The Binstadt lab conducts research at the intersection of autoimmune disease and cardiovascular disease. Rheumatic diseases including rheumatoid arthritis, rheumatic heart disease, and systemic lupus erythematosus are associated with an increased risk of cardiovascular disease. While inflammation is a critical link between rheumatic diseases and cardiovascular disease, the precise mechanisms controlling this link remain undefined. We are interested in identifying these mechanistic links between autoimmune and inflammatory diseases and cardiovascular disease. Using a pre-clinical model of arthritis and cardiac valve disease, we have uncovered novel roles for myeloid cells, endothelial cells, and a number of immune signaling pathways that drive the development of mitral valve inflammation and fibrosis. You can read more about our research findings here!
The Bold lab focuses on using advanced genetic tools in Mycobacterium tuberculosis to understand the targets and mechanisms of protective immunity in tuberculosis, as well as novel methods by which the bacteria evade immune destruction.
The Campo lab is examining regulatory innate immunity pathways of the early stages of tuberculosis, which can lead to the discovery of new therapies.
Graduate Students and Post Doctoral Fellows in the lab are working on research that is focused in three broad areas: B-cell development in the bone marrow and B-cell acute lymphoblastic leukemia (ALL), the developmental pathway of T regulatory cells, and cancer immunotherapy. View publications here.
The major focus of research in the Fife Lab is on the restoration of immunological self-tolerance for treatment of autoimmunity. Working with T cells, specifically CD4+ and CD8+, the Fife lab is investigating possibilities for a cure to be found for Type 1 Diabetes.
Graduate Students and Post Doctoral Fellows in the lab are working on 3 areas of research: immune cell signaling, immune dysfunction and protein regulation. The lab focuses on how myeloid cells integrate positive- and negative-regulatory signals to achieve tissue-specific functions and drive pathologies from autoimmune diseases to breast cancer. Protein tyrosine kinases, including Lyn and the other Src-family kinases, are modulators of cell sensitivity, and thus cell- and receptor-specific modes of kinase regulation and function are areas of special interest to her lab. View publications here.
The Griffith lab studies the therapeutic potential of apoptotic cell death in the treatment of cancer. The tumor necrosis family member, TRAIL/Apo-2 ligand, is a potent inducer of tumor cell apoptosis, but is non-toxic against normal cell and tissues, suggesting that TRAIL might be administered as an antitumor therapeutic without the side effects seen with other TNF family members, namely TNF and Fas ligand, and traditional chemotherapeutics. The lab is using various gene delivery systems, such as non-replicative viral vectors to administer genes directly into tumors sites in situ. This technology has led to the development of a recombinant, replication-deficient adenoviral vector encoding the full-length TRAIL cDNA (Ad-TRAIL) as a way to induce tumor cell death. Current experiments are investigating the ability of Ad-TRAIL to activate systemic antitumor immunity. Additional studies are investigating the ability of apoptotic cells to influence the immune response. For these studies, we use a number of experimental model of tolerance as well as an experimental model of sepsis.
The Hamilton-Hart lab studies CD8+ T cells with the goal of learning how to manipulate them to elicit the optimal protective immune response to pathogen infection. They are currently working in two different model systems: mice that have been naturally exposed to environmental microbes to gain a better understanding of T-cell function in these mice, and mice exposed to malaria to gain a better understanding of T-cell activity during severe cerebral complications of the disease. View publications here.
There is no approved vaccine for malaria, and there are still many fundamental unanswered questions for malaria immunity. The Hart lab believes many of these unanswered questions lie where innate immunity intersects with the adaptive immune system. Using a basic immunology approach, they collaborate with on-going studies in malaria endemic regions of Africa. Current malaria projects center around understanding the mechanism of antibody mediated immunity and innate regulatory mechanisms (or lack thereof) in pathological immune responses. We use human subject samples primarily for our studies, and we are also developing novel mouse models to better understand in vivo dynamics where needed.
The Hogquist lab is working on research that is focused on positive and negative selection of T cells in the thymus and understanding how persistent viral infections shape the immune system outside of the thymus. The immune response in animals is highly dependent upon the proper functioning of T cells. The hallmarks of T cells that allow them to function effectively and safely are established as the cell develops in the thymus- an organ specialized for T lymphopoesis. Our research is on the molecular mechanisms of these processes. View publications here.
Graduate Students and Post Doctoral Fellows in the lab are working on research that is focused on CD8 T cell responses against pathogens, but we also study CD4 T cells and B cells. We look at the protective immunity by CD8 T cells, the function of Kruppel-like factors in T and B cells and the homeostatic mechanisms regulating naïve T cell responses. View publications here.
The Jenkins lab is working on research that is focused on CD4+ T and B cell activation in vivo by directly tracking antigen-specific cells. The goal of this research is a basic understanding of lymphocyte activation that can be used to improve vaccines and prevent autoimmunity. View publications here.
