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.

The Ye Lab is interested in how the interaction between genetics and environment affect human variation at the level of molecular phenotypes. To study these interactions, our lab couples high-throughput sequencing approaches that measure cellular response under environmental challenges with population genetics where such measurements are collected and analyzed across large patient cohorts. We have developed novel experimental approaches that enable the large-scale collection of functional genomic data en masse and computational approaches that translate the data into novel biological insights. This approach is used to initially study primary human immune cells in both healthy and diseased patients to understand host pathogen interactions and its role in autoimmunity.

The Bluestone Lab's research is broadly focused on understanding mechanisms regulating T cell activation. Our work has centered on altering the positive and negative co-stimulatory signals that are delivered in conjunction with signals from the T cell receptor during T cell activation. By manipulating positive co-stimulatory ligands, such as B7-1 or B7-2, or negative regulatory receptors, such as CTLA-4 or PD-1, we revealed new mechanisms to promote immunotolerance. In addition, we are studying an immunosuppressive population of T cells known as Tregs. Tregs are essential for preventing most forms of autoimmunity and we are developing strategies to utilize these cells to treat Type 1 Diabetes and other autoimmune diseases. The breakdown of tolerance has been attributed to an imbalance of effector function and immune regulation, specifically defective regulation due to defects in the T regulatory cells (Treg) subset. Thus, multiple efforts have been forged to re-instate that balance in setting such as autoimmune disease and organ transplantation or disrupt it as a means to promote anti-tumor immunity. Recent investigations have focused on Treg instability in the autoimmune and cancer settings, and targeting of the FOXP3 pathway to selectively enhance Treg function. We have also focused attention on novel approaches to understanding FOXP3 activity and delivering specific signals to Tregs to promote Treg stability and function, including the use of novel IL-2 and anti-IL-2 approaches. Finally, we have initiated early clinical trials translating the insights gained from mouse studies to deliver Tregs and IL-2 therapeutically to promote rebalancing of effector and Treg function in autoimmunity and transplantation.

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 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 Tenthorey lab is broadly interested in the mechanics of how the innate immune system is built to withstand the evolutionary pressures of many different kinds of viral infections. One of the most difficult challenges that the innate immune system faces is an evolutionary problem: unlike adaptive immunity, innate immune proteins do not generate sequence diversity within an individual host. Nevertheless, their viral targets have massive evolutionary potential and can rapidly evolve to escape innate immune defense. In response, innate immune proteins evolve rapidly to select counter-mutations that regain defense, which viruses evolve to escape again, in an endlessly repeating evolutionary arms race. How can innate immune proteins possibly compete in these arms races, given that viruses evolve so much faster than their mammalian hosts? What strategies might allow for temporary or even long-term victory? To answer these fundamental questions, we dissect the evolutionary landscapes (the fitness of accessible sequence space around an extant protein) of innate immune proteins and their viral targets to map the possible evolutionary outcomes. We probe the biophysical features that make such landscapes possible, and we use the incredibly rich data to gain mechanistic insight.

The Debnath Lab focuses on the role of autophagy in cancer progression. As part of this, we analyze the effects of both tumor cell autophagy and stromal autophagy on immune regulation in cancer progression using mammary cancer (PyMT) and pancreatic neuroendocrine models (RT2-PNET). We also work on fundamentals of the autophagy pathway and they have discovered new rolls for autophagy in cargo loading into exosomes. These findings provide new perspectives into the non-cell autonomous roles of the autophagy pathway in disease pathology. Both projects include active collaborations to dissect the role of the immune system downstream of autophagy-dependent exosome pathways.

Dr. Young's goal is to better understand the glioblastoma immune microenvironment by studying longitudinal microenvironment evolution and translating these biological discoveries into new therapies for patients with glioblastoma. Projects in the Young Lab use a combination of high-throughput single-cell and spatial analyses from human tissue obtained in the operating room with mechanistic and in vivo experiments from immunocompetent glioblastoma mouse models to explore how resistance mechanisms develop and tumors evade conventional immunotherapies. Currently, their preclinical work has identified IL6 blockade in combination with checkpoint inhibition as a promising strategy for glioblastoma.

A core interest of the Lee laboratory is designing next-generation cancer immunotherapeutics capable of reversing the tolerogenic organ-specific tumor immune microenvironments associated with metastatic solid tumors, focusing on using preclinical models and patient-sample directed research on difficult-to-treat sites such as liver and bone metastases.�

The Cyster Lab������studies������cell migration and communication, antibody responses, lymphoid tissue biology and mucosal immunology. Major goals include: 1) decipher the guidance cue code controlling leukocyte migration and interactions during immune responses; 2) characterize selection events and niches required for induction of long-lived and high affinity antibody responses; 3) define the dynamics of antigen encounter and immune responses at barrier surfaces. Some projects involve studying immune responses to pathogens or tumors while others examine the derangements occurring in lymphomas and autoantibody-mediated diseases. We use the mouse as our favored model system and employ a range of immunological techniques as well as real-time intravital 2-photon microscopy, biochemical approaches and metabolite quantitation with mass spectrometry. As well as wet-bench researchers, we also seek individuals with computational biology training who are interested in projects involving scRNAsecell dynamics in tissues.

The Moslehi Lab is a basic and translational research laboratory focused on signal transduction in the myocardium and vasculature. Our clinical and research interests fall under the burgeoning field of cardio-oncology. In the past our group initially defined new clinical syndromes of immune checkpoint inhibitor (ICI)-associated myocarditis and other ICI-associated cardiovascular toxicities, including pericarditis and vasculitis. Our interest in "cardio-immunology" has recently expanded to other inflammatory cardiomyopathies, including giant cell myocarditis, acute cellular rejection (ACR) following cardiac transplantation, and other forms of myocarditis.

The Gardner Lab has both a clinical focus in transplant surgery as well as a basic science focused Immunology lab in the UCSF Diabetes Center. Fundamentally, we are interested in understanding the basic mechanisms of self-tolerance in the adaptive immune system, and how characterizing that biology might eventually translate into improved therapeutics in autoimmunity, transplantation, and tumor immunotherapy. In particular our lab focuses on the biology and function of a unique population of dendritic cells expressing the Autoimmune Regulator (Aire) gene, and we have shown these cells to be potent inducers of immunologic tolerance.

With over sixteen years of expertise in cancer and immunology, I have led projects focusing on cancer development, metastasis, and the tumor microenvironment. My research delves into the molecular mechanisms driving metastasis and tumor-host interactions.