Deptartment of Microbiology and Immunobiology
Department of Cancer Immunology & AIDS
Dana Farber Cancer Institute
450 Brookline Ave.
Smith Building, Room 770A
Boston, MA 02215
Division of Immunology
Our laboratory is interested to study the inter-complexity between chronic inflammatory diseases, such as ulcerative colitis, obesity and cancer, identify 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 our research is to identify how extracellular and intracellular inflammatory stimuli contribute to the transformation of normal cells into cancer cells. In particular, we strive to understand how perturbations of the tumor microenvironment contribute to oncogenic transformation and potentially formation and maintenance of cancer stem cell populations. Furthermore, we are 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. In our laboratory we are 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.
Iliopoulos D, Hirsch HA, Struhl K. Metformin decreases the dose of chemotherapy for prolonging tumor remission in mouse xenografts involving multiple cancer types. Cancer Res, 71:3196-201, 2011.
Stagakis E, Bertsias G, Verginis P, Nakou M, Hatziapostolou M, Kritikos H, Iliopoulos D, Boumpas DT. Identification of novel microRNA signatures linked to human lupus disease activity and pathogenesis: miR-21 regulates aberrant T cell responses through regulation of PDCD4 expression. Ann Rheum Dis. 70:1496-506, 2011.
Nakou M, Bertsias G, Stagakis I, Centola M, Tassiulas I, Hatziapostolou M, Kritikos I, Goulielmos G, Boumpas DT, Iliopoulos D. Gene Network Analysis of Bone Marrow Mononuclear Cells Reveals Activation of Multiple Kinase Pathways in Human Systemic Lupus Erythematosus. PLoS One, 5:e13351, 2010.
Hirsch HA*, Iliopoulos D*, Joshi A*, Zhang Y, Jaeger SA, Bulyk M, Liu SX, Struhl K. A transcriptional signature and common gene networks link cancer with lipid metabolism and diverse human diseases. Cancer Cell, 2010; 17:348-61. *equal contribution
Iliopoulos D, Hirsch HA, Struhl K. An epigenetic switch involving NF-κB, Lin28, let-7 microRNA, and IL6 links inflammation to cell transformation. Cell, 2009; 139:693-706.