The main focus of the lab is on development of treatments to repair antibiotic injury to intestinal microbial communities, also known as the ‘microbiota’. The most well recognized complication of treatment with antibiotics is Clostridioides difficile infection. However, the standard treatment for this infection is more antibiotics. In fact, the treatment doesn’t work in many patients and the infection keeps coming back. Our program has developed therapeutic preparations of donor microbiota to treat patients with difficult C. difficile infections; these are commonly known as Fecal Microbiota Transplants (FMT), although we prefer the term Intestinal Microbiota Transplants (IMT). We manufacture IMT preparations as frozen liquid or encapsulated freeze-dried microbiota. Microbiota therapeutics are classified as drugs by the FDA. However, they are clearly different from small molecule drugs and biologics. In fact, these therapeutics belong to an entirely novel class of drugs, which requires building a new pharmacologic discipline. I am intensely interested in all aspects of microbiota therapeutics pharmacology, including formulation, pharmacokinetics, and pharmacodynamics. Our program is committed to support academic trials for a variety of applications. Some of the ongoing work is in the areas of ulcerative colitis, autism, advanced liver disease, and others. Microbiome research is applicable to many areas of medicine and we are happy to collaborate with clinical investigators. A more complete description of the program can be found here.
Influenza A virus (IAV) represents a major global health burden. The virus is able to escape seasonal immunity requiring yearly vaccination and the threat of novel pandemics loom. Therefore, continued understanding of the host-pathogen interactions and protective immune responses are critical for the development of therapeutic interventions and protective vaccines. We aim to address fundamental questions in virology and viral immunology that have been difficult to dissect using conventional approaches. We generate novel recombinant viruses, virus host model systems, and animal models to probe the antiviral responses. We are also interested in how viruses evolve in the face of antiviral immune responses and how viruses make jumps into new species. To study this we use a newly developed model system to track viruses within both the reservoir and host, where we can perturb key components of the immune system in the host.
The focus of the Lipscomb lab is to mechanistically describe the immunoregulatory network(s) that govern the differentiation and function of antigen-presenting myeloid cells both under steady-state and disease settings. In addition, his laboratory employs the use of novel biomaterials to generate organoids for tissue restorative therapies, with the chief aim to resolve chronic autoimmune disorders and immunodeficiencies.
The Masopust lab studies T cell responses to viral and bacterial infections & candidate vaccines to help understand the development of immunological protection from re-infection. They employ a combination of flow cytometry, immunohistochemistry, intravital microscopy, cellular, and genetic approaches to observe and manipulate pathogen specific T cell responses. They are currently dedicated to elucidating the developmental cues that govern T cell migration to different anatomical locations, commitment to the memory lineage, and the contribution of memory T cell differentiation state and location to protection from re-infection. Memory T cells that reside within the respiratory, intestinal, and reproductive mucosa, which collectively represent the most common portals of pathogen entry or infection, are of particular interest. By understanding these issues, they hope to contribute to the development of better vaccination strategies and therapies for chronic diseases. View publications here.
The major focus of the Mueller Lab is the investigation of the biological and biochemical mechanisms that underlie the maintenance of T-cell tolerance within the peripheral immune system. Investigations carried out by Dr. Daniel Mueller are leading to a better understanding of the biological and biochemical nature of immune self-tolerance. Of particular interest are those factors that determine whether prolonged and continuous antigen stimulation of a T-cell will lead to an increase in the clone size and the development of protective (or pathological) effector function, or lead to its functional inactivation (clonal anergy) and T-cell tolerance. Experiments are underway that investigate the repertoire of human autoreactive B cells in normals as well as in patients with Rheumatoid Arthritis and Systemic Lupus Erythematosus. View publications here.
The Peterson lab is focused on the molecular underpinnings of autoimmune diseases, including rheumatoid arthritis, lupus, and myositis. The laboratory utilizes genetic, biochemical, and primary human sample-based approaches to investigating the mechanisms whereby recently identified “risk” genes predispose to development of autoimmune disease. Dr. Peterson's group recently identified a role for Ptpn22, a potent “risk” gene for many autoimmune diseases, in the promotion of toll-like receptor signaling and type 1 interferon production. He is currently investigating the role of Ptpn22 in myeloid cell functions in systemic lupus and in responses to immunization, and is characterizing the molecular mechanism of Ptpn22 promotion of type 1 interferon signals. View publications here.
The Schwertfeger lab is interested in the mechanisms that drive macrophage-tumor cell interactions and the internal signaling in macrophages that causes them to respond the way they do in the tumor microenvironment. If signaling mechanisms can be identified, they could be targets for therapeutic intervention. Schwertfeger’s team is currently exploring three macrophage signaling molecules involved in normal macrophage functioning and that of other cell types. They include two transcriptions factors, STAT3 and STAT5, and the cell-surface enzyme ADAM17, which is involved in a spectrum of regulatory activities that includes cleaving of cell-surface-bound growth factors, freeing them to carrying out their cellular functions. Schwertfeger and her colleagues have found that activation of the fibroblast growth factor receptor (FGFR)-STAT3 pathway induces accumulation of the extracellular matrix carbohydrate hyaluronan, which promotes tumor proliferation and migration. Although drugs targeting STAT transcription factors or ADAM17 enzymes are plausible, how inhibiting these pathways would affect immune system function in healthy and tumor tissue is unknown and is a related research interest of Schwertfeger’s laboratory. Schwertfeger’s laboratory is also exploring how breast cancer cells interact with osteoclasts to promote bone metastasis using the FGFR signaling pathway. The research is trying determine whether the pathway is important in the ability of breast cancer cells to activate osteoclasts, initiate bone degradation and form osteolytic breast cancer lesions. The FGFR pathway can be targeted, with a number of inhibitors currently in clinical trials for treating primary tumors but not metastasis. Schwertfeger’s goal is to see whether the FGFR pathway inhibitors can be used to inhibit breast cancer metastasis.
