High-dimensional profiling of the inflammatory component of human diseases
High-dimensional profiling of the inflammatory component of human diseases
A major focus of the lab is to understand how inflammation contributes to human disease pathogenesis and how immunotherapy agents can help modulate disease pathogenesis.
To do this, we built—together with interventional radiologists, surgeons and pathologists—a cutting-edge tissue pipeline to collect relevant clinical samples at different times during the course of human diseases. We also built a platform to collect surgically resected tumor lesions at different times after exposure to different immunotherapy agents and combination therapies.
We use high-dimensional technologies to map the cellular and molecular composition of lesions as well as the spatial organization of these cellular and molecular compartments. The deep profiling data is paired with multiplex measurements of the blood borne factors that control systemic immune responses and inflammation using proteomic technologies.
We have also integrated deep immune profiling analyses of tumors into several neoadjuvant Phase I Cancer clinical trials via TARGET (provide a link to target), a new program for adaptive clinical trial design, where early cancer lesions naive of treatment are exposed to different immunotherapy strategies prior to surgery, enabling deep profiling of the surgical lesions that respond to or resist immunotherapy.
The goal of these studies is to generate hypotheses on disease drivers, which will be tested in reductionist models to probe disease causality as well as identify molecular response or resistance to therapies. We are using these approaches to investigate different human cancers including Non-Small Cell Lung Cancer (NSCLC)[1-4], Hepatocellular carcinoma (HCC)[add ref.] and colorectal cancer (CRC) as well as inflammatory diseases such as inflammatory bowel diseases (IBD)5 and atherosclerosis6.
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