The Puck Lab focuses on genetic and genomic technology as well as cellular immunology to study human immune disorders and models of lymphocyte development. These studies have resulted in discoveries of new gene defects, including BCL11B, CORO1A and others. Noting the better outcomes for infants with severe combined immunodeficiency (SCID) after diagnosis early in life, Dr. Puck conceived and developed newborn screening for SCID in DNA extracted from infant dried blood spots. This test, now part of standard newborn screening in all 50 states, uses PCR to quantitate T cell receptor excision circles (TRECs), byproducts of T cell receptor rearrangement in the thymus. Absent or low TRECs identify SCID, and also other conditions with T cell insufficiency. Dr. Puck is also advancing new therapies for SCID, with a clinical trial of lentivirus gene therapy for X-linked and a first-in-human Phase I/II study of lentiviral gene therapy for Artemis deficient SCID.

The Raffai Lab investigates the biology of atherosclerosis. Through our studies, we strive to develop a more profound understanding of the immune system's participation in vascular wall inflammation and atherosclerosis. Our long-term goal is to develop approaches to control the immune systems participation in atherosclerosis initiation and progression. Furthermore, we seek to harness anti������ inflammatory and tissue-remodeling properties of the immune system to promote atheroma stabilization and its regression as new treatments for cardiov

Dr. Raja is the Director of the UCSF Immunogenetics and Transplantation Laboratory (UCSF-ITL). The ITL laboratory is a core HLA typing lab for Immune Tolerance Network, a research cooperative focused on the development of therapeutic approached for asthma and allergy, autoimmune diseases, type 1 diabetes and solid organ transplantation that lead to immune tolerance. Our current research centers on three themes: 1) to understand the basis of alloimmuneresponse in clinical transplantation to identify acceptable mismatches and tolerable donor-specific HLA antibodies, which will help designing functional histocompatibility matching for better transplant outcomes; 2) to understand the functional polymorphism of immunity related genes (HLA, KIR, KLR, FCGR) in human populations and impact on infections, tumor transformation, autoimmune diseases, pregnancy success and allogeneic transplantation; 3) to understand the complex relationship between polymorphic Natural Killer cell receptors (KIR receptors) and HLA class I ligands and the influence on human disease and transplant outcomes.

The Rajkovic Lab investigates the genetic underpinnings of the formation and differentiation of gametes and reproductive tract, their role of these genes in human disease, embryo lethality and origin of heritable human disorders. More specicifally, their lab studies transcriptional regulation of ovarian follicle activation and oocyte survival and how these processes are essential to produce healthy egg. Whole genome human studies in their laboratory discovered that DNA damage repair genes such as MCM8 and MCM9 are mutated in women with infertility and the lab is exploring the link bettheyen DNA damage repair genes with infertility phenotypes and accelerated overall aging, as theyll as the effect of these genes on the overall health of offspring and genesis of structural birth defects. These and other studies indicate that many of the reproductive disorders are developmental in origin.

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.

The Roan Lab studies how intracellular and extracellular factors in the tissue microenvironment can affect infection by HIV, mucosal immunity, and reproductive health. They have demonstrated that genital and rectal fibroblasts, amongst the most abundant cells of the mucosa, potently increase HIV infection of T cells through at least two distinct mechanisms: promoting viral entry, and altering the cellular state of T cells to render them more permissive to viral replication. To characterize the molecular basis of how intrinsic and extrinsic perturbations can render some subsets of CD4+ T cells more susceptible than others to HIV infection, they are using a variety of global gene expression analysis approaches, including CyTOF and RNA-seq. These approaches are also being used to characterize the HIV latent reservoir and the nature of viral rebound upon antiretroviral treatment interruption. Another research interest in the lab is to understand how factors in seminal plasma affect reproductive health and susceptibility to sexually transmitted diseases.

