DF/HCC Program Affiliation

Cutaneous Oncology and Melanoma, Co-Leader
Cancer Immunology
Lymphoma and Myeloma

DF/HCC Associations

Principal Investigator, Skin Cancer SPORE
Member, Center Scientific Council

Research Abstract

Dr. Kupper’s research has focused on epidermal and T cell cytokines, adhesion molecules, dendritic cells and T cell homing, and the interface between acquired and innate immunity in the skin. He initiated several transgenic approaches to the study of skin immunopathophysiology His current research focus also includes cutaneous oncology, with active translational research programs in Cutaneous T Cell Lymphoma, dendritic cell immunobiology, and vaccine therapy. Dr. Kupper has a long track record of outstanding research accomplishments. He is the principal investigator on the NCI SPORE in Skin Cancer grant, awarded in 2001. Dr. Kupper has served as Director of the Harvard Skin Disease Research Center (HSDRC) since its initial funding in 1994. In addition to his role as Director of the HSDRC, he is currently the principal investigator on a MERIT award from the NIAID, as well as PI on five other NIH grants from NCI, NIAID, and NIAMS, including the Harvard Medical School Department of Dermatology’s training grant. He is the co-leader of the Cutaneous Oncology/Melanoma Program in the DFHCC

Publications

• 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 Jan 17;451(7176):345-9.
  18202660
• 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 2008 Jan;121(1):148-157.e3.
  17910894
• Shin J, Monti S, Aires DJ, Duvic M, Golub T, Jones DA, Kupper TS.Lesional gene expression profiling in cutaneous T-cell lymphoma reveals natural clusters associated with disease outcome.Blood 2007 Oct 15;110(8):3015-27.
  17638852
• 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 Oct 1;177(7):4488-94.
  16982885
• Clark RA, Chong B, Mirchandani N, Brinster NK, Yamanaka K, Dowgiert RK, Kupper TS.The vast majority of CLA+ T cells are resident in normal skin.J Immunol 2006 Apr 1;176(7):4431-9.
  16547281
• Yamanaka K, Clark R, Dowgiert R, Hurwitz D, Shibata M, Rich BE, Hirahara K, Jones DA, Eapen S, Mizutani H, Kupper TS.Expression of interleukin-18 and caspase-1 in cutaneous T-cell lymphoma.Clin Cancer Res 2006 Jan 15;12(2):376-82.
  16428475
• Yamanaka K, Clark R, Rich B, Dowgiert R, Hirahara K, Hurwitz D, Shibata M, Mirchandani N, Jones DA, Goddard DS, Eapen S, Mizutani H, Kupper TS.Skin-derived interleukin-7 contributes to the proliferation of lymphocytes in cutaneous T-cell lymphoma.Blood 20
  16322477
• Yamanaka K, Yawalkar N, Jones DA, Hurwitz D, Ferenczi K, Eapen S, Kupper TS.Decreased T-cell receptor excision circles in cutaneous T-cell lymphoma.Clin Cancer Res 2005 Aug 15;11(16):5748-55.
  16115912
• Adams AE, Zwicker J, Curiel C, Kadin ME, Falchuk KR, Drews R, Kupper TS.Aggressive cutaneous T-cell lymphomas after TNFalpha blockade.J Am Acad Dermatol 2004 Oct;51(4):660-2.
  15389210
• Kupper TS, Fuhlbrigge RC.Immune surveillance in the skin: mechanisms and clinical consequences.Nat Rev Immunol 2004 Mar;4(3):211-22.
  15039758
• Jansing PJ, Chanda R, Gore C, Küpper T.Profiles of occupational exposure in patients with wood dust-induced nasal carcinoma.Int J Occup Med Environ Health 2003;16(4):329-35.
  14964642
• 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
  14734737
• Hurwitz DJ, Pincus L, Kupper TS.Imiquimod: a topically applied link between innate and acquired immunity.Arch Dermatol 2003 Oct;139(10):1347-50.
  14568839
• Dimitroff CJ, Kupper TS, Sackstein R.Prevention of leukocyte migration to inflamed skin with a novel fluorosugar modifier of cutaneous lymphocyte-associated antigen.J Clin Invest 2003 Oct;112(7):1008-18.
  14523038
• Robert C, Klein C, Cheng G, Kogan A, Mulligan RC, von Andrian UH, Kupper TS.Gene therapy to target dendritic cells from blood to lymph nodes.Gene Ther 2003 Aug;10(17):1479-86.
