Our Projects

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.

Sjögren’s Disease is a common systemic autoimmune rheumatic disorder that primarily affects salivary and lacrimal glands through lymphocytic infiltration and autoantibody-mediated inflammation, resulting in significant morbidity. STAMP will interrogate the tissue and systems biology of SjD using deep sequencing and other cutting-edge technologies, to better understand 1) the pathogenesis of SjD and identify therapeutic targets, and new biomarkers; and 2) disease mechanisms inherent to progression of SjD from non-SjD to SjD, and from “early SjD” to “advanced SjD”.

Tuberculosis (TB), a disease triggered by the bacterium Mycobacterium tuberculosis, continues to be a major global health challenge. Remarkably, only about 5-10% of people exposed to the bacterium will develop active TB during their lives. This suggests that individual-specific factors play a crucial role in determining the risk of evolving from exposure to active disease. Factors influencing this risk include abnormalities in both innate and adaptive immune responses, metabolic imbalances, the presence of other infections or health conditions, and genetic variations that may increase susceptibility to TB. The Suliman research group aims to utilize systems biology methods, such as genome-wide association studies, transcriptional and metabolomic analysis, and the study of expression quantitative trait loci, to generate hypotheses. Their goal is to pinpoint potential pathways related to TB risk and conduct in-depth studies to understand how these pathways contribute to the development of the disease.

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.

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.

OCR has taken over management of all ImmunoX CoProjects. CoProjects are a series of collaborative research initiatives under the Bakar ImmunoX Initiative, aiming to enhance the understanding of the immune system's role in various human diseases. These projects integrate community efforts, utilizing UCSF's CoLabs' advanced technologies and infrastructure, to create detailed immune profiles. CoProjects range from small pilot studies to extensive research efforts, focusing on diverse immune-related diseases. Funded primarily through the Bakar ImmunoX Initiative, these projects foster data sharing and interdisciplinary collaboration, contributing significantly to immunological research and potential therapeutic developments​

Organoids will be studied to better understand the aberrant pathways underlying colorectal cancer and pancreatic cancer, especially with focus on EGFR signaling and anti-EGFR-therapy and mutations in the Ras driver and experimental Ras inhibitors. Blood and normal liver and pancreas will be banked for studies combining epithelial cell organoids with immune cells. Organoids will remain at UCSF.