The Knott Laboratory is interested in a variety of research topics. The lab currently has three main areas of focus.
Single-cell profiling of patient tumors and of mouse models are revealing that many cancers are constituted of communities of genetically and phenotypically distinct clonal lineages. Previously, the Knott Lab has studied how heterogeneity in cancer cell populations affects the metastatic spread of untreated breast cancer.
Currently, the lab is studying how the clonal dynamics within tumors are altered by treatment with standard of care and experimental therapies. Further, the Knott Lab is attempting to identify the molecular mechanisms driving the phenotypic differences between lineages, as they may hint at alternative vulnerabilities for clones that display resistance to an initial treatment option.
Hetero-Cellular Interactions in Tumors
It is now clear that a key to solving cancer is understanding the tumor microenvironment and how it is manipulated by cancer cells to protect them from therapy. Single-cell profiling of mouse models and patient material is allowing us to study different tumor cell populations for their response to standard of care and experimental therapies.
Technologies are also being developed that will allow the direct interrogation of neighboring cell relationships in untreated and treated tissue, to identify the interaction pathways that associate with therapeutic response.
Members of the Knott Lab develop and apply novel technologies to study tumor biology. In the past, we have developed large-scale molecular libraries to perturb gene function in mammalian cells. The Knott Lab has also developed methods that allow tracing of cancer cell lineages throughout tumor development. These tools are currently being optimized and applied to determine how tumor heterogeneity influences drug resistance.
In addition, the lab is using single-cell profiling methods to interrogate mouse models and clinical samples to understand how different tumor cell populations are affected by therapy. The goal is to begin to understand cellular interactions in the tumor by profiling individual cells in intact tumor sections.
Finally, as these experiments produce novel and complex data sets, the lab also commits a significant amount of effort toward the development of computational tools to extract clinically relevant information from these data.