Parallel Molecular and Functional Dissection of Cancer Cell States in Human Solid Tumors

ASPIRE Award (2022-Present)

Tuomas Tammela, MD, PhD; Dana Pe’er, PhD; Rui Gardner, PhD, Memorial Sloan Kettering Cancer Center

Tuomas Tammela, MD, PhD

Dana Pe’er, PhD

Rui Gardner, PhD

Tumors are made up of functionally and molecularly distinct cell states, which can have different abilities to grow, differentiate, develop resistance to treatment, and metastasize. Single-cell genomics has made it possible to study cancer cell states at a large scale, but current approaches are limited in their ability to connect the molecular features of these states with their functional properties. This limitation is generally inherent to all single-cell methods that require cell lysis, as the molecular and functional characterization experiments are necessarily temporally uncoupled from each other. To overcome this, Tuomas Tammela and Rui Gardner have recently developed a novel spectral sorting approach using a bespoke surface marker panel enabling highly multiplexed cell sorting of tumors. This new method enables the prospective identification and simultaneous isolation of cell subsets, which allows the parallel interrogation of their molecular and functional features in the same experiment.

In their collaborative ASPIRE project, Tammela and Gardner will collaborate with Dana Pe’er to apply this new method to primary human lung adenocarcinomas and patient-derived xenograft models to better understand the heterogeneity of cancer within tumors. Using their surface marker panel, tumors from patients will be sorted into their distinct cellular subsets and subjected to single cell genomics analysis. In parallel, the isolated subsets will be subjected to single cell genomics analysis. In parallel, the isolated subsets will be subjected to functional assays to measure growth, differentiation, and metastatic potential as well as responses to different cancer therapies. This study will elucidate intra-tumoral heterogeneity in human lung cancer patients at unprecedented resolution, which holds the potential for translation into new biomarkers and therapeutic approaches.