Mario Pende PhD Biochemistry

Course and current status

Education:                                           

1991      Diploma in Pharmaceutical Science, University of Genova,  Italy

1993      Diploma in Pharmacology, University of Genova, Italy.

2000      PhD degree, Biochemistry, Summa cum laude, University of  Basel, Switzerland

Professional experience:

1989-1992  Internship, Inst. Of  Pharmacology, University of Genova, Italy

1992-1993  Visiting Scientist, Mario Negri Institute, Milano, Italy

1993-1996  Visiting Scientist, NICHD, NIH, Bethesda, Maryland

1996-2000  PhD student, Friedrich Miescher Inst., Basel, Switzerland. Laboratory: Dr. G. Thomas

2000-2001  Post-doctoral Scientist, Friedrich Miescher Inst., Basel, Switzerland. Laboratory: Dr. G. Thomas

2002           Research Director, Avenir Program, INSERM U584, Paris, France.

2003           Permanent position (CR1 level) INSERM U584, Paris, France.

2007           Permanent position (DR2 level) INSERM U845, Paris, France

Invited Seminars: (last two years)

“Cell size and shape” Meeting, Les Treilles; “European Cancer Conference”, Paris; “Club Hématopoiese et oncogenèse” Meeting, Giens; “Regulation and therapeutic potential of the PI-3 kinase signaling pathway” Meeting, La Ciotat;  “Congrès de la Societé Francaise d’Hematologie”, Paris; “E. Gutmann Heritage-PaduaMuscleDays”, Padova; “Imaging signal transduction, proliferation and apoptosis” Summer School, Prague.

“4^th Cardiomet Symposium on the metabolic syndrome”, Lausanne; “Cell growth and the TOR pathway” Meeting, Les Treilles; “Cell growth, Metabolism and Cancer” Meeting, Glasgow; “9^th International Congress on Cell Biology”, Seoul; “Insulin-like growth factors in physiology and disease”, Gordon Conference, Ventura. “Pancreatic diseases: from molecules to patients”, Abruzzo Symposia, Fara San Martino; “11^th International Congress on amino acids, peptides and proteins”, Vienna; CNIO meeting “Energy of Cancer”, Madrid; “First ERC recipients Interdisciplinary Symposium”, Jerusalem; “1^st International Congress of Translational Research in Human Nutrition”, Clermont-Ferrand; “TSC scientific day”, Paris; “TOR, caloric restriction and anabolism in ageing”, Split; “Cancer metabolism”, Barcelona; “mTOR signalling in health and disease”, London; “Workshop sur les tumeurs et les malformations vasculaires de l’enfant”, Paris.

Awards:

2006      - Morgagni Prize for Studies on Metabolism, sponsored by Servier;

- Schlumberger Foundation Award.

- Fondation Recherche Medicale award.

2008      - European Research Council Award

Membership of Editorial Board:

- Skeletal Muscle

Scientific summary

Mammalian growth and metabolism are controlled by extracellular signals, such as insulin and insulin-like growth factors (IGFs). Depending on nutrient availability, these factors regulate the size and number of cells and the synthesis of lipids, proteins and sugars.

The aim of the research program is to determine if these responses are coordinated or if they are relayed by intracellular signaling pathways independent.

Target Of Rapamycin (TOR) is an evolutionary conserved protein kinase that plays a central role in the integration of growth factor and nutrient signals. The overall goal of the lab is:

-    to identify the mTOR targets involved in cell growth, proliferation and metabolic control

-    to evaluate the impact of mTOR deregulation on human patients and mouse models of disease, with special focus on cancer, type 2 diabetes, myopathy and obesity.

Mammalian Target Of Rapamycin (mTOR) exists in the cell in two distinct protein complexes with different partners. mTOR complex 1 and 2 respectively phosphorylate two AGC kinase family members, S6 kinases and Akt. These complexes have differential sensitivity to nutrients, which activate the S6K pathway but down-regulate Akt signalling. Our group uses mouse mutants in these genes to address the coordination between these signalling elements.

Mammalian cells require two extracellular signals for anabolism: the growth factor peptides such as insulin and insulin-like growth factors, and the nutrients, such as glucose and amino acids. The interplay between growth factors and nutrients is essential for eukaryotic cells. Insulin stimulates nutrient uptake and storage. Nutrients are required for growth factor stimulated growth and proliferation. However excess of nutrients are also known to inhibit several metabolic actions of growth factors and cause insulin resistance.

The scientific questions our group is addressing are the following:

1)      What are the molecular mechanisms by which S6 kinases regulate cell size

2)      How do mTOR complexes and substrates favour cancer progression?

3)      How does mTOR regulate ribosome biogenesis?

4)      What is the crosstalk between Akt and S6K branches of mTOR signalling in the regulation of nutrient homeostasis? Are defects in these kinase activities leading to type 2 diabetes?

5)      What is the relationship between autophagy, cell growth and cancer development?

6)      Are mutations in the mTOR pathway linked to human myopathies?