This team seeks to provide an understanding of the mechanisms regulating the tumor-host interaction interface and their effects on host immunity, tumorigenesis, and therapeutic response. The aim is to uncover molecular and biophysical signatures of tumor interactions with its microenvironment through expertise of team members: development of novel

1) cancer organoid models,

2) microfluidic devices for precise biophysical measurements in organoid or single-cell biological systems,

3) proteomic and lipidomic methods for characterizing host immune signaling and spatiotemporal responses, and

4) dynamic metabolic profiling methods in cancer models. Information encoded in organoid transcriptomes, proteomes, interactomes, surfaceomes, lipidomes, metabolomes, metabolic flux, secretomes, and biophysical properties will be integrated to uncover drivers of tumorigenesis and potentially new therapeutic targets.

These analyses will be facilitated by the development of a series of sensitive and accurate mass spectrometry (MS)-based methods for dynamic protein analyses and metabolite imaging in 3D organoid systems. The design of thermal proximity coaggregation MS for human and mouse organoid systems will allow the team to monitor assembly/disassembly of protein complexes at a systems-level and discover which functional protein units participate in response to cell-intrinsic or -extrinsic factors or to conventional, targeted, and emerging therapies. Rapid organoid responses to a changing microenvironment will be further modeled and analyzed by developing a chemostat that will allow real-time imaging and high-throughput secretome and metabolome analyses. A major focus of the team will be on High-Grade Serous Tubo-Ovarian Carcinoma (HGSC), a prevalent and deadly form of cancer. Multi-omic analyses and biophysical measurements will be used to investigate genotypically-distinct organoids and their impact on HGSC evolution, communication with the microenvironment, and therapeutic sensitivity.