Mario Notari

Graduate Research Prize Winners 2012

Mario

I was born in a city named Carpi in the heart of the province of Modena in the north of Italy. For as long as I can remember, I have always been interested in science.

I decided to become a molecular biologist because I’ve always been curious about understanding the principles that regulate life. One of my favorite quotes in science is from Albert Einstein: “learn from yesterday, live for today, hope for tomorrow. The important thing is to not stop questioning.”

My research career to date has primarily focused on the intracellular signaling pathways that are at the basis of cancer development. In 2002, during the final year of my medical biotechnology degree at the University of Modena and Reggio Emilia, in Italy, I joined the laboratory of Professor Bruno Calabretta at the Kimmel Cancer Center in Philadelphia, USA. Here I studied the effects of the BCR/ABL oncoprotein on the metabolism of RNA-binding proteins. I then joined Danilo Perrotti’s lab to complete the project, which resulted in the publication of my first-author paper on the study of the regulation of the ribonucleoprotein hnRNP K in the contest of Chronic Myelogenous Leukemia (CML). This achievement allowed me to gain a DPhil full-scholarship at the University of Oxford.

For the past four years, I have been reading for my postdoctoral degree at the Ludwig Institute for Cancer Research (LICR) under the supervision of Director Professor Xin Lu. During this time, I have developed skills in a wide variety of molecular and cellular techniques, and have gained further experience in in vivo procedures.

I have been investigating the functional and biological role in vivo of a protein called iASPP, using an inducible knock-out (KO) mouse as a model system. To further investigate iASPP’s functions in vivo, we generated a KO mouse in which iASPP is genetically silenced. We found that iASPP was highly expressed in both the heart and skin of the mouse. iASPP KO mice also showed severe dilated cardiomyopathy affecting the right ventricle of the organ, making them a novel in vivo model for the pre-clinical study of cardiovascular disease. Defects in hair growth and impaired epidermal stratification were also noted and investigated. A paper covering the latter was recently published into the Proceedings of National Academy (PNAS) journal, while the other is under peer-review in Nature Cell Biology.

My DPhil experience in Oxford was just amazing! It’s a wonderful place to live for its astonishing buildings and architecture, and the numerous pubs that drive Oxford social-life, but above all, everywhere you go you just breathe knowledge. I love the fact that Oxford University is a melting pot of different cultures, and that the exchange of ideas is emphasised.

Publications:

1. Notari M., Neviani P., Santhanam R., Galietta A, Chang JS., Blaser B.W., Willis A.E., Roy D.C., Caligiuri M.A., Marcucci G. and D. Perrotti. A MAPK/hnRNP K pathway controls BCR/ABL oncogenic potential by regulating c-myc mRNA translation. Blood. 2006 Mar 15;107(6):2507-16. Epub 2005 Nov 17.

2. Neviani P., Santhanam R., Notari M., Trotta R., Blaser B.W., Liu S., Mao H, Chang JS, Galietta A, Uttam A, Roy D.C., Valtieri M., Bruner-Klisovic R., Caligiuri M.A., Bloomfield C.D., Marcucci G., and D. Perrotti. The tumor suppressor PP2A is functionally inactivated in blast crisis CML through the inhibitory activity of the BCR/ABL-regulated SET protein. Cancer Cell.;8:355-68, 2005

3. Neviani P, Santhanam R, Oaks JJ, Eiring AM, Notari M, Blaser BW, Liu S, Trotta R, Muthusamy, N, Gambacorti-Passerini C, Druker BJ, Cortes J, Marcucci G, Chen CS, Verrills NM, Roy DC, Caligiuri MA, Bloomfield CD, Byrd JC, Perrotti D. FTY720, a new alternative for treating blast crisis chronic myelogenous leukemia acute lymphocytic and Philadelphia chromosome-positive leukemia. J Clin Invest. 2007 Sep;117(9):2408-21.

4. Eiring AM, Neviani P, Santhanam R, Oaks JJ, Chang JS, Notari M, Willis W, Gambacorti-Passerini C, Volinia S, Marcucci G, Caligiuri MA, Leone GW, Perrotti D. Identification of novel posttranscriptional targets of the BCR/ABL oncoprotein by ribonomics: requirement of E2F3 for BCR/ABL leukemogenesis. Blood. 2008 Jan 15;111(2):816-28. Epub 2007 Oct 9.

5. Notari M, Hu Y, Koch S, Lu M, Ratnayaka I, Zhong S, Baer C, Pagotto A, Salter V, Candi E, Melino G and Lu X. iASPP prevents cellular senescence and is required for normal epithelial stratification. PNAS 2011 Proc Natl Acad Sci U S A. 2011 Sep 19.

6. Notari M, Hu Y, Dupays L, Yavari A, Carr C, Zhong S, Ratnayaka I, Opel A, Tinker A, Clarke K, Watkins H, Mohun T and Lu X. iASPP: a novel regulator of desmosome that prevents cariocutaneous disorder. Nature Cell Biology. (submitted, under consideration 2012).