  12900763
• Ferenczi K, Yawalkar N, Jones D, Kupper TS.Monitoring the decrease of circulating malignant T cells in cutaneous T-cell lymphoma during photopheresis and interferon therapy.Arch Dermatol 2003 Jul;139(7):909-13.
  12873887
• Yawalkar N, Ferenczi K, Jones DA, Yamanaka K, Suh KY, Sadat S, Kupper TS.Profound loss of T-cell receptor repertoire complexity in cutaneous T-cell lymphoma.Blood 2003 Dec 1;102(12):4059-66.
  12829591
• Murphy JE, Morales RE, Scott J, Kupper TS.IL-1 alpha, innate immunity, and skin carcinogenesis: the effect of constitutive expression of IL-1 alpha in epidermis on chemical carcinogenesis.J Immunol 2003 Jun 1;170(11):5697-703.
  12759452
• Ferenczi K, Fuhlbrigge RC, Pinkus J, Pinkus GS, Kupper TS.Increased CCR4 expression in cutaneous T cell lymphoma.J Invest Dermatol 2002 Dec;119(6):1405-10.
  12485447
• 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 Jun 1;168(11):5645-51.
  12023362
• Chauhan D, Auclair D, Robinson EK, Hideshima T, Li G, Podar K, Gupta D, Richardson P, Schlossman RL, Krett N, Chen LB, Munshi NC, Anderson KC.Identification of genes regulated by dexamethasone in multiple myeloma cells using oligonucleotide arrays.Oncogen
  11857078
• 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 glycoprotei
  11806998
• Armerding D, Fuhlbrigge RC, Kieffer JD, Kupper TS.Tonsillar B cells do not express PSGL-1, but a significant fraction displays the cutaneous lymphocyte antigen and exhibits effective E- and P-selectin ligand activity.Int Arch Allergy Immunol 2001 Sep;126(
  11641609
• Cheng EH, Wei MC, Weiler S, Flavell RA, Mak TW, Lindsten T, Korsmeyer SJ.BCL-2, BCL-X(L) sequester BH3 domain-only molecules preventing BAX- and BAK-mediated mitochondrial apoptosis.Mol Cell 2001 Sep;8(3):705-11.
  11583631
• Kopp T, Kieffer JD, Rot A, Strommer S, Stingl G, Kupper TS.Inflammatory skin disease in K14/p40 transgenic mice: evidence for interleukin-12-like activities of p40.J Invest Dermatol 2001 Sep;117(3):618-26.
  11564168
• Rich BE, Kupper TS.Cytokines: IL-20 - a new effector in skin inflammation.Curr Biol 2001 Jul 10;11(13):R531-4.
  11470428
• Kieffer JD, Fuhlbrigge RC, Armerding D, Robert C, Ferenczi K, Camphausen RT, Kupper TS.Neutrophils, monocytes, and dendritic cells express the same specialized form of PSGL-1 as do skin-homing memory T cells: cutaneous lymphocyte antigen.Biochem Biophys R
  11453631
• Cheng SX, Kupper T.A new rexinoid for cutaneous t-cell lymphoma.Arch Dermatol 2001 May;137(5):649-52.
  11346343
• Rossiter H, Beissert S, Mayer C, Schön MP, Wienrich BG, Tschachler E, Kupper TS.Targeted expression of bcl-2 to murine basal epidermal keratinocytes results in paradoxical retardation of ultraviolet- and chemical-induced tumorigenesis.Cancer Res 2001 May
  11325830
• Casellas R, Shih TA, Kleinewietfeld M, Rakonjac J, Nemazee D, Rajewsky K, Nussenzweig MC.Contribution of receptor editing to the antibody repertoire.Science 2001 Feb 23;291(5508):1541-4.
  11222858
• de Alboran IM, O'Hagan RC, Gärtner F, Malynn B, Davidson L, Rickert R, Rajewsky K, DePinho RA, Alt FW.Analysis of C-MYC function in normal cells via conditional gene-targeted mutation.Immunity 2001 Jan;14(1):45-55.
  11163229
• Kupper TS.T cells, immunosurveillance, and cutaneous immunity.J Dermatol Sci 2000 Dec;24 Suppl 1:S41-5.
  11137395
• Claas C, Stipp CS, Hemler ME.Evaluation of prototype transmembrane 4 superfamily protein complexes and their relation to lipid rafts.J Biol Chem 2001 Mar 16;276(11):7974-84.
  11113129
• Müller-Röver S, Rossiter H, Paus R, Handjiski B, Peters EM, Murphy JE, Mecklenburg L, Kupper TS.Overexpression of Bcl-2 protects from ultraviolet B-induced apoptosis but promotes hair follicle regression and chemotherapy-induced alopecia.Am J Pathol 2000
  10751363
