Anura Hewagama

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Marta E. Alarcón-Riquelme20
Amr H. Sawalha16
Bruce C. Richardson14
John B. Harley11
Kenneth M. Kaufman11
13Bruce C. Richardson
8Faith M. Strickland
7B C Richardson
7Dipak R Patel
6Ian R. Mackay

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2013
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The genetics and epigenetics of autoimmune diseases.
Self tolerance loss is fundamental to autoimmunity. While understanding of immune regulation is expanding rapidly, the mechanisms causing loss of tolerance in most autoimmune diseases remain elusive. Autoimmunity is believed to develop when genetically predisposed individuals encounter environmental agents that trigger the disease. Recent advances in the… (More)
Stronger inflammatory/cytotoxic T cell response in women identified by microarray analysis
Women develop chronic inflammatory autoimmune diseases more often than men. The mechanisms causing the increased susceptibility are incompletely understood. Chronic immune stimulation characterizes many autoimmune disorders. We hypothesized that repeated stimulation may cause a different T-cell response in women than in men. Microarrays were used to compare… (More)
Stimulatory and inhibitory killer Ig-like receptor molecules are expressed and functional on lupus T cells.
T cells from lupus patients have hypomethylated DNA and overexpress genes normally suppressed by DNA methylation that contribute to disease pathogenesis. We found that stimulatory and inhibitory killer cell Ig-like receptor (KIR) genes are aberrantly overexpressed on experimentally demethylated T cells. We therefore asked if lupus T cells also overexpress… (More)
Overexpression of X-linked genes in T cells from women with lupus.
Women develop lupus more frequently than men and the reason remains incompletely understood. Evidence that men with Klinefelter's Syndrome (XXY) develop lupus at approximately the same rate as women suggests that a second X chromosome contributes. However, since the second X is normally inactivated, how it predisposes to lupus is unclear. DNA methylation… (More)
Anchoring a cationic ligand: the structure of the Fab fragment of the anti-morphine antibody 9B1 and its complex with morphine.
The crystal structures of an anti-morphine antibody 9B1 (to 1.6A resolution) and its complex with morphine (to 2.0 A resolution) are reported. The morphine-binding site is described as a shallow depression on the protein surface, an unusual topology for a high-affinity ( Ka approximately 10(9) M(-1)) antibody against a small antigen. The polar part of the… (More)
Environmental exposure, estrogen and two X chromosomes are required for disease development in an epigenetic model of lupus.
Systemic lupus erythematosus (SLE) is an autoimmune disease primarily afflicting women. The reason for the gender bias is unclear, but genetic susceptibility, estrogen and environmental agents appear to play significant roles in SLE pathogenesis. Environmental agents can contribute to lupus susceptibility through epigenetic mechanisms. We used… (More)
Diet influences expression of autoimmune-associated genes and disease severity by epigenetic mechanisms in a transgenic mouse model of lupus.
OBJECTIVE Lupus flares occur when genetically predisposed individuals encounter appropriate environmental agents. Current evidence indicates that the environment contributes by inhibiting T cell DNA methylation, causing overexpression of normally silenced genes. DNA methylation depends on both dietary transmethylation micronutrients and ERK-regulated DNA… (More)
Diversity in hapten recognition: structural study of an anti-cocaine antibody M82G2.
Antibodies against cocaine and other drugs of abuse are the basis for diagnostic tests for the presence of those drugs in human serum. The 1.7A resolution crystal structure of the anti-cocaine monoclonal antibody M82G2 in complex with cocaine is presented. This structure determination was undertaken to establish the stereochemical features in the antibody… (More)
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