George James Cianciolo, PhD

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Associate Professor Emeritus in Pathology
Department / Division:
Pathology / Pathology Research
Address:
302M/312MA Davison Bldg
Durham, NC 27710
Office Telephone:
(919) 684-8131
Training:
  • PhD, University of Miami, 1977
Research Interests:
My laboratory has two major research interests. The first involves a potent, selective, small-molecule inhibitor of various pro-inflammatory cytokines such as Tumor Necrosis Factor-alpha (TNF) or Monocyte Chemoattractant Protein-1 (MCP-1). This molecule, LMP-420, inhibits the transcription of mRNA for both TNF and MCP-1 as well as other pro-inflammatory chemokines such as Interferon Inducible Protein-10 (IP-10). Pro-inflammatory cytokines/chemokines such as these have been implicated in the pathogenesis of a number of major diseases, including rheumatoid arthritis, Crohn's disease, and psoriasis and are also suspected to play a role in other major diseases including asthma, insulin resistance associated with obesity-related diabetes, cachexia associated with cancer and AIDS, and with the replication of HIV itself. LMP-420 has demonstrated potent anti-inflammatory activity in rodents when delivered by a variety of routes including intraperitoneal and subcutaneous injections, aerosolization, and orally. Recently we identified the potential utility of LMP-420 as an effective and safe therapeutic agent for treatment of B-cell chronic lymphocytic leukemia, multiple myeloma, or other hematological malignancies. Our laboratory studies are aimed at determining both the molecular target(s) and mechanism(s) of action of this novel and potentially clinically-useful cytokine/chemokine inhibitor and for identifying new diseases in which it might have potential utility.
The second area of interest involves a series of novel, viral-related peptides which inhibits vascular leak syndrome. These biologically-active sequences have been well-conserved in nature and are found not only in pathogenic retroviruses but in a number of human endogenous retroviral sequences as well. In an animal model of disseminated intravascular coagulation (DIC), one of these peptides fully protected animals from the lethal consequences of DIC. We are investigating this and related peptides for use in treating or preventing hemorrhagic events in diseases such as dengue hemorrhagic fever. We are in the process of characterizing the mechanism of action of these unique molecules and identifying additional diseases in which they might be utilized.
Representative Publications:
  • Anderson, RB; Cianciolo, GJ; Kennedy, MN; Pizzo, SV. Alpha 2-macroglobulin binds CpG oligodeoxynucleotides and enhances their immunostimulatory properties by a receptor-dependent mechanism. Journal of Leukocyte Biology. 2008;83:381-392.  Abstract
  • Kaczowka, SJ; Madding, LS; Epting, KL; Kelly, RM; Cianciolo, GJ; Pizzo, SV. Probing the stability of native and activated forms of alpha2-macroglobulin. International Journal of Biological Macromolecules. 2008;42:62-67.  Abstract
  • Bond, JE; Cianciolo, GJ; Pizzo, SV. Incorporation of low molecular weight molecules into alpha(2)-macroglobulin by nucleophilic exchange. Biochemical and Biophysical Research Communications. 2007;357:433-438.  Abstract
  • Haraguchi, S; Day, NK; Kamchaisatian, W; Beigier-Pompadre, M; Stenger, S; Tangsinmankong, N; Sleasman, JW; Pizzo, SV; Cianciolo, GJ. LMP-420, a small-molecule inhibitor of TNF-alpha, reduces replication of HIV-1 and Mycobacterium tuberculosis in human cells. AIDS Research and Therapy. 2006;3:8.  Abstract
  • Wassmer, SC; Cianciolo, GJ; Combes, V; Grau, GE. Inhibition of endothelial activation: a new way to treat cerebral malaria?. PLoS Medicine. 2005;2:e245.  Abstract
  • Luangwedchakarn, V; Day, NK; Hitchcock, R; Brown, PG; Lerner, DL; Rucker, RP; Cianciolo, GJ; Good, RA; Haraguchi, S. A retroviral-derived peptide phosphorylates protein kinase D/protein kinase Cmu involving phospholipase C and protein kinase C. Peptides. 2003;24:631-637.  Abstract
  • Liao, HX; Cianciolo, GJ; Staats, HF; Scearce, RM; Lapple, DM; Stauffer, SH; Thomasch, JR; Pizzo, SV; Montefiori, DC; Hagen, M; Eldridge, J; Haynes, BF. Increased immunogenicity of HIV envelope subunit complexed with alpha2-macroglobulin when combined with monophosphoryl lipid A and GM-CSF. Vaccine. 2002;20:2396-2403.  Abstract
  • Cianciolo, GJ; Enghild, JJ; Pizzo, SV. Covalent complexes of antigen and alpha(2)-macroglobulin: evidence for dramatically-increased immunogenicity. Vaccine. 2001;20:554-562.  Abstract
  • Haraguchi, S; Cianciolo, GJ; Good, RA; James-Yarish, M; Brigino, E; Day, NK. Inhibition of interleukin-2 and interferon-gamma by an HIV-1 Nef-encoded synthetic peptide. AIDS. 1998;12:820-823.  Abstract
  • Brigino, E; Haraguchi, S; Koutsonikolis, A; Cianciolo, GJ; Owens, U; Good, RA; Day, NK. Interleukin 10 is induced by recombinant HIV-1 Nef protein involving the calcium/calmodulin-dependent phosphodiesterase signal transduction pathway. Proceedings of the National Academy of Sciences of USA. 1997;94:3178-3182.  Abstract
  • Haraguchi, S; Good, RA; Cianciolo, GJ; Engelman, RW; Day, NK. Immunosuppressive retroviral peptides: immunopathological implications for immunosuppressive influences of retroviral infections. Journal of Leukocyte Biology. 1997;61:654-666.  Abstract
  • Haraguchi, S; Good, RA; James-Yarish, M; Cianciolo, GJ; Day, NK. Induction of intracellular cAMP by a synthetic retroviral envelope peptide: a possible mechanism of immunopathogenesis in retroviral infections. Proceedings of the National Academy of Sciences of USA. 1995;92:5568-5571.  Abstract
  • Cianciolo, GJ. Antiinflammatory effects of neoplasms. Research in Immunology. 1993;144:268-271.  Abstract
  • Haraguchi, S; Good, RA; Cianciolo, GJ; James-Yarish, M; Day, NK. Transcriptional down-regulation of tumor necrosis factor-alpha gene expression by a synthetic peptide homologous to retroviral envelope protein. Journal of Immunology. 1993;151:2733-2741.  Abstract
  • Haraguchi, S; Good, RA; Cianciolo, GJ; Day, NK. A synthetic peptide homologous to retroviral envelope protein down-regulates TNF-alpha and IFN-gamma mRNA expression. Journal of Leukocyte Biology. 1992;52:469-472.  Abstract
  • Laurence, J; Kulkosky, J; Dong, B; Early, E; Snyderman, R; Cianciolo, GJ. A soluble inhibitor of T lymphocyte function induced by HIV-1 infection of CD4+ T cells: characterization of a cellular protein and its relationship to p15E. Cellular Immunology. 1990;128:337-352.  Abstract
  • Cianciolo, GJ; Copeland, TD; Oroszlan, S; Snyderman, R. Inhibition of lymphocyte proliferation by a synthetic peptide homologous to retroviral envelope proteins. Science. 1985;230:453-455.  Abstract
  • Cianciolo, GJ; Kipnis, RJ; Snyderman, R. Similarity between p15E of murine and feline leukaemia viruses and p21 of HTLV. Nature. 1984;311:515.  Abstract