105D Whitehead Bldg., 615 Michael Street
Atlanta, GA 30322
404 727-8547 Phone
Assistant Professor of Dermatology, Emory University
Director, Clinical Immunology Laboratory, Emory University Hospital
Co-Director, Image Analysis Core, Emory Digestive Disease Research and Development Center
Graduate Student Recruiter, Immunology and Molecular Pathogenesis Program, Emory University
B.S. Davidson College, - 1980
Ph.D. Emory University School of Medicine
Department of Microbiology and Immunology; Thesis Advisor: Dr. Linda L. Perry, - 1985
M.D. Emory University School of Medicine, - 1986
- Mucosal Immunology; Chemokine Receptors; Lymphoid Organogenesis
The major areas my laboratory studies are: (1) the role of chemokines and chemokine receptors including CCR6, CCR9, and CCR10 in mucosal immunity; and (2) the cellular interactions, cytokines, and chemokines involved in initiating the development of the lymphoid aggregates present in the small intestine including cryptopatches and isolated lymphoid follicles.
The Clinical Immunology Laboratory at Emory University Hospital performs a variety of immunology tests including protein electrophoresis and immunofixation, immunoglobulin and serum protein quantitation by nephelometry, cryoglobulin testing, miscellaneous protein testing, autoantibody detection, infectious disease serology testing, and measurement of a variety of analytes on automated immunoassay platforms. The laboratory also plays a major role in serological testing of samples from tissue and organ donors. A medical technician from the laboratory is on call at all times to perform stat infectious disease serology testing on samples from organ donors prior to transplantation. The immunology laboratory also supports specific types of surgery that require intraoperative immunoassays down with a short turn around time (most commonly this is testing for parathyroid hormone or PTH in patients with hyperparathyroidism).
In addition to my administrative role in the laboratory, I also do the physician interpretations of protein electrophoresis and immunofixation testing. Interpretation of protein electrophoresis and immunofixation tests as well as some autoantibody testing (primarily anti-neutrophil cytoplasmic antibody or ANCA testing) is done with the assistance of CP residents who rotate for one month on the clinical immunology service. Drs. Charlie Hill and Alexis Carter also take turns signing out these cases that need physician interpretations. Serum protein electrophoresis and immunofixation are performed to detect the presence of monoclonal immunoglobulin species (also known as paraproteins) in patients with plasma cell dyscrasias including multiple myeloma, amyloidosis, and monoclonal gammopathy of undetermined significance. Other diseases associated with paraproteins are Waldenstroms macroglobulinemia and some types of B cell lymphoma. Patients with monoclonal gammopathies are monitored during their therapy using the paraprotein levels as an index of residual tumor burden. CSF protein electrophoresis is used to detect oligoclonal IgG bands associated with multiple sclerosis and other immunologically-mediated demyelinating diseases. The Emory immunology laboratory has recently introduced a more sensitive isoelectric focusing method for the detection of oligoclonal IgG bands.
Janet and Elvin Price Award, Crohns & Colitis Foundation of America, 2002-2004
Poster of Distinction Award, 2001 Digestive Disease Week, 2001
Travel Award to Ninth Immunology Congress, American, 1995
Dermatology Foundation Career Development Award, 1994-1997
Thomas B. Fitzpatrick Research Award, Kao Corporation, 1994
Fellow, College of American Pathologists, 1991-present
Alpha Omega Alpha, Emory University School of Medicine, 1986
Cum Laude Graduate, Emory University School of Medicine, 1986
Magna Cum Laude Graduate, Davidson College, 1980
Election to Phi Beta Kappa, Davidson College, 1980
National Merit Scholar, 1976
1989 American Board of Pathology Certification in Anatomic Pathology (9/28/89)
Wang J, Dong Y, Sun JZ, Taylor RT, Guo C, Alegre ML, Williams IR, Newell KA. 2006. Donor lymphoid organs are a major site of alloreactive T cell priming following intestinal transplantation. Am. J. Transplant., 2006 Sep 4; Epub ahead of print, PMID: 16952298.
Williams IR. 2006. CCR6 and CCL20: partners in intestinal immunity and lymphorganogenesis. Ann. NY Acad. Sci., 1072:52-61.
