The UCSF Immunoprofiler Initiative coordinates the handling of valuable human biopsy samples taken from cancer patients, and performs a series of tests for immune composition, immune cell gene expression, and immune interaction biology. We propose that cancers are discrete forms of immunopathologies. By understanding the nature of the immune response, we will determine how to treat cancers and provide new targets for the next round of immunotherapies.

AutoImmunoprofiler is a consortium project with the objective to profile a range of autoimmune diseases using a combination of proteomic, transcriptomic, epigenomic, and structural analyses. Emphasis will be on freshly collected tissue samples with matched peripheral blood samples from select clinically well-annotated patients. Overall goals include to better understand the underlying mechanisms of autoimmune diseases, identify the relationship between diseased tissue and peripheral compartment, elucidate novel pathways and targets for therapeutic intervention, and to guide the selection of patients and indications for existing drugs.

Rheumatoid arthritis (RA) is a chronic, destructive autoimmune disease that targets joints and other organs. CD4 T cells are known to play a key role in the pathogenesis of RA. Yet, how arthritis-causing T cells contribute to disease is not understood since it is difficult to differentiate T cells that have been activated by the inflammatory milieu in the arthritic joint from those activated through their TCR by autoantigens. Here we propose to take a hypothesis driven approach to studying the antigen-activated CD4 T cells in RA synovial tissue. Additionally, we propose to investigate more broadly all the immune and nonimmune cells present in RA synovial tissue. This will advance our ability to characterize tissue resident cells and infiltrating immune cells expanded in the RA synovium with the ultimate goal to deliver more targeted therapeutics.

The acute respiratory distress syndrome (ARDS) and sepsis are leading causes of death in critically ill patients, yet both are clinical syndromes defined by non-specific signs and symptoms which encompass major clinical and biological heterogeneity. Pre-clinical studies have identified numerous promising therapeutic agents for both ARDS and sepsis, but clinical trials of these agents (with a handful of exceptions, mainly in COVID-19) have been relentlessly negative, in large part due to this aforementioned heterogeneity. The Calfee Lab has identified two molecular phenotypes within ARDS and sepsis, with consistent reproducibility across numerous studies, widely divergent clinical outcomes, and differential responses to therapy. Patients with ARDS and/or sepsis will be classified into the hyper- or hypoinflammatory phenotypes using our validated biomarker-based classifier model, applied to data from cohort enrollment. Subsequent assays will query differences in immunophenotype and metagenomic profile between phenotypes. We plan to apply these approaches in both blood/plasma specimens and tracheal aspirate when feasible, to compare the biologic response in each compartment.