Translational Tumor Biology using Microfluidics

BIOENGINEERING SEMINAR

Abstract:
Droplet microfluidic approaches offer significant benefits for translational cancer research. In these systems, tiny aqueous droplets (picoliter volumes) surrounded by oil serve as independent assay vessels. Due to the small assay volumes, large-scale screens can be carried out at very high throughput (analyzing hundred thousands of samples in a single experiment), at the single-cell level and/or using limited patient material (e.g. tumor biopsies). We exploit these conceptual advantages in three different research fields:

1.) Screening large immune repertoires to derive anti-cancer antibodies. By co-encapsulating plasma cells and cancer cells into the same droplet, we can select directly for antibodies that specifically bind to (potentially unknown) tumor antigens or for antibodies with (ant)agonistic action on tumor-associated GPCRs and ion channels. Furthermore, the technology can also be used to isolate cytotoxic T-cells with desired specificities.

2.) Personalized cancer therapy. We have recently demonstrated fast and cost-efficient screening of human pancreatic tumor biopsies for their sensitivity to systematic drug combinations (results are available within 48h after surgery at costs of <150 US$), and we successfully identified particularly potent hits that had not been described previously. We now perform complementary studies in mouse models, implement transcriptomic and image-based readouts and adapt the technology for immune oncology approaches.

3.) Massively parallelized genetic assays. We routinely perform single-cell transcriptomics (modified DropSeq), genotypic sorting of single-cells and deterministic barcoding of cellular cDNA (e.g. to analyze the transcriptome of cancer cells under hundreds of different conditions in parallel). These approaches are particularly powerful for analyzing resistance mechanisms in cancer cells.
In parallel, we are highly active in the development of microfluidic hardware (including the construction of instruments), customized microfluidic chips and control software for specific applications and readout systems. Taken together this enables entirely new avenues in translational cancer research.

Bio:
PhD 2004, University of Frankfurt.
Postdoctoral research at the MRC Laboratory of Molecular Biology, Cambridge.
Junior group leader at the Institut de Science et d'Ingénierie Supramoléculaire, Strasbourg.
Group leader at European Molecular Biology Laboratory (EMBL) since 2010.
Group leader in the Molecular Medicine Partnership Unit.

Zoom link for attending remotely: https://epfl.zoom.us/j/338924706