Dr. Dimitrios Iliopoulos’ laboratory studies the inter-complexity between chronic inflammatory diseases such as ulcerative colitis, obesity and cancer and identifies common regulatory circuits and novel drug targets.
The molecular events governing the onset and progression of malignant transformation involve the inactivation of tumor suppressor genes and the acquisition of oncogenic mutations. In addition, the progression to cancer is influenced by environmental conditions and extracellular signaling pathways that affect the activity of tumor suppressors and oncoproteins. Clinical and epidemiological studies have revealed that patients diagnosed with inflammatory and auto-immune diseases show increased incidence and aggressiveness of tumor formation. For example, patients with chronic ulcerative colitis are at increased risk of developing colorectal cancer, while patients with systemic lupus erythematosus have increased risk of developing non-Hodgkin’s lymphoma. These data suggest the inter-complexity between chronic inflammatory and auto-immune diseases and carcinogenesis; however the molecular bases of these links among diseases are poorly understood.
A major focus of Iliopoulos’ research is to identify how extracellular and intracellular inflammatory stimuli contribute to the transformation of normal cells into cancer cells. In particular, he strives to understand how perturbations of the tumor microenvironment contribute to oncogenic transformation and potentially formation and maintenance of cancer stem cell populations. Furthermore, he is planning to develop novel genetically engineered mouse models of inflammatory-induced carcinogenesis. In addition, microRNAs, a novel class of short non-coding RNAs, seem to play an essential role in the pathogenesis of several human diseases. His laboratory is interested in identifying microRNA-gene networks that are essential in human inflammatory diseases and cancer, through integration of genomic and proteomic data using novel bioinformatic algorithms.
Selected Cancer-Related Publications:
Hatziapostolou M, Polytarchou C, Aggelidou E, Drakaki A, Poultsides GA, Jaeger SA, Ogata H, Karin M, Struhl K, Hadzopoulou-Cladaras M, Iliopoulos D. An HNF4alpha-miRNA inflammatory feedback circuit regulates hepatocellular oncogenesis. Cell. 2011 Dec 9;147(6):1233-47. doi: 10.1016/j.cell.2011.10.043.
Piskounova E, Polytarchou C, Thornton JE, LaPierre RJ, Pothoulakis C, Hagan JP, Iliopoulos D, Gregory RI. Lin28A and Lin28B inhibit let-7 microRNA biogenesis by distinct mechanisms. Cell. 2011 Nov 23;147(5):1066-79. doi: 10.1016/j.cell.2011.10.039.
Iliopoulos D, Jaeger SA, Hirsch HA, Bulyk ML, Struhl K. STAT3 activation of miR-21 and miR-181b-1 via PTEN and CYLD are part of the epigenetic switch linking inflammation to cancer. Mol Cell. 2010 Aug 27;39(4):493-506. doi: 10.1016/j.molcel.2010.07.023.
Iliopoulos D, Lindahl-Allen M, Polytarchou C, Hirsch HA, Tsichlis PN, Struhl K. Loss of miR-200 inhibition of Suz12 leads to polycomb-mediated repression required for the formation and maintenance of cancer stem cells. Mol Cell. 2010 Sep 10;39(5):761-72. doi: 10.1016/j.molcel.2010.08.013.
Iliopoulos D, Hirsch HA, Struhl K. An epigenetic switch involving NF-kappaB, Lin28, Let-7 MicroRNA, and IL6 links inflammation to cell transformation. Cell. 2009 Nov 13;139(4):693-706. doi: 10.1016/j.cell.2009.10.014. Epub 2009 Oct 29.