Just as normal cell types are ultimately derived from stem cells, increasing evidence suggests that human tumors may also arise from cancer stem cells, which have been implicated in tumor development, maintenance, and metastasis. Despite their importance, our fundamental understanding of "tumor initiating cells" remains incomplete, and therapies that target these cells are lacking. To address this need, we are developing new cellular and genetic analysis methods to delineate single-cell developmental states (e.g., CytoTRACE). Our goal is to discover and better understand tumor initiating cells in primary human malignancies in order to improve cancer patient outcomes.

Digital Cytometry

Tissue composition is a major determinant of phenotypic variation and a key factor influencing disease outcomes. Although single cell RNA sequencing has emerged as a powerful technique for characterizing cellular heterogeneity, it is currently impractical for large sample cohorts and cannot be applied to fixed specimens collected as part of routine clinical care. To overcome these challenges, we have developed new platforms for digital cytometry, including CIBERSORTx, EcoTyper, and CytoSPACE. These approaches leverage single-cell RNA sequencing and expression deconvolution, enabling large-scale and spatially-informed cell profiling of complex tissue specimens. We are currently applying these frameworks to address multiple biological and clinical questions of interest across diverse tumor types.