My name is Ami Yamamoto, and I have the great opportunity of being one of the Lupus Foundation of Minnesota’s Student Summer Fellows for 2013. This summer, I am studying under Erik Peterson, M.D., in the Department of Rheumatic and Autoimmune Diseases at the University of Minnesota–Twin Cities.
As I will write about in more detail in a later post, my project is to contribute to research on the gene PTPN22 which Dr. Peterson and his team thinks to be a “risk” gene for Systemic Lupus Erythematosus (SLE). The first step for the project is gathering approximately 150 SLE patient participants and genotyping their DNA (extracted from a small tube of blood they donated for the cause) to determine whether they have the “LypR” variant or the “LypW” variant. We hypothesize that patients with the “LypW” variant (who we call “carriers”) are at higher risk for SLE and that SLE patients with LypW variant PTPN22 have a different immune response than other SLE patients. If our hypothesis is proven correct, this would mean that SLE patients with LypW PTPN22 would need to be treated differently than other patients.
Once we have genotyped some subjects, we call back age and sex-matched carriers and non-carriers to donate some more blood for the research project. We also have to be careful that patients are not currently taking drugs that would alter immune response so that we get a better comparison between the immune response of carriers and non-carriers. We will run a variety of tests (using flow cytometry and gene expression assays) to look at type 1 IFN gene expression signatures (associated with PTPN22) and to compare Toll-like Receptors 4, 7, and 9 signaling between carriers and non-carriers. Finally, we will correlate type 1 IFN gene expression signatures with TLR signaling phenotypes between LypW variant allele carriers versus non-carriers in SLE patients.
In the current general SLE model, SLE patients are associated with elevated type 1 IFN. However, if our hypothesis is correct, the results would indicate reduced type 1 IFN in LypW carrier SLE patients. This would give rise to a valuable new model where LypW carrier SLE patients should be considered as type 1 IFN deficient and hence would require contrasting treatment methods in comparison to current general SLE patients.
I am so thrilled to be a part of such an interesting and important clinical and translational research project!