• Murphy JE, Robert C, Kupper TS.Interleukin-1 and cutaneous inflammation: a crucial link between innate and acquired immunity.J Invest Dermatol 2000 Mar;114(3):602-8.
  10692124
• Frieling UM, Schaumberg DA, Kupper TS, Muntwyler J, Hennekens CH.A randomized, 12-year primary-prevention trial of beta carotene supplementation for nonmelanoma skin cancer in the physician's health study.Arch Dermatol 2000 Feb;136(2):179-84.
  10677093
• Robert C, Kupper TS.Inflammatory skin diseases, T cells, and immune surveillance.N Engl J Med 1999 Dec 9;341(24):1817-28.
  10588968
• Armerding D, Kupper TS.Functional cutaneous lymphocyte antigen can be induced in essentially all peripheral blood T lymphocytes.Int Arch Allergy Immunol 1999 Jul;119(3):212-22.
  10436393
• Robert C, Fuhlbrigge RC, Kieffer JD, Ayehunie S, Hynes RO, Cheng G, Grabbe S, von Andrian UH, Kupper TS.Interaction of dendritic cells with skin endothelium: A new perspective on immunosurveillance.J Exp Med 1999 Feb 15;189(4):627-36.
  9989977
• Rauschmayr-Kopp T, Williams IR, Borriello F, Sharpe AH, Kupper TS.Distinct roles for B7 costimulation in contact hypersensitivity and humoral immune responses to epicutaneous antigen.Eur J Immunol 1998 Dec;28(12):4221-7.
  9862359
• Freeman GJ, Cardoso AA, Boussiotis VA, Anumanthan A, Groves RW, Kupper TS, Clark EA, Nadler LM.The BB1 monoclonal antibody recognizes both cell surface CD74 (MHC class II-associated invariant chain) as well as B7-1 (CD80), resolving the question regarding
  9743327
• Dubin DB, Hurowitz JC, Brettler D, Bernhard JD, Kadin ME, Wallace JE, Woda B, Pihan G, Kupper TS, Harrist TJ.Adnexotropic T-cell lymphoma presenting with generalized anhidrosis, progressive alopecia, pruritus, and Sjögren's syndrome.J Am Acad Dermatol 199
  9520037
• Fuhlbrigge RC, Kieffer JD, Armerding D, Kupper TS.Cutaneous lymphocyte antigen is a specialized form of PSGL-1 expressed on skin-homing T cells.Nature 1997 Oct 30;389(6654):978-81.
  9353122
• Williams IR, Rawson EA, Manning L, Karaoli T, Rich BE, Kupper TS.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 cut
  9300730
• Ayehunie S, Garcia-Zepeda EA, Hoxie JA, Horuk R, Kupper TS, Luster AD, Ruprecht RM.Human immunodeficiency virus-1 entry into purified blood dendritic cells through CC and CXC chemokine coreceptors.Blood 1997 Aug 15;90(4):1379-86.
  9269754
• Rauschmayr T, Groves RW, Kupper TS.Keratinocyte expression of the type 2 interleukin 1 receptor mediates local and specific inhibition of interleukin 1-mediated inflammation.Proc Natl Acad Sci U S A 1997 May 27;94(11):5814-9.
  9159157
• Rossiter H, Alon R, Kupper TS.Selectins, T-cell rolling and inflammation.Mol Med Today 1997 May;3(5):214-22.
  9176884
• Compton CC, Kupper TS, Nadire KB.HIV-infected Langerhans cells constitute a significant proportion of the epidermal Langerhans cell population throughout the course of HIV disease.J Invest Dermatol 1996 Dec;107(6):822-6.
  8941668
• Groves RW, Rauschmayr T, Nakamura K, Sarkar S, Williams IR, Kupper TS.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 cy
  8755642
• Williams IR, Ort RJ, Daley D, Manning L, Karaoli T, Barnhill RL, Kupper TS.Constitutive expression of B7-1 (CD80) on mouse keratinocytes does not prevent development of chemically induced skin papillomas and carcinomas.J Immunol 1996 May 1;156(9):3382-8.
  8617964
• Groves RW, Mizutani H, Kieffer JD, Kupper TS.Inflammatory skin disease in transgenic mice that express high levels of interleukin 1 alpha in basal epidermis.Proc Natl Acad Sci U S A 1995 Dec 5;92(25):11874-8.
  8524866
• Nakamura K, Williams IR, Kupper TS.Keratinocyte-derived monocyte chemoattractant protein 1 (MCP-1): analysis in a transgenic model demonstrates MCP-1 can recruit dendritic and Langerhans cells to skin.J Invest Dermatol 1995 Nov;105(5):635-43.
  7594634
