ImmunoX Faculty Directory

The Faculty Directory highlights the diverse community of faculty engaged with the Bakar ImmunoX Initiative. Use the filters to explore areas of expertise, connect across disciplines, and learn more about the people advancing immunology research and training at UCSF.

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Microbial Pathogenesis and Infectious Diseases
Leadership Committee
Anita Sil
The Sil Lab studies the fungal pathogen Histoplasma capsulatum, which is a soil organism that can infect and colonize cells of the innate immune system after inhalation into mammals. Their research is driven by two key questions. First, how do cells sense temperature and make a developmental switch from the soil to the host program? They focus on temperature because it is a sufficient signal to recapitulate the morphologic switch bettheyen Histoplasma filaments (the soil form) and yeast (the host form) in culture. This question is critical to understanding the basic biology of Histoplasma as theyll as a number of closely related fungi such as Blastomyces, Coccidioides, and Paracoccidioides, each of which is a ubiquitous pathogen of immunocompetent hosts in endemic areas. In fact, one of the fascinating evolutionary questions about these environmental fungi is how regulatory circuits have evolved to link morphology and virulence programs with growth at host is be an entry point to broader studies of host-fungal interactions, since it will define critical developmental changes that promote the expression of virulence traits, as theyll as delineate molecular landmarks that will allow us to stage the interactions of the fungus with host cells. Second, how does H. capsulatum defy the innate immune response to take up residence, often permanent, in immunocompetent hosts? The past ten years have witnessed an exponential increase in their understanding of the innate immune response to microbes, and yet, in the case of fungi, their insight is rudimentary at best. Their studies explore the molecular communication at the host-pathogen interface bettheyen H. capsulatum and the macrophage. H. capsulatum displays extremely robust macrophage colonization, so it is currently the best fungal candidate to probe the Achilles' heel of these powerful innate immune cells and determine novel mechanisms of virulence that have evolved in eukaryotic pathogens.
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Sil
Anita Sil
Professor and Department Chair
Autoimmunity
Member
Judith Ashouri-Sinha
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.
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Sinha
Judith Ashouri-Sinha
Assistant Professor
Infection and Host Defense
Immunogenetics
Leadership Committee
Sara Suliman
The Suliman Lab builds on the foundation of previous human cohort studies to pursue the following directions:From systems biology to innate correlates of TB progression: 1) The lab is following up on candidate pathways identified through systems biology experiments performed on samples from human cohorts of TB progressors and healthy Mtb-exposed counterparts in Sub-Saharan Africa and South America. These genetic and transcriptional profiling studies point to candidate TB risk pathways including sodium/potassium ATPases and tyrosine metabolism enzymes in innate immune populations. The lab is functionally dissecting the roles of these genes using pharmacological inhibitors and CRISPR/Cas9 gene editing of primary human myeloid cells and Mtb infection experiments, followed by analysis of immunological and metabolic profiles, in order to define their roles in TB disease. 2) Point-of-care biomarkers to identify Mtb-exposed individuals at high risk of developing TB disease: Following previous studies on TB biomarkers and COVID-19 diagnostics, the lab leverages international collaborations and systems biology approaches to discover and validate easy-to-use biomarkers to identify individuals at high risk of progression to TB. The studies aim to down-select biomarkers with high accuracy for translation into point-of-care and near-patient prognostic biomarkers in diverse populations for active case finding, including those with other co-infections. 3) T cell immunity to SARS-CoV-2 and Mtb: The Severe Acute Respiratory Syndrome of Coronavirus-2 (SARS-CoV-2) and Mtb are the two leading causes of mortality from infectious diseases globally. Failure to contain SARS-CoV-2 can be a result of the evolution of escape mutations that evade T cell responses. Similarly, in TB, the activation states and memory phenotypes of T cells can determine the quality of adaptive immunity against Mtb. Therefore, the quality and breadth of T cell responses are critical determinants of protection against both pathogens. It is unclear how the co-infections with Mtb and SARS-CoV-2 influence the inflammatory milieu and antigen-specific T cell responses that correlate with protection from progression to TB disease or severe COVID-19. The Suliman lab studies antigen-specific T cell immunity to SARS-CoV-2 and Mtb in the context of co-infection with the two pathogens, evolving SARS-CoV-2 variants, and COVID-19 vaccine rollout.
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Suliman
Sara Suliman
Assistant Professor
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Associate
Hugo Gonzalez Velozo
The Gonzalez-Velozo Lab delves into the molecular mechanisms driving metastasis and tumor-host interactions. It is committed to advancing the understanding of cancer metastasis and the tumor microenvironment, particularly elucidating insights from the tumor-immune interface. The lab's studies integrate diverse disciplines, including cancer research, genomics, molecular biology, immunology, and computational biology. They include the first systematic study of human metastases at single-cell resolution and collaborations in areas such as crosstalk within the metastatic niche, tumor adaptation under stress in metastasis, and cancer immunology. Ongoing projects involve the study of chromatin accessibility at single-cell resolution, combined with single-cell transcriptomics, to define and characterize the gene regulatory networks (regulomes) that foster brain metastases from carcinomas in patients. Additionally, they are working on generating tumor-host assembloids, a novel tool that combines brain organoids derived from iPSCs with tumor organoids from brain metastases, aiming to study in vitro complex cellular circuits while preserving human biology in the system. Their work lies in the conceptual framework that metastatic fitness is intimately linked to cellular circuits and cell crosstalk within the metastatic niche, impacting both the composition and functional states of the tumor microenvironment.
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Velozo
Hugo Gonzalez Velozo
Assistant Adjunct Professor
Brian Graham
brian-graham