Jeroen Roose is a tenured Principal Investigator and Vice Chair of Anatomy at the University of California, San Francisco. He is also a co-founder of UCSF's Bakar ImmunoX Immunology Program and co-lead of UCSF's AutoIPI (AutoImmunoProfiler). The Roose lab focuses on understanding cell fate decisions driven by cell-cell interactions and signaling pathways, in the context of cancer and autoimmune diseases. Dr. Roose also runs an Organoid disease to biology unit connected to UCSF's CoLabs. There is a rich training environment for staff, students, postdocs, and fellows in the established infrastructure of the Roose lab and the programs it is connected to.

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 Rosenblum Lab's central focus is to understand how the immune system is regulated or controlled in peripheral tissues and how this knowledge can be exploited for therapeutic benefit. To this end, we currently have two areas of active investigation: 1) Understanding how regulatory T cells (Tregs) control immune responses outside of lymphoid organs and 2) Understanding the 'alternative' functions of Tregs in peripheral tissues. Because of its complex immunological properties, its accessibility, and potential for clinical translation, the skin is the model peripheral tissue that we primarily focus on. Approximately 50% of our research employs a reductionist approach, utilizing transgenic animal models to ask fundamental questions of how the immune system functions in skin (and other peripheral tissues) at both the cellular and molecular levels. The other half of our work focuses on doing functional immunology with human tissue, human blood and humanized mice.

In the Roybal Lab we harness the tools of synthetic and chemical biology to enhance the therapeutic potential of engineered immune cells. We take a comprehensive approach to cellular engineering by developing new synthetic receptors, signal transduction cascades, and cellular response programs to enhance the safety and effectiveness of adoptive cell therapies. We also study the logic of natural cellular signaling systems, and the underlying principles of cellular communication and collective cell behavior during an immune response.

The Rutishauser Lab's goal is to characterize the regulation of human CD8+ T cell differentiation in response to viral infections and vaccination across the lifespan. Our lab is focused on three complimentary areas of study: 1) exploring the CD8+ T cell-intrinsic and -extrinsic mechanisms that regulate HIV-specific CD8+ T cell dysfunction/exhaustion; 2) defining the transcriptional and epigenetic basis for the altered T cell receptor-driven differentiation of fetal na������ve CD8+ T cells; 3) applying systems immunology approaches to assess longitudinal human immune responses to infection and vaccination using

The Saba Lab's research is focused on the role of sphingolipid metabolism in development, health and disease. We are particularly focused on the biology of the bioactive lipid metabolite sphingosine-1-phosphate (S1P) and the key enzyme responsible for its irreversible metabolism, S1P lyase, having cloned the latter from budding yeast years ago. We showed previously that a tiny population of dendritic cells harbor the S1P lyase activity that generates the S1P gradient needed for T cell egress. This discovery demonstrates a new role for thymic dendritic cells independent of their role in central tolerance. Although S1P lyase expression is higher in thymic epithelial cells (TEC) than in any other cell type of the body, this compartment of S1P lyase has no impact on T cell egress from the thymus, which raises important questions about the function of TEC S1P lyase. 2) S1P lyase in colitis and the gut microbiome. We showed previously that S1P lyase plays a critical role in reducing colitis risk through microRNA-mediated signaling involving STAT3 and NFkappaB inflammatory signaling hubs. We are currently exploring the impact of dietary and endogenous sphingolipids on the gut microbiome and dysbiosis. 3) S1P lyase and immunodeficiency. We recently reported a newly recognized inborn error of metabolism caused by inactivating mutations in SGPL1, which encodes human S1P lyase. We have named the condition sphingosine phosphate lyase insufficiency syndrome (SPLIS). There are many disease features, and mortality in the first decade is nearly 50%. Most if not all patients exhibit T cell lymphopenia, but some also have B and NKT cell deficiencies and low immunoglobulin levels. We are interested in fully characterizing the immunological status of SPLIS patients, leveraging their T cell lymphopenia in newborn screening strategies, and using immunological biomarkers including absolute lymphocyte count as disease biomarkers. The latter can be used to monitor responses to gene therapy and cofactor supplementation approaches we are developing to treat SPLIS patients.