My research focuses on understanding the etiology and pathogenesis of systemic autoimmune diseases. This requires unraveling vast networks of interconnected immune responses, a task that exceeds the limitations of traditional laboratory methods. My group applies high-throughput/high-content, precision medicine approaches to this problem. Our primary focus is defining, at a systems level, the pathways that influence the regulation and development of autoimmune responses.
I was involved in some of the early candidate gene association studies, and then in the whole genome association studies in lupus. I have also been intimately involved with large consortium studies and many follow-up fine mapping studies through my management of several large collections of lupus samples and data in the OMRF Biorepository and Sample Procurement Core. These results led to studies on the functional effects of disease-associated genetic variants, particularly in genes affecting the complement regulatory proteins/receptors, innate immune responses, and B cell signaling pathways.
To gain a high-level view of immune function in patients with autoimmune disease, we use a systems biology approach to combine data from our genetic/genomic studies, innovative biomarker assessments, cellular immunophenotyping experiments, and single cell proteomics analyses. Because multiple immune pathways can lead to the same autoimmune disease diagnosis, we also use these multidimensional datasets and associated clinical data to cluster patient subpopulations and model altered pathways in various populations. We apply these methods both in translational studies of cross-sectional and longitudinal autoimmune disease cohorts, and in investigator-initiated clinical trials. The ultimate goal of this work is to enable more accurate diagnosis, risk assessment before clinical disease onset, and prediction of therapeutic responses in order to improve patient care.
B.S., University of Iowa, Iowa City, IA, 1985
Ph.D., University of Kentucky, Lexington, KY, 1992
Postdoc, University of Colorado Health Sciences Center, Denver, CO, 1996
MSCIS, Regis University, Denver, CO
Joined OMRF Scientific Staff in 2002
Ward JM, Ratliff ML, Dozmorov MG, Wiley G, Guthridge JM, Gaffney PM, James JA, Webb CF. 2016. Human effector B lymphocytes express ARID3a and secrete interferon alpha. J Autoimmun. 75:130-140.
Dozmorov MG, Dominguez N, Bean K, Macwana SR, Roberts V, Glass E, James JA, Guthridge JM. 2015. B-cell and monocyte contribution to systemic lupus erythematosus identified by cell-type-specific differential expression analysis in RNA-seq data. Bioinform Biol Insights. 9(Suppl 3):11-19. PMCID: PMC4599594
Munroe ME, Vista ES, Guthridge JM, Thompson LF, Merrill JT, James JA. 2014. Proinflammatory adaptive cytokine and shed tumor necrosis factor receptor levels are elevated preceding systemic lupus erythematosus disease flare. Arthritis Rheumatol. 66(7):1888-99. PMCID: PMC4128244
Lu R, Munroe ME, Guthridge JM, Bean KM, Fife DA, Chen H, Slight-Webb SR, Keith MP, Harley JB, James JA. Dysregulation of innate and adaptive serum mediators precedes systemic lupus erythematosus classification and improves prognostic accuracy of autoantibodies. J Autoimmun. Nove;74:182-193. PMCID: PMC5079766
Slight-Webb S, Lu R, Ritterhouse LL, Munroe ME, Maecker HT, Fathman CG, Utz PJ, Merrill JT, Guthridge JM, James JA. 2016. Autoantibody-Positive Healthy Individuals Display Unique Immune Profiles That May Regulate Autoimmunity. Arthritis Rheumatol. Oct;68(10):2492-502. PMCID: PMC5042816
Dozmorov I, Dominguez N, Sestak AL, Robertson JM, Harley JB, James JA, Guthridge JM. 2013. Evidence of dynamically dysregulated gene expression pathways in hyperresponsive B cells from African American lupus patients. PLoS One. 8(8):e71397. PMCID: PMC3744560
Guo L, Deshmukh H, Lu R, Vidal GS, Kelly JA… and Guthridge JM. 2009. Replication of the BANK1 genetic association with systemic lupus erythematosus in a European-derived population. Genes Immun 10(5):531-8. PMCID:PMC2736873
The International Consortium for Systemic Lupus Erythematosus Genetics (SLEGEN) , Harley JB, Alarcón-Riquelme ME, Criswell LA, Jacob CO… Guthridge JM, et al. 2008. Genome-wide association scan in women with systemic lupus erythematosus identifies risk variants in ITGAM, PXK KIAA1542 and other loci. Nat Genet. 40(2):204-10. PMCID: PMC3712260
Nath SK, Han S, Kim-Howard X, Kelly JA, Viswanathan P… Guthridge JM*, and Harley JB*. A nonsynonymous functional variant in integrin-alpha(M) (encoded by ITGAM) is associated with systemic lupus erythematosus. Nat Genet. 2008;40(2):152-4. (*authors contributed equally)
Arthritis & Clinical Immunology Research Program, MS 53
Oklahoma Medical Research Foundation
825 N.E. 13th Street
Oklahoma City, OK 73104
Phone: (405) 271-2600
Fax: (405) 271-7063