James Lord, MD, PhD
Background Information
James Lord received his PhD in Immunology through the University of Washington, Fred Hutchinson Cancer Research Center and Benaroya Research Institute (BRI). He subsequently completed his MD at the University of Washington, where he remained for his internal medicine residency and clinical research fellowship in gastroenterology. During his fellowship, he returned to BRI to pursue a research project in the lab of Steven Ziegler, PhD, exploring the role of FOXP3+ regulatory T cells (Tregs) in the pathogenesis of human inflammatory bowel disease (IBD). He joined Virginia Mason Medical Center (VMMC) in 2010 and has established his clinical practice at the Digestive Disease Institute, specializing in the care of patients with IBD.
Area of Research
Dr. Lord continues to explore Tregs and other cells of the mucosal immune system in patients with IBD. Through a collaboration with Virginia Mason surgeon Richard Thirlby, MD, he has compiled an extensive archive of research materials and data from the surgically resected intestines of patients with and without IBD since 2006. In 2011, IBD was added to BRI’s biorepository program to archive research materials from the blood and colonoscopic biopsies of IBD patients seen in the VMMC Gastroenterology Division. Using these materials, he is now actively comparing the characteristics of circulating and mucosal immune cells in terms of their composition, expression of immunoregulatory molecules and cytokine signal transduction capabilities, and correlating his findings with clinical characteristics and genetic risk factors for IBD. This work is complemented by investigation of how other mucosal immune cells, such as dendritic cells, may influence the inhibitory potential of Tregs in functional assays.
Featured Publications
Nelson, B.H., Lord, J.D., and Greenberg, P.D. (1994) Cytoplasmic domains of the interleukin-2 receptor beta and gamma chains mediate the signal for T-cell proliferation. Nature. 369(6478):333-6. PMID 7514277.
Nelson, B.H., Lord, J.D., and Greenberg, P.D. (1996) A membrane-proximal region of the interleukin-2 receptor gamma c chain sufficient for Jak kinase activation and induction of proliferation in T cells. Mol Cell Biol. 16(1):309-17. PMID 8524310.
Lord, J.D., McIntosh, B.C., Greenberg, P.D., and Nelson, B.H. (1998) The IL-2 receptor promotes proliferation, bcl-2 and bcl-x induction, but not cell viability through the adapter molecule Shc. J Immunol. 161(9):4627-33. PMID 9794391.
Hunt, A.E., Lali, F.V., Lord, J.D., Nelson, B.H., Miyazaki, T., Tracey, K.J., and Foxwell, B.M. (1999) Role of interleukin (IL)-2 receptor beta-chain subdomains and Shc in p38 mitogen-activated protein (MAP) kinase and p54 MAP kinase (stress-activated protein Kinase/c-Jun N-terminal kinase) activation. IL-2-driven proliferation is independent of p38 and p54 MAP kinase activation. J Biol Chem. 274(11):7591-7. PMID 10066828.
Lord, J.D., McIntosh, B.C., Greenberg, P.D., and Nelson, B.H. (2000) The IL-2 receptor promotes lymphocyte proliferation and induction of the c-myc, bcl-2, and bcl-x genes through the trans-activation domain of Stat5. J Immunol. 164(5):2533-41. PMID 10679091.
Gu, H., Maeda, H., Moon, J.J., Lord, J.D., Yoakim, M., Nelson, B.H., and Neel, B.G. (2000) New role for Shc in activation of the phosphatidylinositol 3-kinase/Akt pathway. Mol Cell Biol. 20(19):7109-20. PMID 10982827.
Martino, A., Holmes, J.H. 4th, Lord, J.D., Moon, J.J., and Nelson, B.H. (2001) Stat5 and Sp1 regulate transcription of the cyclin D2 gene in response to IL-2. J Immunol. 166(3):1723-9. PMID 11160217.
Bollyky, P.L., Lord, J.D., Masewicz, S.A., Evanko, S.P., Buckner, J.H., Wight, T.N., and Nepom, G.T. (2007) Cutting Edge: High Molecular Weight Hyaluronan Promotes the Suppressive Effects of CD4+CD25+ Regulatory T Cells. J Immunol. 2007 Jul 15;179(2):744-7. PMID 17617562.
Alexander, J., Lord, J., Yeh, M., Cuevas, C., Bakthavatsalam, R., and Kowdley, K. (2008) Risk Factors for Recurrence of Primary Sclerosing Cholangitis after Liver Transplantation. Liver Transplantation. 14(2):245-51. PMID 18236405.
