Photo of Robert Fuhlbrigge,  MD, PhD

Robert Fuhlbrigge, MD, PhD

Brigham And Women's Hospital

Brigham And Women's Hospital


rfuhlbrigge@partners.org

Robert Fuhlbrigge, MD, PhD

Brigham And Women's Hospital

EDUCATIONAL TITLES

  • Associate Professor, Dermatology, Harvard Medical School
  • Associate Professor, Pediatrics, Harvard Medical School
  • Vice Chair- Research, Dermatology, Brigham And Women's Hospital
  • Attending Physician, Program in Rheumatology, Boston Children's Hospital

DF/HCC PROGRAM AFFILIATION

Research Abstract

Keywords:

Leukocyte homing

Skin immunology

Skin cancer immunology

The Fuhlbrigge laboratory is currently involved in three primary research projects:

1) Using a unique method for assessment of adhesion to individual T cell glycoproteins developed in the lab, the Fuhlbrigge research group has identified several novel selectin ligands on skin homing T cells. Ongoing studies are directed toward establishing the structural properties of these ligands, characterizing their patterns of expression, defining the mechanisms by which their expression is regulated and correlating expression with specific skin disorders and/or functional T cell subsets. Inhibitory RNA methods are being developed to allow study of the relative contributions of the known E- selectin ligands on T cells.

2) Through examination of tumors from patients with malignant melanoma, the Fuhlbrigge lab has identified a defect in homing receptor expression that may explain the poor prognosis and resistance to immunotherapy seen in these patients. To study these issues, the Fuhlbrigge lab has developed a model of human melanoma growing in human skin transplanted onto immunodeficient mice, which is proving valuable for the study of tumor angiogenesis and the regulation of vascular adhesion receptors in melanoma. This unique strategy will provide not only a method for detailed studies of the mechanisms regulating the recruitment of immune cells to tumors in human tissues, but a means for testing new therapeutic strategies on human tissues that will be more directly applicable to use in real patients than existing models.

3) Although inoculation of skin with vaccinia virus (termed scarification) to prevent smallpox has been used successfully for over 200 years, little is known about the growth of vaccinia virus in skin after inoculation, how scarification promotes activation of the immune response or why this process results in more protective immune responses than more common methods of immunization. The Fuhlbrigge lab, in collaboration with the laboratories of Drs. Kupper and Liu in the Department, is studying how the immune response develops after scarification in mice, and the effects on the response to vaccinia of various cytokines expressed in skin. The Fuhlbrigge lab utilizes unique model for studying scarification, including use of immune deficient mice bearing human skin xenotransplants and mice engineered to overexpress immune modulating cytokines in skin.

