Tuomas Tammela

Cellular phenotypic heterogeneity, an important hallmark of cancer, poses a significant hurdle for cancer therapy. The goal of our research program is to understand the biological basis of cell state heterogeneity in solid tumors, in the context of cancer evolution, aging, exercise, and cancer therapies. We study mechanisms of tumor initiation and progression using a combination of proteomic and single-cell genomics approaches, molecular perturbation of gene function, and lineage-tracing and ablation of key cancer cell subsets.  

A central tenet of the Tammela laboratory’s work is the development of genetically engineered mouse models of soft tissue sarcoma, lung adenocarcinoma, and pancreatic cancer. To validate candidate drivers of cancer cell plasticity that emerge from single-cell transcriptomics data, we utilize these living systems that recapitulate human cancer progression, enabling us to visualize dynamics of cell state changes over time and characterize interactions between cancer stem-like cells and their niche. 

These innovative mouse models support functional testing of strategies to reduce cellular heterogeneity in tumors, with approaches including somatic genome editing or CRISPR-mediated gene activation in novel combinations with pharmacologic treatment. The effects of such perturbations on tumor initiation and development can be assessed by classical histopathological and gene expression analyses, as well as by single-cell approaches. These analyses allow us to directly test the impact of depleting highly plastic, stem-like, or niche-forming cancer cells on tumor heterogeneity, and to identify populations that respond to standard chemotherapies or targeted therapies. Knowledge of pathways that maintain phenotypic heterogeneity in tumors can be leveraged to force cancer cells into states that are more sensitive to therapy, enhancing currently limited treatment options and improving outcomes for cancer patients. 

Current Projects: