Binder Lab
Crosstalk between leukemic cells and niche cells can happen by cell-to-cell contact, but also via circulating vesicles, e.g. exosomes. Various nucleic acids have been identified in the exosomal lumen, including DNA, mRNAs, microRNAs (miRNAs), and other non-coding RNAs (lncRNAs). These exosomal RNAs can be taken up by neighboring or distant cells and subsequently modulate recipient cells.
Therefore, in this project, we focus our research on the leukemia-niche interaction via exosomes. We hypothesize, that the exosomal cargo from leukemic cells, e.g. microRNA, taken up by niche cells, switches their function towards a pro-tumoral microenvironment and leads to protection from chemotherapy, later resulting in relapse. Little is known what exact exosomal compounds are essential for the reprogramming of the niche, and whether highly aggressive leukemia uses this protection more efficiently.
Tumor derived exosomes are distributed in the peripheral blood and allow gathering of information about the tumor without getting more invasive than a simple venipuncture for a liquid biopsy.
The goal of this project is to establish a liquid biopsy by identifying exosomal markers for niche exploitation, to detect leukemias with a higher risk of relapse as early as at diagnosis. The identified markers will influence the risk stratification of patients and prevent relapses by an early adjustment of therapy.
To discover exosomal cargo differentially expressed in patients prone to relapse, we analyze both primary serum samples as well as patient derived xenograft (PDX) models.
For the PDX approach, we established a liquid biopsy based assay of isolating tumor specific, human exosomes. We are analyzing the isolated exosomal cargo by next generation sequencing, looking for expression differences as well as mutations and novel microRNAs in high risk samples.
Hereby, we will identify biomarkers for high risk leukemia as well as new druggable targets.
