James Lord, MD, PhD
Research Assistant Member
James Lord received his PhD in Immunology through the University of Washington, Fred Hutchinson Cancer Research Center and Benaroya Research Institute at Virginia Mason (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 recently joined Virginia Mason Medical Center and has established his clinical practice at the Digestive Disease Institute, specializing in the care of patients with IBD.
Areas 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. In 2011, IBD was added to BRI’s biorepository program to archive research materials from the blood and colonoscopic biopsies of IBD patients. 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 known 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.
1. 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.
2. 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.
3. 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.
4. 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.
5. 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.
6. 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.
7. 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.
8. 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.
9. 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.
10. 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.
11. 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.
12. 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.
13. 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.
14. Lord, J.D., Vaillant-Saunders, K., Hahn, H., Thirlby, R.C., Ziegler, S.F. (2012) Paradoxically Increased FOXP3+ T Cells in IBD Do Not Preferentially Express the Isoform of FOXP3 Lacking Exon 2. Dig. Dis. Sci., submitted.
15. Lord, J.D., Chen, J., Kozarek, R.A. (2012) A Case of Fatal Idiopathic Enteritis and Multiple Opportunistic Infections Associated with Dendritic Cell Deficiencies. Gut, submitted.