Schnell FJ, Zoller AL, Patel S, Williams IR, Kersh GJ. 2006. Early growth response gene 1 provides negative feedback to inhibit entry of progenitor cells into the thymus. J. Immunol., 176:4740-4747.
Talsma SS, Babensee JE, Murthy N, Williams IR. 2006. Development and in vitro validation of a targeted delivery vehicle for DNA vaccines. J. Control. Release, 112:271-279, 2006.
Salazar-Gonzalez RM, Niess JH, Zammit DJ, Ravindran R, Srinivasan A, Maxwell JR, Stoklasek T, Yadav R, Williams IR, Gu X, McCormick BA, Pazos MA, Vella AT, Lefrancois L, Reinecker HC, McSorley, SJ. 2006. CCR6-mediated dendritic cell activation of pathogen-specific T cells in Peyer's patches. Immunity, 24:623-632.
Stover EH, Chen J, Folens C, Lee BH, Mentens N, Marynen P, Williams IR, Gilliland DG, Cools J. 2006 Activation of FIP1L1-PDGFR¿ requires disruption of the juxtamembrane domain of PDGFR and is FIL1L1 independent. Proc. Natl. Acad. Sci. USA, 103:8078-8083.
Chan IT, Kutok JL, Williams IR, Cohen S, Moore S, Shigematsu H, Ley TJ, Akashi K, LeBeau MM, Gilliland DG. 2006 Oncogenic K-ras cooperates with PML-RAR¿ to induce an acute promyelocytic leukemia-like disease. Blood, 108:1708-1715.
Sanders CJ, Yu Y, Moore DA III, Williams IR, Gewirtz AT. 2006. Humoral immune response to flagellin requires T-cells and activation of innate immunity. J. Immunol., 177:2810-2818.
Taylor RT, Williams IR. 2005. Lymphoid organogenesis in the intestine. Immunol. Res., 33:167-181.
Chen J, Lee BH, Williams IR, Kutok JL, Mitsiades CS, Duclos N, Cohen S, Adelsperger J, Okabe R, Coburn A, Moore S, Huntly BJ, Fabbro D, Anderson KC, Griffin JD, Gilliland DG. 2005. FGFR3 as a therapeutic target of the small molecule inhibitor PKC412 in hematopoietic malignancies. Oncogene, 24:8259-8267.
Lee BH, Williams IR, Anastasiadou E, Boulton CL, Wojiski S, Amaral SM, Curley DP, Duclos N, Huntly B, Fabbro D, Griffin JD, Gilliland DG. 2005. FLT3 internal tandem duplication mutations induce myeloproliferative or lymphoid disease in a transgenic mouse model that responds to the FLT3 inhibitor PKC412. Oncogene, 24:7882-7892.
Growney JD, Shigematsu H, Li Z, Lee BH, Adelsperger J, Rowan R, Curley DP, Akashi K, Williams IR, Speck N, Gilliland DG. 2005. Loss of Runx1 perturbs adult hematopoiesis and is associated with a myeloproliferative phenotype. Blood, 106:494-504.
Chen J, Williams IR, Lee BH, Duclos N, Huntly BJP, Donoghue DJ, Gilliland DG. 2005. Constitutively activated FGFR3 mutants signal through PLC¿-dependent and -independent pathways for hematopoietic transformation. Blood, 106:328-337.
L¿gering A, Floer M, Maaser C, Spahn TW, Schmidt MA, Domschke W, Williams IR, Kucharzik T. 2005. CCR6 is mandatory for CD4+ regulatory T cell development and M cell formation inside Peyers patches. Am. J. Pathol., 166:1647-1654.
Klapproth JA, Sasaki M, Sherman M, Babbin B, Donnenberg MS, Fernandes PJ, Scaletsky ICA, Kalman D, Nusrat A, Williams IR. 2005. C. rodentium lifA/efa1 is essential for colonic colonization and crypt cell hyperplasia in vivo. Infect. Immun., 73:1441-1451.
Mohi MG, Williams IR, Dearolf CR, Chan G, Kutok JL, Cohen S, Morgan K, Boulton C, Shigematsu H, Keilhack H, Akashi K, Gilliland DG, Neel BG. 2005. Prognostic, therapeutic and mechanistic implications of mouse model of leukemia evoked by Shp2 (PTPN11) mutations. Cancer Cell, 7:179-191.
Sitaraman SV, Klapproth J, Moore D, Landers C, Targan S, Williams IR, Gewirtz AT. 2005. Elevated flagellin-specific immunoglobulins in Crohn's disease. Am. J. Physiol. Gastrointest. Liver Physiol., 288:G403-G406.
Kucharzik T, Hudson JT III, L¿gering A, Abbas JA, Bettini M, Evans ME, Ziegler TR, Merlin D, Madara JL, Williams IR. 2005. Acute induction of human IL-8 production by intestinal epithelium triggers neutrophil infiltration without mucosal injury. Gut, 54:1565-1572.
Huntly BJP, Shigematzu H, Deguchi K, Lee B, Mizuno S, Duclos N, Rowan R, Amaral S, Curley D, Williams IR, Akashi K, Gilliland DG. 2004. MOZ-TIF2, but not BCR-ABL, confers properties of leukemic stem cells to committed murine hematopoietic progenitors. Cancer Cell, 6:587-596.
Taylor RT, Lugering A, Newell KA, Williams IR. 2004. Intestinal cryptopatch formation in mice requires lymphotoxin ¿ and the lymphotoxin ¿ receptor. J. Immunol., 173:7183-7189.
Chen J, DeAngelo DJ, Kutok JL, Williams IR, Lee BH, Wadleigh M, Duclos N, Cohen S, Adelsperger J, Okabe R, Coburn A, Galinsky I, Huntly B, Cohen P, Meyer T, Fabbro D, Roesel J, Banerji L, Griffin JD, Xiao S, Fletcher JA, Stone RM, Gilliland DG. 2004. PKC inhibits the ZNF198-FGFR1 fusion tyrosine kinase and is efficacious in treatment of stem cell myeloproliferative disease associated with t(8;13)(p11;q12). Proc. Nat. Acad. Sci. USA, 101:14479-14484.
Araki T, Mohi MG, Ismat FA, Bronson RT, Williams IR, Kutok JL, Yang W, Pao LI, Gilliland DG, Epstein JA, Neel BG. 2004. Mouse model of Noonan syndrome reveals cell type-and gene dosage-dependent effects of Ptpn11 mutation. Nat. Med., 10:849-857.
Chen J, Williams IR, Kutok JL, Duclos N, Anastasiadou E, Masters SC, Fu H, Gilliland DG. 2004. Positive and negative regulatory roles of the WW-like domain in TEL/PDGF¿R transformation. Blood, 104:535-542.
Chan IT, Kutok JL, Williams IR, Cohen S, Kelly L, Shigematsu H, Johnson L, Akashi K, Tuveson DA, Jacks T, Gilliland DG. 2004. Conditional expression of oncogenic K-ras from its endogenous promoter induces a myeloproliferative disease. J. Clin. Invest. 113:528-538.
Williams IR. 2004. Chemokine receptors and leukocyte trafficking in the mucosal immune system. Immunol. Res., 29:283-292.
Kucharzik T, Gewirtz T, Merlin D, Madara JL, Williams IR. 2003. Lateral membrane lipoxin A4 receptors mediate LXA4s anti-inflammatory action on intestinal epithelial cells. Amer. J. Physiol.-Cell, 284:C888-C896.
Deguchi K, Ayton PM, Carapeti M, Kutok JL, Snyder CS, Williams IR, Cross NCP, Glass CK, Cleary ML, Gilliland DG. 2003. MOZ-TIF2-induced acute myeloid leukemia requires the MOZ nucleosome binding motif and TIF2-mediated recruitment of CBP. Cancer Cell, 3:1-13.
Cools J, Stover EH, Boulton CL, Gotlib J, Legare RD, Amaral SM, Duclos N, Rowan R, Curley DP, Kutok JL, Lee, BH,Williams IR, Coutre SE, Stone RM, DeAngelo DJ, Marynen P, Meyer, T, Fabbro D, Neuberg D, Weisberg E, Griffin JD, Gilliland DG. 2003. PKC412 overcomes resistance to imanitib in a murine model of FIP1L1-PDGFR¿-induced myeloproliferative disease. Cancer Cell, 3:459-469.
