In B01, R. Thomas will generate pairs of drug sensitive and resistant SCLC models with the goal of performing in-depth molecular studies to identify mechanisms of drug resistance. He will perform high-coverage exome and transcriptome sequencing with the goal of identifying genomic alterations that govern transition to the drug resistant state. Since transcriptional intratumor heterogeneity has been described previously to occur in SCLC with the expression of two orthogonal developmental master programs, R. Thomas will conduct single cell sequencing of the various models in order to link a particular phenotype to the dominance of a given transcriptional profile.