Effective targeting chemo-resistant subclones identified by single cell transcriptomics for the treatment of sarcomas

Most child, adolescent and young adult (AYA) sarcoma patients achieve clinical remission with a “one-size-fits-all” chemotherapy approach based on histo-type. Almost one third will relapse and most will die of cancer. There is an urgent need for accurate assays which predict relapse. Longitudinal studies reveal minor cancer subclones at diagnosis which survive early chemotherapy, later leading to relapse. The precision of single cancer cell RNA sequencing (scRNA-seq) has provided unprecedented resolution to uncover the transcriptomic features of these minor subclones. At Children’s Cancer Institute we have established the high-throughput droplet-single cell sequencing platform and have performed proof-of-principle experiments comparing osteosarcoma samples before and after chemotherapy, which indeed revealed enrichment of chemoresistant clones with sensitivities to drugs not normally used in that disease. Our study combines cutting edge scRNA-seq and whole exome sequencing (WES), advanced bioinformatics, large public datasets, and unique clinical resources to address fundamental questions about the impact of chemotherapy-resistant subclones on individual patient outcomes.

Techniques and key outcomes /learnings:

The Higher Degree Research Candidate will master cutting edge cellular and molecular techniques to test hypotheses that changes in genomic and transcriptomic patterns among residual malignant cells in the early phases of chemotherapy indicate subclonal selection for chemoresistance and relapse in patients, some techniques will include: 

1. Single cell RNA sequencing and development of drug combinations.
2. Forward genetics using gene overexpression, knockdown and knockout.
3. Cellular and molecular techniques including flow cytometry, RT-PCR and immunoblotting.
4. Experience in working with patient-derived xenograft models of sarcoma.
5. Bioinformatics.

How to Apply

Express your interest by emailing Associate Professor Belamy Cheung at bcheung@unsw.edu.au. Include a copy of your CV and your academic transcript(s).