PROJECT 002– SIGNAL TRANSDUCTION AND CHEMICAL BIOLOGY RESEARCH PROGRAM PROJECT SUMMARY/ABSTRACT The Signal Transduction and Chemical Biology Research Program (ST) pursues fundamental cancer research to understand patient- and cancer-specific rewiring of signaling networks and the cell cycle, and how stem/progenitor cell plasticity and heterogeneity contribute to tumorigenesis. This information is used to identify new targets that could be the focus of future drug discovery efforts. Accordingly, an overarching goal of ST is to develop novel and/or test small molecule leads against important drivers of cancer initiation and progression and aid the optimization of `leads' to drugs so that ST discoveries can be translated to the clinic as new cancer interventions. The major role of ST leadership is to ensure communication between clinical investigators, population-based researchers and basic scientists to ensure that potentially translatable findings are explored. ST leadership and Vanderbilt-Ingram Cancer Center (VICC) sponsor meetings and retreats to ensure that communication of the basic science discoveries is robust. Program goals will be accomplished by: 1) performing cutting-edge research in single cell biology, stem cells and signaling networks, to identify key targets that confer selective dependencies in human cancers; 2) promoting cutting edge research in chemical biology and development of new cancer therapeutics; and 3) stimulating interactions among the Program membership to accelerate discovery, mentor junior faculty, foster collaborations with clinical programs, promote technologies such as scRNA-seq, super-resolution microscopy, mass cytometry and PROTACS, and work closely with VICC Shared Resources to develop new instrumentation for cancer discovery. There are 44 program members from 13 departments and four schools with $11M in total peer-reviewed funding and NCI making up 39% ($4.3M). Out of 372 publications, 15% are intra-programmatic and 34% are inter-programmatic. Members also have 115 collaborative publications with investigators at other NCI-designated cancer centers.