Universitätsklinkum Freiburg
Prof. Justus Duyster,
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| Research Interest |
Prof. Justus Duyster is head of Medical Clinic for Hematology, Oncology and stem cell transplantation and has a long track record in the field of lymphoma and leukemia research and oncogenic fusion proteins. The Duyster group has previously established a murine bone marrow transplantation model and showed that retroviral NPM-ALK transduction into murine bone marrow leads to a histocytic or plasmocytic disease depending on viral titre. To induce a T-lymhoid ALCL in mice, we currently expressed NPM-ALK in a spatio-temporal manner. We will use this model to study lymphoma stem cells in NPM-ALK driven lymphomas and the eradication of the Lymphoma initiating population. Moreover, our current research involves the signal-transduction and the crosstalk between the DNA-damage stress axis in lymphoma initiation and progression. |
Teresa Poggio
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| Research Interest |
Teresa Poggio received her Master degree in Medical Biotechnology in 2012 from the University of Torino, presenting a thesis entitled “Oncogenic ALK controls hypoxia response and neoangiogenesis in lymphoma and lung carcinoma”. As an undergraduate student she joined Prof.Chiarle’s Laboratory at Center for Experimental Research and Medical Studies (CeRMS), Torino, Italy and she kept working in his group as a Research Fellow until 2016. In 2014 she joined Prof. Chiarle’s Laboratory at Boston Children’s Hospital and Harvard Medical School, Boston, USA, for 6 months where she greatly contributed to ongoing projects. Teresa Poggio has been recruited within the EU-funded ETN ALKATRAS Early Stage researcher (ESR14), starting on August, 1st, 2016. She will join Dr.Duyster and Dr.Illert’s group at Universitaetsklinikum Freiburg, Freiburg, Germany. The main focus of her project aims at elucidating whether therapeutic intervention is capable of eradicating the early lymphoma initiating ALK-positive cell population in a mouse model. |
By lineage- and differntiation-specific expression of NPM-ALK in vivo we were able to establish a mouse model of ALCL closely recapitulating the human disease. T-cell subtyping revealed a heterogeneous ALK-positive lymphoma population with a mixture of very early (CD4/8/25 negative, CD44 positive) up to mature CD4- or CD8-single positive T-cells. Serial limiting dilution transplatation experiments showed that the lymphoma initating cells reside in an early (CD4/8/25 negative, CD44 positive) T-cell population. The main focus of this project aims to elucidate whether therapeutic intervention is capable of eradicating the early lymphoma initating ALK-positive cell population in a mouse model.
Specifically we will aim to: Treat recipient mice that were transplanted with NPM-ALK infected BM cells of CD30 Lck-Cre mice with ALK inhibitors and monitor treatment response by PET-imaging; perform immunophenotypic analyses of the early (CD4/8/25 negative, CD44 positive) lymphoma initating T-cell population; limiting dilution transplatation experiments will elucidate whether ALK-inhibitor treatment canabolish lymphoma develpment in secondary recipient animals; determine the effect of combined ALk and CD30 receptor inhibition in transplanted mice on eradication of the lyphoma initating cell population.
Expected Results:
Address important clinical questions towards the curative potential of ALK inhibitors alone or in combination with CD30 receptor inhibition; potential of these inhibitors to eradicate the lymphoma initating and maintaining the cell population.
Planned secondment(s):
Year 1: TissueGnostics (PO#2) – analysis of tissue arrays for protein expression – 1 month;
Year 2: University of Cambridge (B#1) – Analysis of trangenic murine models of ALK-induced lymphoma for the presence of cancer stem cells – 2 months