Publications

Powered by Harvard Catalyst
  • Bhela S, Kempsell C, Manohar M, Dominguez-Villar M, Griffin R, Bhatt P, Kivisakk-Webb P, Fuhlbrigge R, Kupper T, Weiner H, Baecher-Allan C. Nonapoptotic and extracellular activity of granzyme B mediates resistance to regulatory T cell (Treg) suppression by HLA-DR-CD25hiCD127lo Tregs in multiple sclerosis and in response to IL-6. J Immunol 2015; 194:2180-9. PubMed
  • Vander Lugt B, Tubo NJ, Nizza ST, Boes M, Malissen B, Fuhlbrigge RC, Kupper TS, Campbell JJ. CCR7 plays no appreciable role in trafficking of central memory CD4 T cells to lymph nodes. J Immunol 2013; 191:3119-27. PubMed
  • Chang DK, Sui J, Geng S, Muvaffak A, Bai M, Fuhlbrigge RC, Lo A, Yammanuru A, Hubbard L, Sheehan J, Campbell JJ, Zhu Q, Kupper TS, Marasco WA. Humanization of an anti-CCR4 antibody that kills cutaneous T-cell lymphoma cells and abrogates suppression by T-regulatory cells. Mol Cancer Ther 2012; 11:2451-61. PubMed
  • Purwar R, Schlapbach C, Xiao S, Kang HS, Elyaman W, Jiang X, Jetten AM, Khoury SJ, Fuhlbrigge RC, Kuchroo VK, Clark RA, Kupper TS. Robust tumor immunity to melanoma mediated by interleukin-9-producing T cells. Nat Med 2013. PubMed
  • Li SC, Torok KS, Pope E, Dedeoglu F, Hong S, Jacobe HT, Egla Rabinovich C, Laxer RM, Higgins GC, Lasky A, Baszis K, Becker M, Campillo S, Cartwright V, Cidon M, Inman CJ, Jerath R, O'Neil KM, Vora S, Zeft A, Wallace CA, Ilowite NT, Fuhlbrigge RC. Development of consensus treatment plans for juvenile localized scleroderma. 2012. PubMed
  • Jiang X, Clark RA, Liu L, Wagers AJ, Fuhlbrigge RC, Kupper TS. Skin infection generates non-migratory memory CD8+ TRM cells providing global skin immunity. Nature 2012; 483:227-31. PubMed
  • Tian T, Dubin K, Jin Q, Qureshi A, King SL, Liu L, Jiang X, Murphy GF, Kupper TS, Fuhlbrigge RC. Disruption of TNF-留/TNFR1 Function in Resident Skin Cells Impairs Host Immune Response against Cutaneous Vaccinia Virus Infection. J Invest Dermatol 2012. PubMed
  • Merzaban JS, Burdick MM, Gadhoum SZ, Dagia NM, Chu JT, Fuhlbrigge RC, Sackstein R. Analysis of glycoprotein E-selectin ligands on human and mouse marrow cells enriched for hematopoietic stem/progenitor cells. Blood 2011; 118:1774-83. PubMed
  • Koduru S, Kumar L, Massaad MJ, Ramesh N, Le Bras S, Ozcan E, Oyoshi MK, Kaku M, Fujiwara Y, Kremer L, King S, Fuhlbrigge R, Rodig S, Sage P, Carman C, Alcaide P, Luscinskas FW, Geha RS. Cdc42 interacting protein 4 (CIP4) is essential for integrin-dependent T-cell trafficking. Proc Natl Acad Sci U S A 2010; 107:16252-6. PubMed
  • Yamanaka KI, Fuhlbrigge RC, Mizutani H, Kupper TS. Restoration of peripheral blood T cell repertoire complexity during remission in advanced cutaneous T cell lymphoma. Arch Dermatol Res 2010; 302:453-9. PubMed
  • Ozen S, Fuhlbrigge RC. Update in paediatric vasculitis. Best Pract Res Clin Rheumatol 2009; 23:679-88. PubMed
  • Clark RA, Fuhlbrigge RC. Immunology and skin disease 2009: frontiers in cutaneous immunology. J Invest Dermatol 2009; 129:1849-51. PubMed
  • Bianchi T,Pincus LB,Wurbel MA,Rich BE,Kupper TS,Fuhlbrigge RC,Boes M. Maintenance of peripheral tolerance through controlled tissue homing of antigen-specific T cells in K14-mOVA mice. J Immunol 2009; 182:4665-74. PubMed
  • Sackstein R,Fuhlbrigge R. Western Blot Analysis of Adhesive Interactions under Fluid Shear Conditions: The Blot Rolling Assay. Methods Mol Biol 2009; 536:343-54. PubMed
  • Schatton T, Murphy GF, Frank NY, Yamaura K, Waaga-Gasser AM, Gasser M, Zhan Q, Jordan S, Duncan LM, Weishaupt C, Fuhlbrigge RC, Kupper TS, Sayegh MH, Frank MH. Identification of cells initiating human melanomas. Nature 2008; 451:345-9. PubMed
