CADRe Research and Our Team
A singular focus leads to success
We believe there's real power in focusing on the universal characteristics of rheumatic and autoimmune diseases. And today, we're harnessing the power of big data and personalized medicine to make an impact.
For example, we're at the forefront of using large data sets to pinpoint the most promising molecules for investigation. We now have tools to explore the enormous troves of disease data in new ways. Instead of pursuing a project based on a preconceived notion about what molecules might be important to disease, we can use powerful statistical programs to look at all molecules. Based on the patterns such programs uncover, we can find promising avenues that might have taken us years—even decades—to discover in the past.
Already, we have found success using this approach. For example, our researchers have identified a molecule, interferon alpha, which is a marker for specific autoimmune diseases such as lupus. Promising trials are currently underway that will neutralize this harmful molecule in patients. This discovery has opened up the field for dozens of other researchers to pursue related work as well.
At CADRe, we're proud to have some of the top researchers in the autoimmunity and rheumatology fields as part of our team of researchers. We are excited by the work they're doing to advance research in the fields of Rheumatoid Arthritis, Lupus, Type 1 Diabetes, and more, and we'd like to share their enthusiasm and passion for finding a cure for autoimmune diseases with you.
Bryce Binstadt, MD, PhD
Associate Professor, Pediatrics
Research Areas: Autoimmune diseases, Arthritis, Cardiovascular inflammation, Diabetes
The Binstadt laboratory studies the immune mechanisms that cause autoimmune and inflammatory diseases. Ongoing projects in the lab include understanding a) the contributions of macrophages to cardiovascular inflammation and fibrosis in the context of systemic rheumatic diseases, b) how dual T cell receptor (TCR) T cells contribute to normal immune system function and to autoimmune disease pathogenesis, and c) neurologic control of inflammatory arthritis. All of these projects are in mouse models, but each has potential for translation to human studies. For instance, we have defined a key role for dual TCR T cells in a mouse model of autoimmune diabetes; we are now poised to study this cell type in patients with type I diabetes.
Parastoo Fazeli, MD
Assistant Professor, Rheumatic and Autoimmune Diseases
Research Areas: Lupus, Lupus in Pregnancy
Dr. Fazeli's main interest lies in research on new biological drugs to manage lupus for patients who do not respond to current therapies or cannot tolerate them. Dr. Fazeli looks to find new treatments and new drugs not only to control lupus but also to allow women who suffer from infertility due to lupus or side effects of lupus treatments, to experience pregnancy and have healthy children.
Tanya Freedman, PhD
Assistant Professor, Pharmacology
Research Areas: Macrophage signaling, Src-family kinase regulation, Autoimmune Disease
Current therapies for macrophage-associated autoimmune diseases such as rheumatoid arthritis (RA) and juvenile idiopathic arthritis (JIA) suppress normal immune function. I have shown that the Src-family tyrosine kinase LynA is uniquely required for hypersensitive macrophage signaling in the presence of inflammation (as in inflamed joints), but is not required for pathogen-induced signaling. This predicts that inhibition of LynA signaling could relieve symptoms of autoimmune disease without suppressing innate immune function. We are currently testing the role of LynA signaling in macrophage hypersensitivity and evaluating the translational applications of our basic signaling discovery. This work could ultimately lead to a better mechanistic understanding of human inflammatory disease and safer therapeutic approaches to treating RA, JIA, and other autoimmune diseases.
Kristin Hogquist, PhD
Professor, Laboratory Medicine and Pathology
Research Areas: Molecular mechanisms of T cells in the thymus, Gene expression profiling, Autoimmune response to Epstein Barr Virus
My research goals are to understand how the thymus acts to generate functional and safe T cells. Specifically, my group is examining the mechanisms of positive and negative selection, Treg induction, and development of intraepithelial lymphocytes and lipid specific T cells in the thymus. We primarily use animal models (mice) and study thymic function in the healthy steady state. Our research helps establish the principals by which we understand tolerance dysfunction during disease. It is my hope that participation in CADRe will inspire and shape our research in humans, and in more disease relevant mouse models.
Stephen Jameson, PhD
Professor in Experiment Pathology, Laboratory Medicine and Pathology
Research areas: CD8+ T cell tolerance; effect of microbial infections on autoimmuity
Daniel Mueller, MD
Professor, Rheumatic and Autoimmune Diseases
Research areas: Rheumatoid Arthritis, Immunology
My research program examines the regulation of CD4 T cell and B cell antigen responsiveness in individuals prone to the development of autoimmune arthritis. In particular, we are investigating the relationship between Foxp3+ T regulatory cells and the control of CD4 T cell clonal anergy induction in the normal protection against the breakdown of polyclonal B cell tolerance and development of autoimmune arthritis. To date, the majority of our work has been in mice. Nonetheless, advances in B cell antigenic tetramer technology have allowed us to investigate autoreactive blood B cells in rheumatoid arthritis (RA) patients. We have recently discovered expanded clades of highly mutated citrullinated-alpha enolase or -filiggrin reactive B cells in the blood of RA patients. We are now examining the relationship between immunoglobulin gene hypermutation, clonal expansion, and the B cell transcriptome, and will soon compare the affinity of these human B cell's antibodies to their pathogenicity in mice.
In addition to supporting essential technologies and services for my translational research (e.g., IRB support, RA cohort development, sample collection and processing, antigen tetramer production), it is my hope that collaborations arising from this CADRe involvement will enhance my research success.
Erik Peterson, MD
Associate Professor, Rheumatic and Autoimmune Diseases
Research Areas: Autoimmune diseases, Genetics, Lupus, Rheumatoid Arthritis
Dr. Peterson has a long-standing interest in the mechanisms by which genes promote autoimmune disease. In 2004, geneticists identified leukocyte-specific gene PTPN22 as a driver of susceptibility to rheumatoid arthritis and other major human autoimmune syndromes. Dr. Peterson's group identified a role for PTPN22 in the toll-like receptor engaged signaling pathway leading to upregulation of type 1 interferon. Further, his lab discovered that the gene works through the innate immune cells that produce interferons to suppress joint disease in a mouse model of rheumatoid arthritis. More recent work has focused on the function of Natural Killer cells, lymphocytes that can modulate immunity and suppress inflammation. Dr. Peterson has found evidence that PTPN22 can promote signaling in NK cells that leads to upregulation of the cytokine Interferon-gamma, which has been shown to suppress inflammatory arthritis. Dr. Peterson's group is now mounting studies of NK cells from human autoimmune disease patients to determine whether the rheumatoid arthritis-associated variant of PTPN22 exerts differential effects on NK production of interferon gamma.
Anna Shmagel, MD
Assistant Professor, Rheumatic and Autoimmune Diseases
Research areas: Arthritis, Chronic Inflammation, Gastroenterology
I am interested in learning how the environment (and diet specifically) influences the risk of developing arthritis and chronic inflammation. Using quantitative methods, I would like to better understand the connections between dietary factors, gut bacteria, and the systemic inflammatory response.