Transcriptomic origins of cancer

Division Of Basic Sciences - Nci

Investigators

Linked publications & trials

Abstract

1. We are currently developing a computational pipeline to do so. We learn each drugs effect on the global transcriptome in a specific cell types (from public datasets like CCLE and CytoSig) and by comparing that with the transcriptional difference between two cell states (say, exhausted T cells versus active T cell states) we attempt to prioritize individual drugs by their potential to reverse cell state. This approach recovers, for instance, IL12 as a potential therapy to alter pre-metastatic niche in lung cancer (previously identified by our collaborator Dr Rosie Kaplan). The work is under progress. 2. We have made substantial progress in analyzing and characterizing the tumor and adjacent normal micro-environment of lung and liver metastasized Adrenal Cortical Carcinoma (ACC) tumors in the NCI cohort. This work is done in collaboration with Dr. Rosie Kaplan. Bulk (80%) of the work is completed and we have found several cell type-specific states in the metastasis and adjacent normal microenvironment (for example, Tip and Stalk endothelial cells, Exhausted T cell, etc) uniquely found in met and adjacent environments that are prognostic of patient survival in TCGA. Intriguingly, our analysis has identified 5 lncRNAs that are broadly over expressed in metastasis and the adjacent tissues across all cellular compartments and are strongly associated with survival in TCGA data. 3. We have launched a new project to characterize cellular states emerging in cancer cell lines after drug treatment, as a way to characterize drug-resistant states and study their properties, regulators and implication in understanding therapeutic resistance and relapse.