Telephone: +39 0706758345-8346
Fax: +39 070666062
Personal webpage: here
Principal areas of expertise: Molecular pathology; Oncology
♦ Epigenetic/genetic changes associated to cancer development and progression
How and why cells are able to progress to cancer is a rather complex process requiring a series of epigenetic and genetic changes. A better knowledge of these changes is critical for understanding how to design new and more specific drugs for cancer therapy. Our laboratory has a long-standing interest in addressing and understanding signaling events that play an important role in tumorigenesis and metastasis. Therefore, we are defining the cascade of molecular events involved in the development of hepatocellular carcinoma using in vivo and in vitro model systems. Specifically, our studies focused on the identification, through Next Gen-Sequencing, genes and microRNA dysregulated in preneoplastic and neoplastic lesions generated by different experimental models of hepatocarcinogenesis. Metabolic reprogramming (switch from OXPHOS to Warburg phenotype) is also a research area currently investigated. The final goal of the undergoing research activities is to identify in animal models genes and/or microRNAs dysregulated at very early stages of the carcinogenic process and to translate the results to the human situation. In this project, the student will develop skills in various techniques of molecular biology, immunohistochemistry and histology. Moreover, she/he will also learn how to use the laser for microdissection and how to perform NGS and bioinformatic analysis.
Within this general line of research, specific projects are:
- Role of microRNA in normal and preneoplastic/neoplastic cell proliferation
- Role of autophagy in normal, preneoplastic and neoplastic cells
- Study of the anticancer activity of analogues of thyroid hormone
- Transcriptomic and miRNOmic analysis in liver carcinogenesis and other solid tumors
- Identification of gene mutations occurring at early stages of the multistep process of hepatocarcinogenesis
- Study of the mechanisms underlying the metabolic rewiring of preneoplastic lesions towards a Warburg phenotype
- Orrù C, Szydlowska M, Taguchi K, Zavattari P, Perra A, Yamamoto M, Columbano. A. Genetic inactivation of Nrf2 prevents clonal expansion of initiated cells in a nutritional model of rat hepatocarcinogenesis. J Hepatol. 2018 69:635-6432.
- Kowalik MA, Columbano A, Perra A. Thyroid Hormones, Thyromimetics and Their Metabolites in the Treatment of Liver disease. Front Endocrinol 2018;9:382.
- Mattu S, Saliba C, Sulas P, Zavattari P, Perra A, Kowalik MA, Monga SP, Columbano A High Frequency of β-Catenin Mutations in Mouse Hepatocellular Carcinomas Induced by a Nongenotoxic Constitutive Androstane Receptor Agonist. Am J Pathol. 2018 188:2497-2507
- Sulas P, Di Tommaso L, Novello C, Rizzo F, Rinaldi A, Weisz A, Columbano A, Roncalli M. A Large Set of miRNAs Is Dysregulated from the Earliest Steps of Human Hepatocellular Carcinoma Development. Am J Pathol. 2018; 188:785-794.
- Kowalik MA, Columbano A, Perra A. Emerging Role of the Pentose Phosphate. Pathway in Hepatocellular Carcinoma. Front Oncol. 2017;7:87.
- Perra A, Plateroti M, Columbano A. T3/TRs axis in hepatocellular carcinoma: new concepts for an old pair. Endocrine-Related Cancer 2016;23: R353-69.
- 7. Menegon S, Columbano A, Giordano S. NRF2, a Janus molecule in cancer. Trends Mol Med 2016;7:578-93..
- Frau C, Loi R, Petrelli A, Perra A, Menegon S, Kowalik MA, Pinna S, Leoni VP, Fornari F, Gramantieri L, Ledda-Columbano GM, Giordano S, Columbano A Local hypothyroidism favours the progression of rat preneoplastic lesions to HCC. Hepatology 2015;61: 249-259
- Zavattari P, Perra A, Menegon S, Kowalik MA, Petrelli A, Angioni MM, Follenzi A, Quagliata L, Ledda-Columbano GM, Terracciano L, Giordano S, Columbano A Nrf2, but not β-catenin, mutation represents an early event in rat hepatocarcinogenesis. Hepatology 2015; 62: 851-862
- Petrelli A, Perra A, Cora D, Sulas P, Menegon S, Manca C, Migliore C, Kowalik MA, Ledda-Columbano GM, Giordano S, Columbano A (2014) MicroRNA/gene profiling unveils early molecular changes and nuclear factor erythroid related factor 2 (NRF2) activation in a rat model recapitulating human hepatocellular carcinoma (HCC). Hepatology 59: 228-241