George James Cianciolo

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.