L¿gering A, Kucharzik T, Soler D, Picarella D, Hudson JT III, Williams IR. 2003. T lymphocyte precursors undergoing extrathymic differentiation in intestinal cryptopatches express CCR6. J. Immunol., 171:2208-2215.
Zhao X, Sato A, Dela Cruz CS, Linehan M, Luegering A, Kucharzik T, Shirakawa A, Marquez G, Farber J, Williams I, Iwasaki A. 2003. CCL9 is secreted by the follicle associated epithelium and recruits dome region Peyers patch CD11b+ dendritic cells. J. Immunol., 171:2797-2803.
Kucharzik T, Williams IR. 2002. Neutrophil migration across the intestinal epithelial barrier: summary of in vitro data and description of a new transgenic mouse model with doxycycline-inducible IL-8 expression in intestinal epithelial cells. Pathobiology, 70:143-149.
Liu Y, Buehring H-J, Burst SL, Williams IR, Parkos, CA. 2002. Signal regulatory protein (SIRP¿), a cellular ligand for CD47, regulates PMN transmigration. J. Biol. Chem. 277:10028-10036.
Gewirtz AT, Collier-Hyams LS, Young A,N Kucharzik T, Guilford WJ, Parkinson JF, Williams IR, Neish AS, Madara JL. 2002. Lipoxin A4 analogs attenuate intestinal epithelial proinflammatory gene expression and reduce the severity of dextran sodium sulfate-induced colitis. J. Immunol. 168:5260-5267.
Schon MP, Schon M, Parker CM, Williams IR. 2002. Dendritic epidermal T cells (DETC) are diminished in integrin alphaE(CD103)-deficient mice. J. Invest. Dermatol. 119:190-193.
Kelly LM, Kutok JL, Williams IR, Boulton CL, Amaral S, Curley DP, Ley TJ, Gilliland DG. 2002. PML/RAR¿ and FLT3-ITD induce an APL-like disease in a mouse model. Proc. Natl. Acad. Sci. USA, 99:8283-8288.
Dash AJ, Williams IR, Kutok J, Tomasson MH, Anastasiadou E, Lindahl K, Li S, Van Etten RA, Borrow J, Housman D, Druker B, Gilliland DG. 2002. A murine model of CML blast crisis induced by cooperation between BCR/ABL and NUP98/HOXA9. Proc. Natl. Acad. Sci. USA, 99:7622-7677.
Kelly LM, Yu JC, Boulton CL, Apatira M, Li J, Sullivan CM, Williams IR, Amaral S, Curley DP, Duclos N, Neuberg D, Scarborough R, Pandey A, Hollenbach S, Abe K, Lokker NA, Gilliland DG, Giese NA. 2002. CT53518, a novel selective FLT3 antagonist for the treatment of acute myelogenous leukemia (AML). Cancer Cell, 1:421-432.
Kucharzik T, Hudson JT III, Waikel RL, Martin WD, Williams IR. 2002. CCR6 expression distinguishes mouse myeloid and lymphoid dendritic cell subsets: demonstration using a CCR6 EGFP knock-in mouse. Eur. J. Immunol., 32:104-112.
Kelly LM, Liu Q, Kutok J, Williams IR, Boulton CL, Gilliland DG. 2002. Flt3 internal tandem duplication mutations associated with human acute myeloid leukemias induce myeloproliferative disease in a murine bone marrow transplant model. Blood, 99:310-318.
Schwaller J, Anastasiadou E, Cain D, Kutok J, Wojiski S, Williams IR, Sternberg DW, LaStarva R, Cresecenzi B, Sternberg DW, Andreasson P, Schaivo R, Siena S, Mecucci C, Gilliland DG. 2001. H4 (D10S170), a gene frequently rearranged in papillary thyroid carcinoma is fused to the platelet-derived growth factor receptor ¿ gene in atypical chronic myeloid leukemia with t(5:10)(q33;q22). Blood, 97:3910-3918.
Roye O, Delacre M, Williams IR, Auriault C, Wolowczuk I. 2001. Cutaneous interleukin-7 transgenic mice display a propitious environment to Schistosoma mansoni infection. Parasite Immunology, 23:133-140.