Lord J.D., Hackman R.C., Moklebust A., Thompson J.A., Higano C.S., Chielens D., Steinbach G., and McDonald G.B. (2010) Refractory Colitis Following Anti-CTLA4 Antibody Therapy: Analysis of Mucosal FOXP3(+) T Cells. Dig Dis Sci. 55(5):1396-1405. PMID 19507029.
Lord J.D., Hackman R.C., Wood, B., Moklebust A., Hockenbery, D. M., Steinbach G., Ziegler, S. F., and McDonald G.B. (2010) Blood and Gastric FOXP3+ T Cells Are Not Decreased in Human Gastrointestinal Graft Versus Host Disease. Biol Blood Marrow Transplant, 17(4):486-96. PMID 20870026.
Lord, J.D., Upton, M.P., Hwang, J.H. (2010) Confocal Endomicroscopic Evaluation of Colorectal Squamous Metaplasia and Dysplasia in Ulcerative Colitis. Gastrointestinal Endoscopy, 73(5):1064-6. PMID 21067733.
Bollyky, P.L., Wu, R.P. Falk, B.A., Lord, J.D., Long, S.A., Preisinger, A., Teng, B., Holt, G.E., Standifer, N.E., Braun, K.R., Xie, C., Samuels, P.L., Vernon, R.B., Gebe, J.A., Wight, T.N., Nepom, G.T., (2011) Extracellular matrix components guide TR1 regulatory T-cell induction from effector memory T-cell precursors. Proc Natl Acad Sci U S A. 108(19):7938-43. PMID 21518860.
Lord, J.D., Vaillant-Saunders, K., Hahn, H., Thirlby, R.C., Ziegler, S.F. (2011) Paradoxically Increased FOXP3+ T Cells in IBD Do Not Preferentially Express the Isoform of FOXP3 Lacking Exon 2. Dig. Dis. Sci., 57(11):2846-55. PMID 22736020.
McElrath M, Smythe K, Randolph-Habecker J, Melton K, Goodpaster T, Hughes S, Mack M, Sato A, Diaz G, Steinbach G, Novak R, Curlin M, Lord J, Maenza J, Duerr A, Frahm N, Hladik F; the NIAID HIV Vaccine Trials Network. (2013) Comprehensive assessment of HIV target cells in the distal human gut suggests increasing HIV susceptibility toward the anus. J Acquir Immune Defic Syndr. 63(3):263-71. PMID 23392465.
Lord, J.D., Chen, J., Kozarek, R.A. (2013) A Case of Fatal Idiopathic Enteritis and Multiple Opportunistic Infections Associated with Dendritic Cell Deficiencies. J Gastrointestin Liver Dis. 22(1):87-91. PMID 23539396.
Kurmaeva E, Lord JD, Zhang S, Bao JR, Kevil CG, Grisham MB, Ostanin DV. (2014) T cell-associated α4β7 but not α4β1 integrin is required for the induction and perpetuation of chronic colitis. Mucosal Immunol. 7(6): 1354-65. PMID 24717354.
Lord JD, Chen J, Thirlby RC, Sherwood AM, Carlson CS. (2014) T Cell Receptor Sequencing Reveals Diversity and Overlap of Colonic Effector and FOXP3+ T Cells in Ulcerative Colitis. Inflammatory Bowel Disease. 21(1):19-30. PMID 25795566.
Holgersen K., Kutlu B., Fox B., Serikawa B., Lord J.D., Hansen A.K., Holm T.L. (2015) High-resolution gene expression profiling using RNA sequencing in patients with inflammatory bowel disease and in mouse models of colitis. J. Crohns Colitis. 9(6):492-506. PMID 25795566.
Lord JD, Shows DM, Chen J, Thirlby RC. (2015) Human Blood and Mucosal Regulatory T Cells Express Activation Markers and Inhibitory Receptors in Inflammatory Bowel Disease. PLoS One. 10(8): e0136485. PMID 26305224.
Lord JD. (2015) Promises and paradoxes of regulatory T cells in inflammatory bowel disease. World J. Gastroenterology. 21(40): 11236-45. PMID 26523099.
Lord JD, Shows DM. (2017) Thiopurine Use is Associated with Reduced B and Natural Killer Cells in IBD. World J. Gastroenterology. [in press].
Boden EK, Shows DM, Chiorean MV, Lord JD. (2017) Integrin α4β7 Expression Preceding and Saturation During Vedolizumab Therapy Correlates with Treatment Response in Inflammatory Bowel Disease. [in press].
Lord JD, Long SA, Shows DM, Thorpe J, Schwedhelm K, Buckner JH. (2017) Circulating Integrin Alpha4/Beta7+ Lymphocytes Targeted by Vedolizumab Have a Pro-Inflammatory Phenotype. [manuscript in preparation].