The Barcellos-Hoff Lab studies the tumor microenvironment, how it is formed during carcinogenesis, and how it mediates the response to radiation therapy. Our particular focus is on the biology of TGFbeta in these processes. We discovered that radiation elicits activation of latent TGFbeta, so much of our studies determine what TGFbeta does in an irradiated cell, tissue, or tumor. Although our primary interest is in mammary gland and breast cancer, we also work with models of glioblastoma and head and neck squamous cell carcinoma.

The Looney Lab is broadly focused on innate immune biology in the lung. Thematic areas include neutrophil and platelet biology as applied to a variety of pulmonary disease states including acute lung injury (ALI)/acute respiratory distress syndrome (ARDS), primary graft dysfunction after lung transplantation, and cystic fibrosis. A major interest is the application of multiphoton intravital lung microscopy as a discovery tool to aid in the study of lung biology, including novel studies on the role of the pulmonary circulation in platelet biogenesis and the hematopoietic potential of the lung. Our overall goal is to identify new mechanisms responsible for lung inflammation and injury and to develop novel therapies to combat lung disease.

The Ansel lab projects span from technology development and basic mechanisms of RNA regulation through in vivo function of miRNAs, lncRNAs and RNA binding proteins in mice and human cells. We study how post-transcriptional regulation shapes immune responses through network regulation of gene expression circuitry in lymphocytes and other immune cells.

The Sirota Lab's long-term research goal is to develop integrative computational methods and apply these approaches in the context of disease diagnostics and therapeutics. We are specifically interested in leveraging and integrating different types of omics and clinical data to better understand the role of the immune system in disease. We are developing computational methods and using them to understand immune tolerance in the context of autoimmune disease and non-response (pregnancy, organ transplant, cancer).

The Anderson Lab's main research interest is to examine the genetic control of autoimmune diseases to gain a better understanding of the mechanisms by which immune tolerance is broken. A major focus of our lab group is a human autoimmune syndrome called Autoimmune Polyglandular Syndrome Type 1 (APS1 or APECED), which is classically manifested by an autoimmune attack directed at multiple endocrine organs. This disease is inherited in a monogenic autosomal recessive fashion and the defective gene has been identified and is called Aire (for autoimmune regulator). Aire knockout mice, like their human counterparts, develop an autoimmune disease that is targeted to multiple organs. Through the use of the mouse model we, along with others, have determined that Aire plays an important role in immune tolerance by promoting the expression of many self proteins in specialized antigen presenting cells in the thymus called medullary epithelial cells. Recently, we have determined that this process is not only critical in the thymus, but also in peripheral lymphoid organs. Current studies in the lab are directed at further understanding the relative contribution of specialized Aire-expressing cells to immune tolerance in multiple autoimmune disease models. In addition to these ongoing studies, our laboratory is also interested the pathogenesis of autoimmune diabetes and in developing other models of autoimmune disease by using transgenic, knockout, and knock-in approaches.

The Feeney Lab studies the human T cell response to infection and age-based differences in the immune response during gestation and infancy. The overarching goal of our research is to better understand how the human infant responds to infection in order to inform the development of vaccines and immune-based therapies. Our main projects focus on human immunity to malaria caused by P. falciparum, a pathogen that has co-evolved with humans for millennia, and the development of immune function during early life. To facilitate these studies, we have developed robust international collaborations, primarily in Uganda, where we have developed significant laboratory infrastructure to study the human immune response to malaria in a highly endemic setting. The Feeney Lab is committed to training scientists from historically under-represented backgrounds, in both the U.S. and abroad.

The Bhattacharya Lab studies the role of monocyte-derived macrophages in tissue fibrosis. Our work started with single cell mRNA sequencing identifying multiple macrophage clusters in injured lung, one of which we found localized to scar and was pro-fibrotic. Our studies are focused on: 1) myeloid-mesenchymal crosstalk; 2) evolution of macrophage identity through transitional states; 3) PDGF signaling. We also work with human fibrotic lung samples in which our findings in mouse were confirmed based on marker analysis. Functional and sequencing studies with human macrophages and fibroblasts are planned. I believe this research is conceptually novel within immunology and also aligns with the translational goals of ImmunoX.

The Lanier Lab invetigates how NK cells distinguish between normal healthy cells and cells that are transformed or infected with viruses. NK cells express a diverse array of inhibitory and activating receptors on their cells surface that bind to ligands expressed on the cell surface of potential target cells. When encountering healthy cells, signals transmitted by inhibitory NK receptors dominate and prevent autoimmunity, whereas the loss of ligands for the inhibitory receptors or the upregulation of ligands for the activating NK receptors on infected or transformed cells allows NK cells to kill these abnormal cells and secrete cytokine that influence the subsequent response by T cells and B cells. We have developed mouse models systems in which key signaling molecules such as DAP10 and DAP12 have been ablated to explore the physiological role of these NK receptors in resistance to viral infections (cytomegalovirus, poxviruses, and influenza) and primary tumorigenesis.

The Akassoglou Lab studies mechanisms of neurovascular regulation of inflammation and tissue repair. Our research focuses on identifying the molecular and cellular interface that blood proteins utilize to interact with nervous system cells and change their functions. Our ultimate goal is to target these interactions for therapeutic intervention in neurologic diseases.

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 Eyquem Lab is focusing on engineering T and NK cells to improve their anti-tumor activity in the context of an immunosuppressive tumor environment. We are studying CAR T and CAR NK cell function/dysfunction in immunocompetent mouse models using single-cell analysis and gene editing. We are also developing novel CAR designs, using genome and epigenome editing to better control T cell fate and ultimately overcome or remodel the tumor microenvironment.

The Pelka lab studies the cellular interactions that shape immune responses in human tumors, focusing on how these responses are regulated. Immune cells cannot execute their function in isolation, but require interactions with other immune and non-immune cells. We still only understand a very small number of these communication networks. Using a combination of large-scale genomic analyses and tissue imaging approaches, we have identified hubs in tumor tissues where tumor cells come into close contact with immune cells. By characterizing and perturbing the cells in these hubs, and the gene networks that are turned on in these cells, we aim to uncover novel ways to harness the immune system in the fight against cancer.

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.