Multiple Sclerosis (MS) and Type 1 diabetes (T1D) are organ-specific disorders that are the result of an attack of the immune system against the body's own central nervous system (CNS) and insulin-producing beta cells in the pancreas, respectively (see selected publication #6). Pro-inflammatory CD4+ T lymphocytes that are reactive to proteins of the CNS or the pancreas have been identified as main mediators of these autoimmune diseases. Although most healthy individuals harbor such self-reactive T cells, few will ever develop MS or T1D. We investigate the cellular and molecular mechanisms that are responsible for maintaining or breaking this resistance to the development of autoimmunity in mouse models of MS (see selected publications #1-3) or T1D (see selected publication #4). Another focus of the laboratory involves the identification of small molecule compounds that regulate pro-inflammatory T cell responses (see selected publications #5, 7). We use these compounds as tools to gain new insights into molecular mechanisms of autoimmunity and as leads for the development of potential novel therapeutics for MS or T1D.

Selected publications:

1. Fulminant spontaneous autoimmunity of the central nervous system in mice transgenic for the myelin proteolipid protein-specific T cell receptor.
Waldner H, Whitters MJ, Sobel RA, Collins M, Kuchroo VK.
Proc Natl Acad Sci U S A. 2000 Mar 28;97(7):3412-7. PMID:15735651

2. Activation of antigen-presenting cells by microbial products breaks self tolerance and induces autoimmune disease.
Waldner H, Collins M, Kuchroo VK.
J Clin Invest. 2004 Apr;113(7):990-7. PMID: 15057305

3. Epitope spreading initiates in the CNS in two mouse models of multiple sclerosis.
McMahon EJ, Bailey SL, Castenada CV, Waldner H, Miller SD.
Nat Med. 2005 Mar;11(3):335-9. Epub 2005 Feb 27. PMID: 15735651

4. The autoimmune diabetes locus Idd9 regulates development of type 1 diabetes by affecting the homing of islet-specific T cells.
Waldner H, Sobel RA, Price N, Kuchroo VK.
J Immunol. 2006 May 1;176(9):5455-62. PMID:16622013

5. Identifying druglike inhibitors of myelin-reactive T cells by phenotypic high-throughput screening of a small-molecule library.
Rossi C, Padmanaban D, Ni J, Yeh LA, Glicksman MA, Waldner H.
J Biomol Screen. 2007 Jun;12(4):481-9. Epub 2007 May 3. PMID:17478482

6. The role of innate immune responses in autoimmune disease development.
Waldner H.
Autoimmun Rev. 2009 Mar;8(5):400-4. Epub 2009 Jan 20. PMID: 19162250

7. Halofuginone inhibits TH17 cell differentiation by activating the amino acid starvation response.
Sundrud MS, Koralov SB, Feuerer M, Calado DP, Kozhaya AE, Rhule-Smith A, Lefebvre RE, Unutmaz D, Mazitschek R, Waldner H, Whitman M, Keller T, Rao A.
Science. 2009 Jun 5;324(5932):1334-8. PMID: 19498172