Jane Buckner, MD, Director, Translational Research Program, BRI Associate Director
Dr. Jane Buckner's laboratory is focused on understanding the regulation of the human immune response to self-antigens and the pathogenic mechanisms which result in autoimmunity. The expertise of her research group includes the study of human regulatory T cells, the identification of autoantigens that are the targets of autoimmunity in human disease and the role T cells specific for these autoantigens play in autoimmunity. In addition, the Buckner Lab has ongoing studies assessing the link between specific genetic variants associated with autoimmunity and their contribution to the pathologic mechanisms that result in autoimmunity.
The Buckner Lab has extensive experience with the use of MHC class II tetramers, T cell cloning, assays of T and B cell function, and immunologic phenotyping of human lymphocytes. The lab studies focus on Type 1 diabetes, rheumatoid arthritis, multiple sclerosis, systemic lupus and relapsing polychondritis.
1. Mechanisms of altered lymphocyte function in autoimmunity. These studies focus on the question of whether the lymphocytes of individuals with autoimmunity are refractory to normal regulatory signals. These studies specifically address the question of whether islet specific T cells from patients with Type 1 diabetes are refractory to normal regulation. More recently our group has extended this work to relapsing remitting multiple sclerosis.
2. Defining the role of altered cytokine signaling pathways on autoimmunity. Our group has demonstrated alterations in responses to cytokines including IL-2 and IL-6 in the setting of autoimmunity. We are now examining the mechanisms by which these signaling pathways are altered and the impact of these alterations on T cell fate and function.
3. Phenotype-Genotype Studies. These studies have been developed to identify the pathways that contribute to autoimmunity by taking advantage of recent discoveries in the genetics of autoimmunity. These include studies of the impact of the autoimmunity associated PTPN22 1858T variant and additional coding variants associated with T1D on T and B cell responses and an examination of SLE risk variants with the potential to alter B cell development and function.
4. In vitro induction, isolation and expansion of antigen specific CD4+CD25+Foxp3+ regulatory T cells. Our goal is to optimize conditions for the generation of tissue specific Treg and to establish protocols for their expansion in vitro with the purpose of extending this work to cell based therapy. Currently the laboratory is focused on the development of islet specific Treg as a therapeutic approach for use in T1D, and donor specific Treg as a therapeutic application in the setting of organ transplant.
5. The identification of novel T cell epitopes in rheumatoid arthritis. We have identified novel synovial T cell epitopes in RA, and develop HLA class II tetramers to detect autoreactive T cells. We are now using this as a tool to understand the pathogenesis of RA, to predict the development of RA in order to assist in the development of treatments to prevent the development of RA.
6. Genetic and Immunologic contributions to relapsing polychondritis.
Buckner Lab Members:
Tania Habib - Staff Scientist
My research is focused on understanding the immunologic and genetic causes of Type I diabetes and systemic lupus erythematosus. Through collaborative genotype-phenotype studies I am addressing the question of how genetic risk variants associated with these autoimmune diseases lead to functional changes during B cell maturation that contribute to altered immune responses and a loss of B cell tolerance. Translation of these studies to the disease setting will lead to an increased understanding of early disease mechanisms and assist in defining targets for therapeutic intervention.
Michael Turner – Staff Scientist
I am investigating how a genetic variation in the PTPN22 gene, which is associated with several autoimmune diseases, affects the development and function of T lymphocytes and leads to the accumulation of these pathogenic cells in individuals who carry this genetic risk factor and in patients who have developed an autoimmune disease.
Christian Hundhausen – Staff Scientist
I joined Jane Buckner’s lab as staff scientist in November 2012. I am interested in mechanisms of aberrant immune responses leading to chronic inflammation and autoimmune diseases. My current research focuses on genotype-phenotype studies on novel gene variants associated with Type 1 diabetes.
Shipra Gupta – Staff Scientist
My research in the Buckner Lab focuses on understanding regulatory T cells (Tregs) expanded for Treg cell therapy for treatment of Type 1 diabetes. I am also studying the role of inhibitory receptors on T cell subsets in multiple autoimmune diseases.
Hannes Uchtenhagen- Visiting Postdoctoral Fellow
I have just completed my PhD at the Karolinska Institutet in Stockholm working on the molecular details of MHC-I peptide presentation and TCR-recognition. With that background, I am now excited to turn my focus on human immunology and the role of MHC risk alleles in driving rheumatoid arthritis and multiple sclerosis. I am particularly interested in using the increasing knowledge of which T-cell targets are implicated with autoimmunity in order to study their potential deregulations at greater molecular depth.
Elizabeth Samuelson – Postdoctoral Fellow
I am studying the role of B cells in the development of autoimmune disease. I have an interest in B cell signaling and this contributes to variations in B cell development in SLE patients compared to healthy controls.
Anna Long – Postdoctoral Associate
I completed my PhD working on Type 1 diabetes at the University Of Bristol (UK) in 2013. My doctoral thesis was concerned with the rising incidence of diabetes and explored alterations in islet autoantibodies, genetics, and markers of hygiene associated with this. I will be working at BRI for two years before returning to the UK to complete my project exploring the regulation of the immune system in individuals who progress slowly to diabetes despite high risk of disease.
Megan Tatum - Research Technician
As a Research Technician I have worked closely with post cocs in the lab on a variety of different projects. Currently my research is focusing on T regulatory cells and their roll in various autoimmune diseases.
Mary Rieck - Research Technician
My role in the Buckner Lab focuses on training, organizing and coordinating essential operations within the laboratory, and taking on various pilot projects throughout the range of the lab's interests. My projects in the lab have included looking at differential responses between Th1 and Th2 cells, antigen specific Treg generation, and investigating the mechanism behind various genetic factors and disease.
Warren Anderson- Research Technician
I perform various experiments pertaining to cell culturing and isolations. I also assist in research and analysis of various immunological studies being performed in the Buckner Lab.
Tuan Nguyen – Laboratory Aide
I have learned a great deal in my 15+ years of working at BRI, techniques ranging from isolation of PBMC to typing of genes for ongoing projects around the lab. I assist with lab experiments, in any way needed.
Andrew Funk - Laboratory Aide
I work in the Buckner Lab focusing on the effect of genetic variants in B cell and T cell receptor signaling. Through this work we hope to achieve a greater understanding of diseases such as Type 1 diabetes and lupus.
Angel Paullin –Laboratory Aide
My role as lab aide is to help serve as a backbone to the entirety of the lab. My supporting role allows me to work to keep the research in the lab running smoothly, quickly, and most efficiently.