Project Information

Title:

Targeting the hypoxia-inducible transcription factors HIFs in inflammation and cancer.

Principal Investigator:

George Simos, Professor of Biochemistry

Host Laboratory:

Laboratory of Biochemistry, Faculty of Medicine, University of Thessaly

Duration and Budget:

18 months (29/1/2014-31/7/2015), 295.000 €

Administrative Agency:

Research Committee, University of Thessaly

Members of Research Group:

George Simos, Professor of Biochemistry

Eleni Georgatsou, Assoc. Professor of Biochemistry & Molecular Biology

Efrosini Paraskeva, Assoc. Professor of Cellular Physiology

Panagiotis Liakos, Assist. Professor of Medical Biochemistry

Ilias Mylonis, Assist. Professor of Biochemistry

Georgia Chachami, Lecturer of Cellular Biochemistry

Emmanouil Venieris, member of Laboratory & Teaching Staff

Eva Paggou, PhD student

Eleni Triantafyllou, PhD student

Aggeliki Karagiota, PhD student

Short Description:

Hypoxia characterizes major pathological processes such as inflammation and cancer and affects gene expression through the hypoxia-inducible transcription factors HIF-1 and HIF-2. Elucidation of the common and isoform- or tissue-specific mechanisms governing HIFs is important to understand the response of cancer cells to hypoxia and can have novel therapeutic applications. We, therefore, investigate the oxygen-independent regulation of HIFs in cancer cells as well as their connection to tissue inflammation and fibrosis by focusing on:

a. The control of HIFs by phosphorylation and protein-protein interactions in cancer cells. We are trying to identify kinases and phosphatases that modify and regulate HIFs and are developing methods for in situ detection of HIF protein complexes using microscopy.

b. The discovery of new anti-cancer and anti-inflammatory targeted treatment strategies based on HIF inhibition. We aim to generate agents that specifically inhibit phosphorylation of HIF-1alpha and explore their efficiency as anticancer agents.

c. The role of HIFs in hepatocyte lipid metabolism and inflammation, two processes linked in steatohepatitis and hepatocarcinoma. We aim to study the expression profile of key lipogenic enzymes under hypoxic conditions and the role of hypoxia and lipogenesis in the production of hepatocyte proinflammatory cytokines and profibrotic mediators.

The results will provide better insight into the involvement of HIFs in cancer cell survival and proliferation and help identify novel avenues for the development of methods useful for managing cancer, inflammation and common metabolic disorders.