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Jesica James

2017 Gina M. Finzi Memorial Student Fellow

Project Summary:

Systemic Lupus Erythematosus (SLE) is a painful connective tissue disorder that affects women 9 times out of 10. This distinct gender bias cannot be fully explained by hormonal differences between the sexes, and in the past decade there has been increasing evidence that sex chromosomes play a role in SLE development.

Female mammals with two X chromosomes undergo a process known as X chromosome inactivation (XCI) to silence gene expression from one X chromosome early in embryonic development. This process is critical to keeping expression of X chromosome genes similar to men, who only have one X chromosome.

Some X chromosome genes escape inactivation or escape variably between individuals, resulting in higher expression than normal. Comparisons between men and women affected or unaffected by SLE have suggested that gene escape may play a role in SLE susceptibility, but no studies have assessed whether immunity related genes escape XCI in SLE patients.

We believe that silencing may be improper in SLE-affected women, particularly in genes necessary for immune system function, driving both susceptibility to disease and the SLE gender bias. To test our hypothesis, we propose to assess inactive X chromosome expression of three SLE candidate genes in multiple cell types taken from SLE patients.

Successful identification of inactive X expression for these genes would take us one step further in understanding how women develop SLE and would uncover new pathways researchers could use to further develop novel therapies.