Buckner Laboratory

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 cell function, and immunologic phenotyping of human lymphocytes. Their studies focus on Type 1 diabetes, rheumatoid arthritis, multiple sclerosis, systemic lupus and relapsing polychondritis.

Ongoing Studies:

1. De novo generation of CD4+CD25+Foxp3+ regulatory T cells
These studies focus on examining the mechanisms which lead to the de novo generation of TR from non-regulatory cells, the fate of these cells and the character of the antigens to which these newly generated TR are specific. Further studies are underway to determine whether the ability to generate self-reactive T cells is defective in patients with autoimmune disease, including T1D and SLE.

2. 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 TR 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 TR as a therapeutic approach for use in T1D, and donor specific TR as a therapeutic application in the setting of organ transplant.

3. Mechanisms of altered lymphocyte function in type 1 diabetes
These studies focus on the question of whether the lymphocytes of individuals with autoimmunity are refractor 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 begun to examine the intracellular mechanisms which result in altered T and B cell function in individuals with Ttype 1 diabetes.

4. 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. Initial studies have focused on the impact of the PTPN22 1858T variant on lymphocyte function. This work has now been expanded to examine how inhibition of the antigen receptor signaling pathways may impact T and B cell fate decisions and promote the development of autoimmunity.

5. Understanding the role of HLA susceptibility genes in the development of rheumatoid arthritis and the identification of novel T cell epitopes in rheumatoid arthritis.

6. Genetic and Immunologic contributions to relapsing polychondritis.

Relapsing Polychondritis Studies

Buckner Lab Members:

Jane Buckner, MD, Director, Translational Research Program

S. Alice Long, PhD- Research Scientist

I am interested in understanding activation parameters that influence FoxP3 expression and better defining the subset of cells capable of expressing Foxp3. By treating cells isolated form healthy control subjects and SLE patients with immunosuppressants and growth factors, I hope to map-out requirements for FoxP3 induction. This knowledge will be applied to isolate and expand regulatory T cells for adoptive cellular therapy.

Anya Schneider, MD- Postdoctoral Research Associate

As a German physician specializing in neurology, I find the field of autoimmunity extremely interesting and would like to develop more in-depth knowledge and skills. As a postdoctoral research fellow I focus my work on the function of regulatory T cells and if autoreactive T cells become refractory to downregulation. In this context the development of immunomodulatory therapies seems to be a worthwhile goal.

Megan Tatum - Research Technician

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 & Th2 cells, antigen specific Treg generation, and investigating the mechanism behind various genetic factors and disease.

Andrew Funk - Laboratory Aide