The Graham lab's field of research is the study of how host immunity drives pulmonary vascular disease, focusing on the disease schistosomiasis-associated pulmonary hypertension (PH). Schistosomiasis is a major cause of PH worldwide, but how this parasitic infection causes the disease is unclear. We think that some of the pathways that we are uncovering are relevant to other forms of PH more common in developed settings. Our primary approach is using a mouse model of this disease, which lends itself well to investigating how innate and adaptive immunity, and the cross-talk between the two, mechanistically drive pulmonary vascular disease. The pathway we have uncovered includes conventional dendritic cells, CD4 T cells, classical monocytes, and interstitial pulmonary macrophages, expressing cytokines including IL-4/IL-13, CCL2, TSP-1, and TGF-beta. We are now starting to develop protocols for screening humans for this disease in endemic settings, and studying biospecimens from these individuals. We are also studying the role of inflammation in hypoxic-PH and other forms of PH.

John Greenland
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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. Their group has defined novel roles for effector and regulatory T cells, NK cells, and macrophages in the allograft at the time of rejection. The lab has published on the role of immune aging and telomere dysfunction in shaping the alloimmune response. Their 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. As a disease-focused, translational immunology lab based at UCSF Parnassus campus and the San Francisco VA, they are theyll positioned to contribute to ImmunoX.

Peng He
peng-he

The He Lab focuses on understanding how the immune system interacts with diverse cellular and tissue microenvironments during human development and cancer. We integrate single-cell and spatial transcriptomic profiling with advanced computational methods to dissect immune–non-immune crosstalk and gene regulatory programs in situ. A central goal of the lab is to develop computational tools for single-cell spatial atlasing and to build integrated, community-scale reference maps that enable large-scale comparison, data mining, and systematic interpretation of immune states across tissues and disease contexts.

Judith Hellman
judith-hellman

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. These processes result from a complex inflammatory response that is initiated through the innate immune system by interactions bettheyen host cells and microbes or endogenous host factors that are released during injury or cell death. The family of Toll-like receptors (TLRs) recognize different microbial components and endogenous host factors, and are critical in initiating inflammatory responses to infection. They study TLR-dependent pathways expressed by macrophages as theyll as non-conventional inflammatory cells, including endothelial cells, in Inflammatory Critical Illness, focusing on their roles in coagulopathy, vascular permeability, neutrophil trafficking to organs, and organ injury and failure.

