The Zikherman Lab is interested in understanding how autoreactive B cells, despite chronic antigen engagement of the B cell receptor, are restrained from inappropriate activation and differentiation. We are interested in how this process is disrupted in autoimmune disease, and how tolerance mechanisms can be harnessed to treat autoimmunity. To do so, we are taking advantage of novel reporter mice in which autoreactive B cells are fluorescently marked (Nur77-eGFP BAC transgenic line). Current funded projects include dissecting the distinct roles of the IgM and IgD B cell receptor isotypes in regulating immune responses by autoreactive B cells. More recent work is focused on defining how Nur77 and related orphan nuclear hormone receptors function selectively to restrain activation of chronically antigen-activated B cells.

The Carnevale lab focuses on developing cell therapies for cancer treatment. They develop and harness the power of different unbiased CRISPR screening approaches to identify genes that can manipulated to rewire T cells for therapeutic purposes. The Carnevale lab is working to also expand their efforts into engineering the myeloid compartment to synergize with T cell therapies. Their research will be complementary to the mission and other research interests in the ImmunoX community.

Dr. Lin is the director of the Telomere Core in Dr. Elizabeth Blackburn���������s laboratory. In the last 19 years, my research focused on telomere biology and its role in human diseases and risk factors. We have optimized and developed the high throughput qPCR telomere length assay and the telomerase activity assay for unstimulated PBMCs. My team has successfully performed telomere length and telomerase activity on over 150,000 human specimens to over 90 collaborators from 50 institution resulting in over 100 publications. My recent research interest includes the role of inflammation in psychological stress using in vitro culture systems where we discovered elevated Th17 and Treg T cell functions in chronically stressed individuals. We are currently continuing this project u

The Hellman Lab is focused on basic and translational research on sepsis and other forms of inflammation-driven acute organ failure ("Inflammatory Critical Illness"). Sepsis and multiple organ failure are leading causes of death in the Intensive Care Unit. They result from a complex inflammatory response that is initiated by activation ofthe innate immune system by interactions between host cells and microbes or endogenous host factors that are released during injury or cell death. Non-infectious processes can also cause tissue injury, dysfunction, and long-term complications, such as chronic pain, through the activation of innate immune signaling and inflammation. We use������in vitro and in vivo systems to define immunologic mechanisms and to explore immunomodulation in sepsis and in acute and non-acute injury. Current research focuses include understanding the role of Toll-like receptor (TLR) signaling in different cell populations (e.g.: endothelial cells, leukocytes) in sepsis and injury, defining the mechanisms of endothelial activation and dysfunction in sepsis and critical illness, and delineating the immune and functional effects of activation of thd and endovanilloid systems in sepsis, acute inflammation and pain.

The Fahy Lab focuses on investigations of disease biology in airway diseases such as asthma, CF and COPD. Using carefully collected biospecimens from well characterized research participants and a variety of ex vivo analyses and assays, we explore molecular phenotypes of disease with a view to improving precision based treatments. The emphasis of the lab is on asthma and we have a strong interest in type 2 immunity and how type 2 responses differ among patients and drive mucus gel pathology. Image-base quantification of airway mucus plugs and exploration of novel treatments for mucus occlusion of the airways are also areas of active investigation.

The Ashouri lab is focused on understanding how aberrant immune cell signaling disrupts immune tolerance, resulting in autoimmune (AI) disease. We are particularly interested in T cell mechanisms that contribute to the onset of rheumatoid arthritis (RA), a debilitating disease affecting millions. A specific aim of the Ashouri lab is to identify antigen-activated T cells in RA in order to capture and profile arthritogenic clones and elucidate the earliest events in disease pathogenesis. Our work takes advantage of a specific reporter of T cell antigen receptor (TCR) signaling. Tracking the expression of this reporter of TCR signaling in murine and human T cells facilitates our ability to identify and study arthritis-causing T cells before and during RA disease development and addresses the following questions: 1) How are T cells that are relatively deficient TCR signaling able to mediate arthritis development? Our lab uses molecular and biochemical techniques to examine how chronic TCR signaling can enhance T cell sensitivity to cytokine signaling and its dysregulation in disease. 2) How are arthritis causing CD4 T cells initially triggered in disease and to what antigen do these T cells respond? We utilize multi-dimensional and high-throughput technologies including paired single-cell RNA and TCR-sequencing from mouse and human samples with significant potential to identify the TCR specificity, gene expression profile, and signaling networks of cells involved in antigen recognition in RA. Our model system provides a platform to track antigen-specific T cell responses in human diseases in which the inciting antigen is not known and could be broadly applied to other AI diseases, transplant rejection, cancer, and even checkpoint blockade.

At the Nicolas-Avila Lab, we explore the mechanisms by which immune cells contribute to tissue function. Our goal is to develop strategies to enhance organismal health through immunomodulation.

