Professor of Medicine Bruce Richardson, M.D., Ph.D., is a Rheumatologist with a research interest in the mechanisms causing human systemic lupus erythematosus. Lupus is an autoimmune disease that primarily affects women, and is caused by agents in the environment that trigger the disease in genetically predisposed people. The environmental agents inhibit DNA methylation, a repressive epigenetic mechanism, in lymphocytes. DNA methylation silences genes that are inappropriate or detrimental to the function of any given cell, and inhibiting DNA methylation activates their expression. We found that inhibiting DNA methylation converts normal, antigen specific "helper" T lymphocytes into autoreactive, inflammatory, cytotoxic cells that cause the disease.

"The DNA Sequencing Core has been essential to the success of our studies in many ways," Professor Richardson explained. "Their state of the art technology allowed us to identify and map the DNA sequences that demethylate in T cells, confirming that their aberrant expression is due to DNA demethylation. We have done this using in vitro models, mouse models, and lymphocytes from women with lupus, all with the help of the DNA Sequencing Core."

Their most recent studies demonstrate that women are primarily affected by lupus because they have 2 X chromosomes, while men have an X and a Y, and the second X chromosome is normally silenced by DNA methylation. The second X demethylates in women lupus, causing overexpression of genes that contribute to the disease (men can't do this).

"These studies would have been impossible without the DNA core. The cost of the equipment and the expertise to run it is beyond what normal research grants (NIH, foundations, VA) can support," he said. "The equipment is also continually updated, permitting cutting edge work. I have found that when I write grants and need to explain to the reviewers how I will do the studies, all I need to say is that they will be done in the University of Michigan DNA Sequencing Core and provide them the link to their website. This always works. Finally, over the years I have been invited to take positions at other institutions. I have turned them down because they lack similar, institutionally supported core facilities."