and applications, please contact:

Prof. Dr. Ralph Meuwissen

Basic Oncology Department, Institute of Health Sciences

Ege University Translational Respiratory Research Center, EgeSAM

Address: Ege University Campus, Bornova, Izmir, 35040, Turkey

Mobile Phone: +905435756370

E-mail: [email protected] ; [email protected]