• Ayehunie S, Groves RW, Bruzzese AM, Ruprecht RM, Kupper TS, Langhoff E.Acutely infected Langerhans cells are more efficient than T cells in disseminating HIV type 1 to activated T cells following a short cell-cell contact.AIDS Res Hum Retroviruses 1995 Au
  7492434
• Groves RW, Giri J, Sims J, Dower SK, Kupper TS.Inducible expression of type 2 IL-1 receptors by cultured human keratinocytes. Implications for IL-1-mediated processes in epidermis.J Immunol 1995 Apr 15;154(8):4065-72.
  7706745
• Williams IR, Ort RJ, Kupper TS.Keratinocyte expression of B7-1 in transgenic mice amplifies the primary immune response to cutaneous antigens.Proc Natl Acad Sci U S A 1994 Dec 20;91(26):12780-4.
  7528926
• Alon R, Rossiter H, Wang X, Springer TA, Kupper TS.Distinct cell surface ligands mediate T lymphocyte attachment and rolling on P and E selectin under physiological flow.J Cell Biol 1994 Dec;127(5):1485-95.
  7525609
• Groves RW, Sherman L, Mizutani H, Dower SK, Kupper TS.Detection of interleukin-1 receptors in human epidermis. Induction of the type II receptor after organ culture and in psoriasis.Am J Pathol 1994 Nov;145(5):1048-56.
  7977638
• Mizutani H, Roswit W, Hemperly J, Lawley T, Compton C, Swerlick R, Kupper TS.Human dermal microvascular endothelial cells express the 140-kD isoform of neural cell adhesion molecule.Biochem Biophys Res Commun 1994 Aug 30;203(1):686-93.
  8074723
• Xu H, Gonzalo JA, St Pierre Y, Williams IR, Kupper TS, Cotran RS, Springer TA, Gutierrez-Ramos JC.Leukocytosis and resistance to septic shock in intercellular adhesion molecule 1-deficient mice.J Exp Med 1994 Jul 1;180(1):95-109.
  7911822
• Rossiter H, van Reijsen F, Mudde GC, Kalthoff F, Bruijnzeel-Koomen CA, Picker LJ, Kupper TS.Skin disease-related T cells bind to endothelial selectins: expression of cutaneous lymphocyte antigen (CLA) predicts E-selectin but not P-selectin binding.Eur J I
  7517361
• Ferguson TA, Kupper TS.Antigen-independent processes in antigen-specific immunity. A role for alpha 4 integrin.J Immunol 1993 Feb 15;150(4):1172-82.
  8432974
• Chan BM, Kassner PD, Schiro JA, Byers HR, Kupper TS, Hemler ME.Distinct cellular functions mediated by different VLA integrin alpha subunit cytoplasmic domains.Cell 1992 Mar 20;68(6):1051-60.
  1547502
• Schiro JA, Chan BM, Roswit WT, Kassner PD, Pentland AP, Hemler ME, Eisen AZ, Kupper TS.Integrin alpha 2 beta 1 (VLA-2) mediates reorganization and contraction of collagen matrices by human cells.Cell 1991 Oct 18;67(2):403-10.
  1913826
• Mizutani H, Schechter N, Lazarus G, Black RA, Kupper TS.Rapid and specific conversion of precursor interleukin 1 beta (IL-1 beta) to an active IL-1 species by human mast cell chymase.J Exp Med 1991 Oct 1;174(4):821-5.
  1919436
• Ferguson TA, Mizutani H, Kupper TS.Two integrin-binding peptides abrogate T cell-mediated immune responses in vivo.Proc Natl Acad Sci U S A 1991 Sep 15;88(18):8072-6.
  1896454
• Mizutani H, Black R, Kupper TS.Human keratinocytes produce but do not process pro-interleukin-1 (IL-1) beta. Different strategies of IL-1 production and processing in monocytes and keratinocytes.J Clin Invest 1991 Mar;87(3):1066-71.
  1999487
• Kupper TS.Immune and inflammatory processes in cutaneous tissues. Mechanisms and speculations.J Clin Invest 1990 Dec;86(6):1783-9.
  2254445
• Mizutani H, May LT, Sehgal PB, Kupper TS.Synergistic interactions of IL-1 and IL-6 in T cell activation. Mitogen but not antigen receptor-induced proliferation of a cloned T helper cell line is enhanced by exogenous IL-6.J Immunol 1989 Aug 1;143(3):896-90
  2526177
• Kupper TS.Production of cytokines by epithelial tissues. A new model for cutaneous inflammation.Am J Dermatopathol 1989 Feb;11(1):69-73.
  2644870
• Kupper TS, Lee F, Birchall N, Clark S, Dower S.Interleukin 1 binds to specific receptors on human keratinocytes and induces granulocyte macrophage colony-stimulating factor mRNA and protein. A potential autocrine role for interleukin 1 in epidermis.J Clin
  2460504