The Immune Cell Census aims to determine how much variation exists in normal immune systems, and importantly - how much variation exists in even a single person’s immune system at various times. We'll be profiling transcriptomes, epigenomes, and a subset of the proteome at the single-cell level to understand the composition and function of individual immune systems. Funded by the Bakar ImmunoX Initiative and the Chan Zuckerberg Initiative.

SICCA is built upon a 10-year enrollment of patients with signs and symptoms of Sjögren's Syndrome (SS) from 9 research centers in 7 countries over 4 continents into a cohort with well characterized phenotypic features of SS, and a comprehensive biorepository with 3,514 participants with genome-wide genotyping performed on all participants. The overarching goal of the SICCA NextGen study is to generate transcriptome and methylation profiles to explore diversity across subsets of SICCA participants with characterized epigenetic and genetic profiles across cell and tissue types and to explore correlations between omics profiles and signs of severe disease manifestations.

Funded by the National Institute of Dental and Craniofacial Research

The Colorectal Cancer ImmunoPLUS Organoids Project aims to determine how colorectal cancer (CRC) escapes immune surveillance and coopts a tumor microenvironment (TME) to promote tumor growth and metastasis. We are profiling TME cells and transcriptomes of CRC patients at the single-cell level and engineering data-driven, patient-derived organoids co-cultured with autologous immune cells to understand and perturb tumor immune microenvironments. Funded by the Bakar ImmunoX Initiative. 

The Human-Mouse Cancer Translator Project aims to Immunoprofile a series of common and exceptional models of cancer in mice.  Models will be studied in various environmental backgrounds such as variation in diet and age. The goal of the project is to create a rational translation between the classes of immune systems in cancers as revealed in Immunoprofiler and other UCSF datasets. Funded by the Bakar ImmunoX Initiative.

The AutoImmunoprofiler team is analyzing tissue and blood samples from patients with various forms of autoimmune disease to identify autoimmune archetypes that underlie these diseases. Autoimmune diseases being studied include type 1 diabetes, systemic lupus erythematosus,  Sjögren’s syndrome, ulcerative colitis, Crohn’s disease and scleroderma. Initial funding comes from a research alliance with Eli Lilly and Company.

Industry Partners: Eli Lilly, (Open for enrollment)

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.

Industry Partners: Bristol-Myers Squibb, Amgen, Abbvie, Pfizer, Anonymous

The Innate Immunity and Neurodegeneration project aims to investigate the role of microglia and astrocytes in neurodegeneration in a common familial form of frontotemporal dementia (FTD) caused by mutations in the human progranulin (GRN) gene. The brain has long been thought to be an immune-privileged organ, shielded from the peripheral immune system. However, emerging evidence indicates that the brain’s own innate immunity, which consists of microglia and astrocytes, plays major roles in promoting neurodegeneration in the aging brain. In addition, we have ongoing collaborations with other investigators at ImmunoX to determine the role of GRN mutations in peripheral immunity, focusing on autoimmunity dysfunction and immune-mediated tumorigenesis. Funded by the Bakar ImmunoX Initiative.

The goal of this study is to elucidate how in utero inflammation imprints the developing human fetal immune system and alters the composition of the meconium microbiome. We propose to address this question by interrogating the cord blood immune profile and the meconium microbiome in two neonatal cohorts: one of infants born preterm (<34 weeks) and a second of term infants with gastroschisis. 

Funded by the Bakar ImmunoX Initiative

The goal of this project is to delineate at the single cell level the evolution of the developing human immune system through its functional transition from a program of predominant tolerance to one of protective immunity. Our proposal leverages our unique access to and experience with fetal and organ donor tissue to address critical gaps in our knowledge regarding: (1) the relationship between immune cell populations from different tissues within a single donor, (2) the age-dependent maturation of innate and adaptive immune cells during the critical early life window spanning in utero gestation to late childhood, and (3) the role of metabolism in shaping immune cell fate and function across different tissues and developmental stages. These studies are poised to elucidate the development of human immune cellular identities, functional phenotypes and metabolic capacities and dependencies unique to fetal and pediatric tissue, with key implications for understanding and treating infectious, allergic, and autoimmune conditions of early life onset.

Funded by the Bakar ImmunoX Initiative

Our long-term goal is to unravel the mechanisms by which the microbiome influences immunity and immunotherapy responsiveness. We will generate a comprehensive multi-omic dataset featuring longitudinal immune and microbiome data from a healthy cohort and perform integrative analysis to model how the microbiome influence the immune system. Our central hypothesis is that the microbiome is responsible for shaping and priming distinct immune setpoints across the population. These setpoints influence the susceptibility to disease and the severity of underlying pathologies, but also the capacity for the immune system to be modulated through therapeutic interventions. 

Funded by the Bakar ImmunoX Initiative

The aim of this project is to characterize the fetal immune response to malaria and to CMV by performing Cytof and scRNAseq on cord blood cells from already banked from an extremely well-characterized cohort of Ugandan infants. We will broadly examine differences in immune cell populations in cord blood and identify transcriptional changes in response to infection

Funded by the Bakar ImmunoX Initiative

COMET is a multi-institutional study to collect detailed clinical, laboratory, and radiographic data in coordination with biologic sampling of blood and respiratory secretions and viral shedding in nasal secretions in order to identify immunophenotypic features of COVID-19 -related susceptibility and/or progression in order to generate hypotheses for effective host-directed therapeutic interventions.

Funded by the National Institute of Allergy and Infectious Diseases

The Chronic Viral Infection project aims to evaluate the immunological context of anti-viral and anti-tumor immune response by assessing local (liver) and peripheral (PBMC) immune repertoires in uninfected patients, patients with active viral replication (HBV, HCV) and patients with drug-induced viral suppression and/or clearance in the presence and absence of liver cancer. We'll be profiling transcriptomes and a subset of the proteome both in bulk and at the single-cell level to identify novel targets for therapy to augment viral clearance in chronic viral infection and control of liver cancer through immunomodulation. Funded by the Bakar ImmunoX Initiative.

Our central hypothesis is that granulomatous inflammation of sarcoidosis is orchestrated by a complex interaction of lymphocytes and innate cells reacting to antigenic stimuli of unknown etiology. Leveraging our cohorts, our study aims to determine the patterns of lymphocyte and innate cell differentiation trajectories and TCR/BCR diversity regulated by flares of sarcoidal granulomatous inflammation using single cell CITEseq and measurement of the TCR/BCR repertoire. We will also decipher cell-cell communication between circulating lymphocyte subsets and innate cells in longitudinal samples taken over the disease course from sarcoidosis patients and determine chromatin-accessibility signatures in purified CD4 T cells from patients representing each clinical phenotype and will perform a meta-dimensional analysis to identify biologic blood markers that predict the clinical course in each cohort. and perform prediction modeling to find those markers that carry the most prognostic importance with the long-term goal of moving biomarkers into clinical practice.

Funded by the Bakar ImmunoX Initiative