This project aims to develop ex vivo immunocompetent bone marrow (BM)-acute leukemia MRD 3D models, that mimic AML MRD in the patient and that will enable discovery of novel therapies targeting AML MRD, while also allowing for identification of treatment responsive patient subsets.
The researcher will make use of the by MIMETAS developed microfluidic 3D tissue culture plate called the OrganoPlate, which is a unique patented technology that enables precise, barrier-free definition of culture matrices and cells in 3D, supporting cell-cell interactions and unprecedented imaging and quantification. The researcher will reconstitute the acute leukemia BM on the Organoplate by addition of patient-derived AML cells combined with other relevant cellular BM niche components, immune cells and the cellular matrix. Then, the reconstituted leukemia BM will be applied in drug response studies.
Results on development, progression, phenotype and kinetics of AML MRD in this 3D model will be compared with data obtained using ex vivo culturing methods, PDX leukemia mouse models and the patient. Hits and relevant genes/pathways identified within the network will be validated in the developed 3D MRD models for efficiency to eradicate AML MRD by CRISPR-Cas9 gene targeting and by targeting with compounds and immunotherapy.
Host:
MIMETAS, Oegstgeest, The Netherlands
Supervisor:
Karla Queiroz
Duration:
48 months, starting 1-5-2025
Profile docatoral candidate:
Master’s degree in life sciences, bioengineering, other (bio)medical sciences, or related, and practical experience in cell biology, molecular biology, and standard cell culture.
In addition:
The researcher will have secondments at the Johann Wolfgang Goethe-Universitaet to learn how to validate a hit by CRISPR-Cas9 (3 months, Germany, supervisor Jan Henning Klusmann), and at the Amsterdam UMC (2 months, Netherlands, supervisor Jacqueline Cloos) to investigate the clinical relevance of the developed 3D MRD models.