Multiple immune tolerance mechanisms prevent self-reactive T cells from becoming pathogenic. Autoimmunity occurs when these mechanisms break down. Thymic selection, also referred to as central tolerance, is the first prevention a self-reactive T cell encounters. During this process antigen recognizing T cell receptors (TCRs) are tested against various self-peptides, those that react too strongly are either deleted or shuttled into the regulatory T cell lineage. My research aims to understand how self-reactive T cells escape this process and initiate autoimmune disease. One hypothesized method is through the expression of two different TCRs on a single T cells. We hypothesize that this dual TCR expression can limit deletion and regulatory T cell commitment of strongly self-reactive T cells in the thymus. Dual TCR expression is hypothesized to play important roles in several other immune contexts including allo-responses in graft rejection, allergy, and protective immunity. We have developed new tools in our lab that allow us to detect and study dual TCR T cells in several immune contexts. A second area of interest for the lab is neonatal immune development. At birth, the adaptive immune system is underdeveloped and may function differently than that of adults. As a result, infections are common in neonates and infants. The Schuldt Lab has begun a collaboration to investigate how early microbial exposure influences the development of adaptive immunity. Improved understanding of neonatal adaptive immunity could lead to improved vaccine platforms.
The Shimizu lab is working on research that is focused on role of integrins in T-cell adhesion and activation. The integrins are a superfamily of cell adhesion receptors that T-cells use to carry out many of their normal functions, including their ability to migrate to sites in the body where they are needed. The Shimizu lab has identified novel signaling intermediates that promote integrin function and T-cell activation, and are currently investigating the role of integrins in controlling the localization of T-cells to specific anatomic sites in the body. Of particular interest is the tumor microenvironment, which is normally immunosuppressive and thus dampens the ability of T-cells to recognize and kill tumor cells. Sophisticated imaging technologies such as two-photon microscopy now make it possible to track the movement and behavior of T-cells in the normal and tumor tissue microenvironments. Currently, Shimizu and colleagues are using this technology to analyze the behavior of cytotoxic T-cells in the tumor microenvironment and the role of integrins and immune checkpoint blockade in controlling T-cell movement and retention in the tumor microenvironment. View publications here.
The Stromnes laboratory is focused on advancing the understanding of cancer immunology and immunotherapy, with a particular emphasis on properties of the tumor and the tumor microenvironment that influence antigen-specific T lymphocyte migration and function. The laboratory aims to uncover how tumors and their mutations coordinate a suppressive microenvironment and elicit a program of T cell dysfunction. The lab is also focused on understanding the cellular and acellular components of tumor microenvironment that influence immunotherapy response. The laboratory combines studies of human tumors, genetically engineered mouse models that faithfully recapitulate human cancer, and novel cell engineering approaches evaluated in both mouse and human T cells to develop next generation cellular therapies for intractable malignancies, with a major focus on carcinomas including pancreatic cancer. Stromnes lab publications
The Vezys lab studies CD8 and CD4 T cell responses in autoimmunity and chronic infections. Specifically, the laboratory is examining how persistent interaction with cognate antigen impacts T cell selection, differentiation and survival. They observe and manipulate the dynamics of T cell responses specific for chronic viral infections or host derived self-proteins using MHC tetramers, adoptive transfer of transgenic T cells and fluorescence flow cytometry. They are currently interested in understanding what maintains the population of memory T cells specific for persistent pathogens, such as polyoma and lymphocytic choriomeningitis viruses. In addition, the lab is interested in elucidating how tolerance is induced and maintained to intestinal protein, as breakdown of this can lead to diseases such as ulcerative colitis and Crohn’s disease. By understanding these processes, we can learn how to manipulate the immune system for eradication of persistent infections, as well as interfering with the development and progression of autoimmunity. View publications here.
The Williams lab main focus is to determine the contributions of the myeloid cell compartment in the pathogenesis of metabolic and cardiovascular diseases, like atherosclerosis. By understanding cellular heterogeneity, localization, and molecular communication pathways, we can develop models to determine how monocytes and macrophages contribute to inflammation progression, as well as resolution. Using cutting edge approaches including single-cell transcriptomics, intravital imaging, and new animal models, we aim to push current boundaries in cardiovascular research into translatable findings by identifying targetable pathways to modify cardiovascular risk associated with chronic vascular inflammation.