Timothy Henrich
timothy-henrich

The Henrich Lab leads a growing interdisciplinary and collaborative research program with a strong focus on translational virology, viral immunology, and infectious disease research; all these projects stem from a passion for challenging or creating paradigms regarding viral persistence and pushing technological envelopes to implement novel strategies to study viral-host-immune interactions across the whole body. Until 2020 their research pursuits focused predominantly on the field of HIV curative strategies, virology, antibody-drug conjugates and stem cell therapies for HIV cure including and pioneering the use of novel technologies to assess viral reservoirs and host immune responses at the single-cell level in many tissues. Since the onset of the COVID-19 pandemic, they have expanded this work in HIV to include SARS-CoV-2 and Human Herpes Viruses with a focus on viral persistence and mechanisms by which viral infections lead to post-acute and long-term sequelae. They are also designing novel high-dimensional digital spatial multi-omic assays to understand viral-immune responses across tissues (brain, heart, gut, lymph node, lung, etc.). Dr. Henrich now leads the UCSF Human Virome Program (U01) project through the NIH Directors Fund to understand the deep tissue virome and immune/inflammatory consequences and founded the Center for Infectious Disease Molecular Imaging to foster development of infectious disease pathogen and immune response characterization in whole-body, non invasive imaging platforms. His lab is involved in looking at mAb activity towards various viruses, granzyme production and T cell activation states using novel PET tracers, among many other approaches.

Michelle Hermiston
michelle-hermiston

The Hermiston Lab is focused on defining the underlying mechanisms in the development of lymphoid malignancies, including leukemia and lymphoma.

Jill Hollenbach
jill-hollenbach

The Hollenbach lab specializes in genetic analysis of the extremely polymorphic human leukocyte antigen (HLA) and killer immunoglobulin-like receptor (KIR) immunogenetic systems. Their work spans the population genetics, evolutionary history, and influence on human health of these complex genomic regions, with particular emphasis on their role in neurological disease.

Chris Hsiung
chris-hsiung

The Hsiung Lab is interested in synthetic gene regulation, combinatorial genetics, and emergent properties in tissue biology. One of our interests is in identifying combinatorial genetic perturbations that elicit systemic anti-tumor immunity.

Peter Hunt
peter-hunt

The Hunt Lab focuses on the causes and consequences of persistent immune activation during treated HIV infection, including its contribution to age-related morbidity and HIV persistence. The lab also has a particular focus on the contribution of asymptomatic CMV co-infection to the inflammatory state and morbidity in this setting, leveraging samples from and contributing to the design of clinical trials on this topic.

Babak Javid
babak-javid

The Javid Lab's research includes study of protective human humoral responses to tuberculosis, as well as molecular mechanisms by which Mycobacterium tuberculosis adapts and evades host immunity. We use animal models, forward genetics and cell biology to investigate the mechanisms by which antibodies may contribute to protection of tuberculosis and the rational design of novel preventative and therapeutic TB vaccines. Our work challenges the decades-old paradigm regarding the relevance of antibody-mediated immunity to tuberculosis. Furthermore, we have identified pathogen-derived mechanisms by which M. tuberculosis adapts to the host environment, including dysregulation of innate and adaptive immunity. Our work combines both hypothesis-driven and agnostic, hypothesis-generating approaches to better understand both the fundamental host-pathogen interaction in tuberculosis as well as identify translationally relevant approaches for novel treatments and vaccines.

Roarke Kamber
roarke-kamber

The Kamber Lab is interested in understanding how macrophages detect and eliminate unwanted cells in cancer and other aging-related diseases. Current efforts in the lab focus on 1) systematically identifying the inter-cellular signaling pathways that enable macrophages to recognize and destroy target cells and 2) engineering macrophages with enhanced capabilities for therapeutic cell clearance. To advance these studies, they combine potheyrful genetic screening approaches to discover molecules that regulate macrophage function with biochemical, cell biological, and in vivo experiments to understand how these components work at a mechanistic level. Their overarching goal is to uncover new biological insights that enable next-generation immunotherapies for currently untreatable diseases.

Bridget Keenan
bridget-keenan

Dr. Keenan is a physician scientist who works in translational cancer research and medical oncology. Her research interests are in studying the mechanisms of response and resistance to immunotherapy, with a focus on gastrointestinal cancers. Her clinical practice is in the Cancer Immunotherapy Clinic, where she leads early phase immunotherapy trials of novel agents including cell therapies, vaccines, checkpoint inhibitors, and T cell engagers.