Human genetics in rheumatoid arthritis guides of high-throughput drug screen of the CD40 signaling pathway, Li G, Diogo D, Wu D, Spoonamore J, Dancik V, Franke F, Kurreeman F, Rossin EJ, Duclos G, Hartland C, Zhou X, Li K, Liu J, De Jager PL, Siminovitch KA, Zhernakova A, Raychaudhuri S, Bowes J, Eyre S, Padyukov L, Gregersen PK, Worthington J, Rheumatoid Arthritis Consortium International (RACI), Gupta N, Clemons PA, Stahl E, Tolliday N, Plenge RM. PLoS Genetics. 2013 May, in progress.
We demonstrate how to leverage human genetics for drug discovery. Genetics of risk of RA points to a pathway (CD40-CD40L signaling) and a HTS assay (NF-kB luciferase-reporter in a B cell line), which was used in a pilot small molecule drug screen at the Broad Institute.
PhIP-seq characterization of autoantibodies from patients with multiple sclerosis, type 1 diabetes and rheumatoid arthritis, Larman HB, Laserson U, Querol L, Verhaeghen K, Solimini NL, Xu GJ, Klarenbeek PL, Church GM, Hafler DA, Plenge RM, Nigrovic PA, De Jager PL, Weets I, Martens GA, O’Connor KC, Elledge SJ. J Autoimmun. 2013 Mar 13. [Epub ahead of print] PMID: 23497938
In collaboration with the Elledge lab, we performed a genome-wide search for autoantigens in patients with autoimmune disease.
A Novel Polymorphism of the Human CD40 Receptor with Enhanced Function. Peters AL, Plenge RM, Graham RR, Altshuler DM, Moser KL, Gaffney PM, and Bishop GA. Blood 2008 Sep 1;112(5):1863-71. PMID: 18591382
We examined the functional consequences of a CD40 polymorphism present at high-frequency among individuals of Native American ancestry.View article PDF