Merlin D, Si-Tahar,M, Sitaraman SV, Eastburn K, Williams I, Liu X, Hediger MA, and Madara JL. 2001. Colonic epithelial hPepT1 expression occurs in inflammatory bowel disease: transport of bacterial peptides influences expression of MHC class I molecules. Gastroenterology, 120:1666-1679.
Tomasson MH, Williams IR, Li S, Kutok J, Cain D, Gillessen S, Dranoff G, Van Etten RA, Gilliland DG. 2001. Induction of myeloproliferative disease in mice by tyrosine kinase fusion oncogenes does not require granulocyte-macrophage colony-stimulating factor or interleukin-3. Blood, 97:1435-1441.
Tomasson MH, Sternberg DW, Williams IR, Carroll M, Cain D, Aster JC, Ilaria RL, Van Etten RA, Gilliland DG. 2000. Fatal myeloproliferation, induced in mice by TEL/PDGF¿R expression, depends on PDGF¿R tyrosines 579/581. J. Clin. Invest. 105:423-432.
Liu Q, Schwaller J, Kutok J, Cain D, Aster JC, Williams IR, Gilliland DG. 2000. Signal transduction and transforming properties of the TEL-TRKC fusions associated with t(12;15)(p13;q25) in congenital fibrosarcoma and acute myelogenous leukemia. EMBO J. 19:1827-1838.
Doering CB, Williams IR, Danner DJ. 2000. Controlled overexpression of BCKD kinase expression: metabolic engineering applied to BCAA metabolism in a mammalian system. Metab. Eng. 2:349-356.
Schwaller J, Parganas E, Wang D, Cain D, Aster JC, Williams IR, Lee CK, Gerthner R, Kitamura T, Frantsve J, Anastasiadou E, Loh ML, Levy DE, Ihle JN, Gilliland DG. 2000. Stat5 is essential for the myelo- and lymphoproliferative disease induced by TEL/JAK2. Molecular Cell, 6:693-704.
Tomasson MH, Williams IR, Hasserjian R, Udomsakdi C, McGrath SM, Schwaller J, Druker B, Gilliland DG. 1999. TEL-PDGF¿R induces hematologic malignancies in mice that respond to a specific tyrosine kinase inhibitor. Blood, 93:1707-1714.
Rauschmayr-Kopp T, Williams IR, Borriello F, Sharpe AH, Kupper TS. 1998. Distinct roles for B7-1 and B7-2 costimulation in immune responses to epicutaneous antigen. Eur. J. Immunol. 28:4221-4227.
Schwaller J, Frantsve J, Aster J, Williams IR, Tomasson MH, Ross TS, Peeters P, Van Rompey L, Marynen P, Van Etten RA, Ilaria R Jr., Marynen P, Gilliland DG. 1998. Transformation of hematopoietic cell lines to growth-factor independence and induction of a fatal myelo- and lymphoproliferative disease in mice by retrovirally transduced TEL/JAK2 fusion genes. EMBO J. 17:5321-5333.
Williams IR, Rawson EA, Manning L, Karaoli T, Rich BE, Kupper TS. 1997. IL-7 overexpression in transgenic mouse keratinocytes causes a lymphoproliferative skin disease dominated by intermediate TCR cells: evidence for a hierarchy in IL-7 responsiveness among cutaneous T cells. J. Immunol. 159:3044-3056.
Williams IR, Ort RJ, Daley D, Manning L, Karaoli T, Barnhill RL, Kupper TS. 1996. Constitutive expression of B7-1 (CD80) on mouse keratinocytes does not prevent development of chemically induced skin papillomas and carcinomas. J. Immunol. 156:3382-3388.
Groves RW, Rauschmayr T, Nakamura K, Sarkar S, Williams IR, Kupper TS. 1996. Inflammatory and hyperproliferative skin disease in mice that express elevated levels of the IL-1 receptor (type I) on epidermal keratinocytes. Evidence that IL-1-inducible secondary cytokines produced by keratinocytes in vivo can cause skin disease. J. Clin. Invest. 98:336-344.
Williams IR, Kupper TS. 1996. Immunity at the surface: homeostatic mechanisms of the skin immune system. Life Sciences, 58:1485-1507.
Nakamura K, Williams IR, Kupper TS. 1995. Keratinocyte-derived monocyte chemoattractant protein 1 (MCP-1): Analysis in a transgenic model demonstrates MCP-1 can recruit dendritic cells and Langerhans cells to skin. J. Invest. Dermatol. 105:635-643.
