Molecular Carcinogenesis Group

Research
Cancer is a complex disease which is often characterized by deregulated intracellular signal transduction. Our long-term goal is to gain insight into signal transduction pathways underlying cancer cell growth and death.

Currently, the Eliopoulos' laboratory engages in three specific areas of research:

1. Regulation of TNF Receptor-associated factor (TRAF) signal transduction.
TRAFs are adaptor molecules which link various receptors and viral proteins to the activation of oncogenic and pro-inflammatory signaling pathways, such as NF-kB and mitogen-activated protein kinases (MAPKs). A major effort in the lab is directed at the identification of novel components of the CD40 and TNF receptor/TRAF signaling networks using yeast-2-hybrid, proteomic and systems biology platforms in combination with molecular and biochemical approaches. Collaborations with European and US research groups support research components of this effort.

2. The role of inflammatory signalling pathways in carcinogenesis.
Epidemiological, clinical and experimental data suggest that a number of human malignancies, such as those of the liver, prostate, colon and lung, can be attributed to toxic agents and irritants or to persistent infections of viral or bacterial aetiology which cause chronic inflammatory imbalance in the affected tissue. We utilize chemical and virus-induced carcinogenesis protocols in knock-out and transgenic animal models to dissect the role of the various cell types present in the tumor microenvironment and analyze the signals exchanged between these cells. In collaboration with clinicians at the University Hospital of Heraklion and biotechnology companies in the UK we also aim to identify molecular signatures of inflammation-associated colon cancer using biopsies from patients. The practical benefits of this research will assist in the improved design of novel anti-cancer therapeutics and diagnostic tools to address prevention, early detection and improved management of human cancer.

3. Exploiting the apoptotic signaling machinery for cancer gene therapy.
The objective of this translational research project is to develop and formulate broad-spectrum therapeutic strategies which can selectively eliminate tumor cells by targeting their apoptosis-regulatory signalling circuits. These efforts are largely directed towards the exploitation of the CD40 pathway for cancer therapy by virtue of its ability to stimulate the host anti-tumor immune response, normalize the tumor microenvironment and directly suppress the growth of CD40-positive tumors. We develop viral vehicles for the efficient and targeted delivery of the CD40 ligand gene to tumors and assess their therapeutic impact either alone or in combination with other agents, including novel antagonists of the anti-apoptotic PI3 kinase/Akt pathway which is frequently activated in human tumors.

Working at the interface of basic and applied molecular biology, we not only aim to understand the mechanisms of carcinogenesis but we also seek to take advantage of this knowledge for the development of more efficient therapies for cancer.