  • Yamanaka K, Dimitroff CJ, Fuhlbrigge RC, Kakeda M, Kurokawa I, Mizutani H, Kupper TS. Vitamins A and D are potent inhibitors of cutaneous lymphocyte-associated antigen expression. J Allergy Clin Immunol 2007; 121:148-157.e3. PubMed
  • Ota S, Cron RQ, Schanberg LE, O'Neil K, Mellins ED, Fuhlbrigge RC, Feldman BM. Research priorities in pediatric rheumatology: The Childhood Arthritis and Rheumatology Research Alliance (CARRA) consensus. Pediatr Rheumatol Online J 2008; 6:5. PubMed
  • Clark RA, Fuhlbrigge RC. Meeting report of immunology and skin disease: new perspectives. J Invest Dermatol 2007; 127:1838-41. PubMed
  • Alcaide P, King SL, Dimitroff CJ, Lim YC, Fuhlbrigge RC, Luscinskas FW. The 130-kDa glycoform of CD43 functions as an E-selectin ligand for activated Th1 cells in vitro and in delayed-type hypersensitivity reactions in vivo. J Invest Dermatol 2007; 127:1964-72. PubMed
  • Weishaupt C, Munoz KN, Buzney E, Kupper TS, Fuhlbrigge RC. T-cell distribution and adhesion receptor expression in metastatic melanoma. Clin Cancer Res 2007; 13:2549-56. PubMed
  • Fuhlbrigge RC, Weishaupt C. Adhesion molecules in cutaneous immunity. Semin Immunopathol 2007; 29:45-57. PubMed
  • Hirahara K, Liu L, Clark RA, Yamanaka K, Fuhlbrigge RC, Kupper TS. The majority of human peripheral blood CD4+CD25highFoxp3+ regulatory T cells bear functional skin-homing receptors. J Immunol 2006; 177:4488-94. PubMed
  • Liu L, Fuhlbrigge RC, Karibian K, Tian T, Kupper TS. Dynamic programming of CD8+ T cell trafficking after live viral immunization. Immunity 2006; 25:511-20. PubMed
  • Fuhlbrigge RC, King SL, Sackstein R, Kupper TS. CD43 is a ligand for E-selectin on CLA+ human T cells. Blood 2006; 107:1421-6. PubMed
  • Gallego MD, de la Fuente MA, Anton IM, Snapper S, Fuhlbrigge R, Geha RS. WIP and WASP play complementary roles in T cell homing and chemotaxis to SDF-1alpha. Int Immunol 2005; 18:221-32. PubMed
  • Sackstein R, Fuhlbrigge R. The blot rolling assay: a method for identifying adhesion molecules mediating binding under shear conditions. Methods Mol Biol 2006; 341:217-26. PubMed
  • Liu L, Xu Z, Fuhlbrigge RC, Pe. Vaccinia virus induces strong immunoregulatory cytokine production in healthy human epidermal keratinocytes: a novel strategy for immune evasion. J Virol 2005; 79:7363-70. PubMed
  • Kupper TS, Fuhlbrigge RC. Immune surveillance in the skin: mechanisms and clinical consequences. Nat Rev Immunol 2004; 4:211-22. PubMed
  • Chong BF, Murphy JE, Kupper TS, Fuhlbrigge RC. E-selectin, thymus- and activation-regulated chemokine/CCL17, and intercellular adhesion molecule-1 are constitutively coexpressed in dermal microvessels: a foundation for a cutaneous immunosurveillance system. J Immunol 2004; 172:1575-81. PubMed
  • Ferenczi K, Fuhlbrigge RC, Pinkus J, Pinkus GS, Kupper TS. Increased CCR4 expression in cutaneous T cell lymphoma. J Invest Dermatol 2002; 119:1405-10. PubMed
  • Fuhlbrigge RC, King SL, Dimitroff CJ, Kupper TS, Sackstein R. Direct real-time observation of E- and P-selectin-mediated rolling on cutaneous lymphocyte-associated antigen immobilized on Western blots. J Immunol 2002; 168:5645-51. PubMed
  • Pendl GG, Robert C, Steinert M, Thanos R, Eytner R, Borges E, Wild MK, Lowe JB, Fuhlbrigge RC, Kupper TS, Vestweber D, Grabbe S. Immature mouse dendritic cells enter inflamed tissue, a process that requires E- and P-selectin, but not P-selectin glycoprotein ligand 1. Blood 2002; 99:946-56. PubMed
  • Dimitroff CJ, Lee JY, Rafii S, Fuhlbrigge RC, Sackstein R. CD44 is a major E-selectin ligand on human hematopoietic progenitor cells. J Cell Biol 2001; 153:1277-86. PubMed
  • Dimitroff CJ, Lee JY, Fuhlbrigge RC, Sackstein R. A distinct glycoform of CD44 is an L-selectin ligand on human hematopoietic cells. Proc Natl Acad Sci U S A 2000; 97:13841-6. PubMed
Hide