Williams IR, Kupper TS. 1994. Epidermal ICAM-1 is not a primary inducer of cutaneous inflammation in transgenic mice. Proc. Natl. Acad. Sci. USA, 91:9710-9714.
Xu H, Gonzalo JA, St.Pierre Y, Williams IR, Kupper TS, Cotran RS, Springer TA, Gutierrez-Ramos, J-C. 1994. Leukocytosis and resistance to septic shock in ICAM-1 deficient mice. J. Exp. Med. 180:95-109.
Williams IR, Ort RJ, Kupper TS. 1994. Keratinocyte expression of B7-1 in transgenic mice amplifies the primary immune response to cutaneous antigens. Proc. Natl. Acad. Sci. USA, 91:12780-12784.
Turksen K, Kupper T, Degenstein L, Williams I, Fuchs E. 1992. IL-6: Insights into its function in skin and psoriasis by expression in transgenic mice. Proc. Natl. Acad. Sci. USA, 89:5068-5072.
Williams IR, Unanue ER. 1991. Characterization of accessory cell costimulation of Th1 cytokine synthesis. J. Immunol. 147:3752-3760.
Williams IR, Unanue ER. 1990. Costimulatory requirements of murine Th1 clones: the role of accessory-cell derived signals in responses to anti-CD3 antibody. J. Immunol. 145:85-93.
Schwartz B, Glazer H, Williams IR. 1989. Clinicopathological conference: Headache, mental status changes, and death in a 36-year-old woman with lupus. Am. J. Med. 86:94-102.
Perry LL, Williams IR, Shelby J. 1986. Anti-I-A immunotherapy in transplantation: inhibition of skin and heart transplant rejection by induction of donor-specific immunosuppression. Transplant. Proc. 18:910-912.
Williams IR, Perry LL. 1985. Prolongation of allograft survival by immunotherapy with monoclonal antibodies against host class II MHC molecules. Transplant. Proc. 17:985-988.
Williams IR, Perry LL. 1985. A double determinant solid-phase immunoassay for measurement of serum levels of monoclonal anti-I-A antibody in mice receiving anti-Ia immunotherapy. J. Immunol. Methods, 85:279-294.
Perry LL, Williams IR. 1985. Regulation of transplantation immunity in vivo by monoclonal antibodies recognizing host class II restriction elements. I. Genetics and specificity of anti-Ia immunotherapy in murine skin allograft recipients. J. Immunol. 134:2935-2941.
Williams IR, Perry LL. 1985. Regulation of transplantation immunity in vivo by monoclonal antibodies recognizing host class II restriction elements. II. Effects of anti-Ia immunotherapy on host T cell responses to graft alloantigens. J. Immunol. 134:2942-2947.
Perry LL, Williams IR, DiRusso S. 1984. Suppressor T cell recognition of major and minor histocompatibility alloantigens: selected suppression of MHC-directed responses by minor alloantigen Ts. J. Immunol. 133:16-23.
Beck WF, Schuh MD, Williams IR. 1981. Phosphorescence and energy assignment of acetaldehyde-d4 (3A") in the vapor phase. Chem. Phys. Lett. 81:435-438.
Cebul FB, Kirk KA, Lupo DW, Pittinger LM, Schuh, MD, Williams IR, Winston, GC. 1980. Charge-transfer mechanism for quenching of the lowest 3n, ¿* state of vapor-phase carbonyl-containing compounds by O2. J. Am. Chem. Soc. 102:5656-5661.
Williams IR, Rich BE, Kupper TS. 2003. Chapter 26: Cytokines. In Dermatology in General Medicine, Eds. IM Freedberg, AZ Eisen, K Wolff, KF Austen, LA Goldsmith, and SI Katz. 6th Edition, McGraw-Hill Co., New York.
Williams IR, Rich BE, Kupper TS. 1999. Chapter 30: Cytokines and chemokines. In Dermatology in General Medicine, Ed. TB Fitzpatrick, 5th Edition, McGraw-Hill Co., New York.
Williams IR. 1998. Fibroblasts. In Encyclopedia of Immunology, 2nd Edition, Eds. PJ Delves and IM Roitt, Academic Press, London.