The Rosen Lab is interested in glycobiology and biological sulfation. The origin of this interest began 30 years ago with our investigation of molecular mechanisms involved in lymphocyte homing to lymph nodes. Over the past 12 years, we have been focusing on the role of the SULFs in cancer, triggered by our finding that one or both SULFs are commonly overexpressed in cancers. Following our initial studies of the SULFs in breast cancer and pancreatic cancer, we have focused on the study of these enzymes in non-small cell lung cancer (NSCLC). Our studies have documented widespread overexpression of SULF2 protein in human NSCLC tumors. Employing a series of tumorigenic lung cancer cell lines, we showed that SULF2 promotes the malignant properties of these cells in both in vitro and vivo assays, including the formation of xenograft tumors in nude mice. We have developed a very sensitive ELISA for SULF2 and have detected the enzyme in human blood. Current studies are directed at determining whether the SULFs could serve as cancer biomarkers in blood or other body fluids.

The Nishimura Lab's research spans basic, translational and clinical research themes. Our clinical/translational projects focus on the use of biospecimens and correlation of morphometry with gene expression and genetic variation in disease-susceptibility. Basic research themes focus-on the regulation of cell-extracellular matrix interactions by integrins, the role of host-pathogen interactions in innate and adaptive immunity in the evolution of fibroinflammatory diseases, the activation and function of TGF-beta������in epithelial-mesenchymal-immune cell interactions and in tumor immunobiology. Current projects include the role of TGF-beta������and inflammation in fibroinflammatory diseases, genetic variation in regulation of TGF-beta������activation in COPD, the role of paracrine TGF-beta activation by mesenchymal cells in the regulation of innate and adaptive immunity, the role of autophagy in lung injury and repair, the role of integrin structure in TGF-P activat

The Gaw Lab focuses on the placental response to perinatal infections and biological correlates of clinical outcomes from a histopathologic and molecular approach. We have three main lines of research in our laboratory- malaria in pregnancy, Zika infection in the placenta, and SARS-CoV2 infection in pregnancy. All areas are unified by the goal of understanding how inflammatory responses at the maternal-fetal interface influence pregnancy outcomes. Our work leverages unique patient samples prospectively collected in endemic regions through successful collaborations, and have great potential to bridge the gap between molecular technologies, human responses to infection, and clinical outcomes. These studies will identify novel mechanisms of pathogenesis and potential pathways for therapeutic intervention to prevent the adverse consequences of these perinatal infections.

The Mellon Lab's resarch is focused on indentifying novel nuclear factors that regulate the transcription of the genes encoding some steroid synthesizing enzymes in the gonads and in the developing nervous system, and studies their mechanisms of action and regulation in normal and diseased gonadal and neuronal tissues. Her laboratory has also recently discovered that neurosteroids, steroids produced specifically in the brain, can directly influence nerve cell growth, development, neuroinflammation, and behavior. Working in conjunction with the Wolkowitz Lab, we are working to share data with other researchers examining the role of the immune system in cross-diagnostic pathology, and to add neuropsychiatric rating scales to other projects assessing immune function in diverse patients at UCSF.

In the Zamvil Lab, our group employs models, including relapsing and spontaneous experimental autoimmune encephalomyelitis (EAE) to study activation and regulation of CNS Ag-specific T cells. In our early work, we demonstrated for the first time that autoantigen-specific T cell clones could cause clinical and histologic autoimmunity. In the last several years, we have applied our experience studying T cell recognition of myelin Ags in EAE and MS to identification of T cells that recognize aquaporin-4 (AQP4), the autoantigen in NMO. Our group provided the first evidence that AQP4-specific T cells exist in NMO patients and in mice. Currently, we are examining those elements that control selection of AQP4-specific T cells and evaluating how the gut microbiome may influence development of AQP4-specific T cells.

The Baranzini Lab's research involves a combination of wet and dry lab approaches to understand the origins of multiple sclerosis and other complex diseases. Wet lab research focuses on the role of host genetics and the gut microbiome in multiple sclerosis. We lead the International MS microbiome study (http://imsms.org/) and actively participate in the International MS Genetics Consortium. Computational research in our lab focuses on data integration approaches to create predictive models for disease progression and management. We are the developers of SPOKE (https://spoke.ucsf.edu), the UCSF biomedical knowledge network.

The Pillai Lab employs a translational systems approach to investigate viral evolution, pathogenesis and persistence, with the goal of developing novel viral eradication strategies. We leverage the extensive biobank at Vitalant Research Institute (VRI) and invaluable collaborations with HIV/AIDS cohorts at UCSF to study the host-virus interface in vivo. We develop and implement unbiased approaches to identify key host immune factors that can be exploited as pharmacological targets and viral disease biomarkers. Our work thus far has elucidated the effects of anatomic compartmentalization on HIV evolution, the role of cell-intrinsic immunity in the antiviral potency of interferon, and the regulation of HIV transcription during suppressive antiretroviral therapy (ART).

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.

The Bapat Lab works to elucidate fundamental relationships in mice and humans to yield novel insights that will translate into transformational therapies for diseases that remain difficult to manage, namely obesity-associated metabolic syndrome ��������� a disease on track this century to become the ���������normal��������� in the US and worldwide. We are currently building an ambitious research program that ranges from basic investigations in mice, to a population scale immune cell atlas in human adipose tissues, to t

The Feng Lab's research focuses on transplant immunology, with a particular focus on determinants of organ tolerance. We are also investigating novel immunosuppressive regimens and pursuing immunosuppression withdrawal in selected liver transplant recipients. By studying the immune profiles of transplant patients who are successfully weaned from immunosuppressants, we hope to predict prospectively which patients may be good candidates for immunosuppression withdrawal.

The Pleasure lab studies autoantibody associated meningoencephalitis. We use a coordinated approach to identify novel autoantibodies and also we study the pathophysiology of known autoantibodies in neurologic disease.

In the Perera Lab we study the mechanisms of autophagy-lysosome activation and how this organelle system contributes to cellular reprogramming in cancer. Autophagy and the lysosome function to capture and recycle diverse cellular and extracellular macromolecules. Our prior studies have identified transcription circuits essential for maintenance of autophagy and lysosome biogenesis in pancreatic cancer and our ongoing work focuses on identifying unique features and functions of these organelles in promoting tumor growth, immune evasion, metastasis and therapy resistance. We use a combination of techniques including organelle purification and biochemistry, immuno-fluorescence imaging, proteomics and metabolomics in cell lines, primary culture systems and genetically engineered mouse tumor models, to address how changes in organelle function in cancer cells and immune cells promote disease.

The Ricardo-Gonzalez lab's overarching goal is to understand how tissue-resident immune cells respond to physiologic and pathologic stimuli and how they can influence changes across multiple cell lineages in barrier tissues.