The project aims at defining characteristics of persistent transient abnormal myelopoiesis (TAM) and myeloid leukemia (ML-DS) in Down syndrome patients, which are responsible for progression and relapse of the disease.

The results from this characterization will point towards targets for immunotherapy that will help to prevent the progression from a pre-leukemic stage to overt leukemia or may guide novel treatment strategies eliminating AML MRD.The researcher will characterize the expression profile of Down Syndrome patient and xenograft derived primary myeloid leukemia (MRD) cells using flow cytometry-based enrichment and scRNA sequencing to identify novel therapeutic targets for immune-therapy.

Purification of leukemic cells from patient material (TAM-MRD, diagnosis ML-DS, ML-DS-MRD and relapse) and from DS patient PDX mouse models will be performed by cell sorting using leukemia-associated phenotypes (LAIPs).

Next, suitable targets for immune-therapy will be selected, CAR T cells will be generated and tested on ML-DS cell lines and primary TAM/ML-DS cells. Moreover, the organ-on-a-chip 3D platform will be utilized to further evaluate CAR T cell specificity and function, e.g. cytotoxicity, metabolism and proliferative capacity.

Host:

Johann Wolfgang Goethe-Universitaet, Frankfurt am Main, Germany

Supervisor:

Prof. Jan Henning Klusmann 

Duration:

36 months, starting 1-5-2025

Profile doctoral candidate:

Master’s degree in life sciences, other (bio)medical sciences, or related, and practical experience in cell biology, molecular biology, and basic bioinformatics. 

In additional: 

Secondments are planned to the University Hospital München (3 months, Germany, supervisor Marion Subklewe) to generate CAR T cells (mono- and dual-specific) directed to TAM/ML-DS, and to MIMETAS (3 months, Netherlands, supervisor Karla Queiroz) to test the generated CAR T cell therapy in 3D models.