In the Bondy-Denomy lab, we study bacterial anti-phage ���������immune systems��������� (e.g. CRISPR-Cas, restriction-modification systems, CBASS, Gabija, Thoeris, and others). We are focused on basic immunological questions such as how the pathogen (phage) is detected, how it is stopped, how the host knows self from non-self and how phages inhibit and evade these systems. For many years, we have exploited clinical isolates of Pseudomonas aeruginosa and Listeria monocytogenes, which have numerous functional and diverse immune systems. Our group at UCSF has been a leader in the discovery and mechanistic characterization of the bacteriophage response to anti-phage immune systems, which has revealed new paradigms. Most recently, we have discovered families of anti-CBASS and anti-TIR proteins that function by broadly 'sponging' signaling molecules to prevent immunity. This mechanism has not been observed previously in studied of eukaryotic immune systems and suggests th

The Greenland lab is focused on the immunology and cell biology mechanisms that underlie chronic lung allograft dysfunction (CLAD), the primary limitation to long term survival following lung transplantation. Our group has defined novel roles for effector and regulatory T cells, NK cells, and macrophages in the allograft at the time of rejection. We have published on the role of immune aging and telomere dysfunction in shaping the alloimmune response. Our work leverages genomics and bulk, single cell, and spatial transcriptomics, in collaboration with the ImmunoX CoLabs, UCSF Departments of Medicine and Surgery, and collaborators across the globe.�

The Ernst Lab's research includes basic studies of mechanisms of immunity and immune evasion in TB using animal models, and human studies of immunity to TB. Using animal models, we have identified cellular and molecular mechanisms employed by M. tuberculosis to evade recognition and elimination by T cell responses, and have defined the dynamics of cell trafficking, differentiation, and infection in vivo, to identify check points for preventive and therapeutic intervention in TB. In performing these studies, we have discovered unexpected diversity in the phenotypes and functions of the cells infected by M. tuberculosis in vivo and that explain how M. tuberculosis survives and replicates in professional phagocytic cells. In human studies, we have discovered that in contrast to pathogens that employ antigenic variation to evade immunity and cause persistent infection, the human T cell antigens and epitopes of M. tuberculosis are highly conserved, even in strains that diverged from a common ancestor thousands of years ago. We have identified rare antigens of M. tuberculosis that show evidence of diversifying selection, and have initiated studies to test the hypothesis that T cell responses to those antigens are associated with superior protective immunity compared with T cell responses to conserved antigens.

The Phillips laboratory is focused on understanding the dynamic interplay between brain tumor cells and their microenvironment. Specifically, we study how the immune response influences tumor progression and therapy resistance.

The Engel Lab is interested in the complex interplay between bacterial pathogens and host cells. In particular, we study two important human pathogens, Chlamydia trachomatis and Pseudomonas aeruginosa. Our strengths include using multidisciplinary approaches to these studies���������allowing the pathogen to be our tutor. We have utilized bacterial genetics and genetic screens, molecular biology, cellular microbiology, host cell biology with advanced immunofluorescence microscopy, genome-wide RNAi screens, bioinformatics, and proteomics to rigorously understand the mechanisms by which they subvert host cell functions to cause disease. Our current studies focus on the dissection of the Chp/Vfr/ regulatory pathway that regulates diverse virulence factor circuits in P. aeruginosa in determining the bacterial and host determinants involved in the formation of biofilms and spatially localized activation of the innate immune response at the apic

The Baron Lab's������research goals are to combine medical and scientific understanding (Immunology and Virology) to elucidate mechanisms of infectious disease pathogenesis; and to translate this knowledge into new treatments. The majority of our research efforts focus on the study of a major global pathogen, hepatitis B virus (HBV). Over the past years, our laboratory has focused on developing transgenic mouse models of primary HBV infection that mimic key aspects of age-dependent HBV clearance and persistence, in humans, to enable the dissection of immune mechanisms underlying viral clearance or viral persistence. In parallel, we have developed a state-of-the-art bio-repository, and a clinical research infrastructure to provide human samples with which to validate molecular mechanisms defined by our mouse models. Funded projects include studies in the HBV mouse models, as well as a clinical and translational research trial to induce and study effective immunity to HBV; as well as immunomodulatorhuman viral infections and cancers. Our research program spans basic, translational, and clinic research themes. Additional projects studies on fibro-inflammatory diseases including liver and lung fibrosis; as well as immunomodulatory therapies for human cancers, including HCC. Our laboratory provides an excellent environment for studying how very basic and translational research can be successfully combined to advance our understanding of physiology and disease mechanisms. For these reasons, along with our dedication to mentoring the next generation of physicians and scientist, our laboratory has been very successful in attracting and training outstanding students, postdoctoral fellow, and physician scientists.