Fabrizio Loreni
e-mail: loreni AT uniroma2.it
affiliation: Università di Roma Tor Vergata
research area(s): Molecular Biology, Cancer Biology
Course:
Cell and Molecular Biology
University/Istitution: Università di Roma Tor Vergata
University/Istitution: Università di Roma Tor Vergata
Education and Training
- 1986-88 Post-Doctoral fellow in the laboratory of Dr. Diane Robins at the Biology Department of Columbia University in New York.
Research: hormonal regulation of gene expression using as model system the Slp gene of mouse.
- 1985 Degree "Laurea" in Chemistry at the University of Rome La Sapienza.
Research and Professional Experience
- 2000-today Professore Associato of Molecular Biology at Dept of Biology of the University of Rome "Tor Vergata".
Research: cis and trans-acting elements involved in the translational control of TOP mRNAs. Molecular analysis of Blackfan-Diamond anemia. Role of PIM1 kinase and ribosomal stress in prostate cancer cells
- 1995-96 Visiting scientist for six months in the laboratory of Dr. George Thomas at the Friedrich Miescher Institute in Basel
Research: translational control in in vitro systems.
- 1989 Ricercatore of Molecular Biology at Dept of Biology of the University of Rome "Tor Vergata"
Research: transcriptional and translational regulation of ribosomal protein genes; analysis of cis- and trans-acting element involved in the translational control of TOP mRNAs
- 1986-88 Post-Doctoral fellow in the laboratory of Dr. Diane Robins at the Biology Department of Columbia University in New York.
Research: hormonal regulation of gene expression using as model system the Slp gene of mouse.
- 1985 Degree "Laurea" in Chemistry at the University of Rome La Sapienza.
Research and Professional Experience
- 2000-today Professore Associato of Molecular Biology at Dept of Biology of the University of Rome "Tor Vergata".
Research: cis and trans-acting elements involved in the translational control of TOP mRNAs. Molecular analysis of Blackfan-Diamond anemia. Role of PIM1 kinase and ribosomal stress in prostate cancer cells
- 1995-96 Visiting scientist for six months in the laboratory of Dr. George Thomas at the Friedrich Miescher Institute in Basel
Research: translational control in in vitro systems.
- 1989 Ricercatore of Molecular Biology at Dept of Biology of the University of Rome "Tor Vergata"
Research: transcriptional and translational regulation of ribosomal protein genes; analysis of cis- and trans-acting element involved in the translational control of TOP mRNAs
Alteration of ribosome biosynthesis in genetic diseases and prostate cancer
Our research is focused on the molecular mechanisms underlying the regulation of the synthesis, function and metabolism of the ribosome in vertebrate cells.
1) Diamond-Blackfan anemia (DBA) is the first human disease associated to mutations in ribosomal structural protein. In fact, ribosomal protein (RP) S19 is mutated in about 25% of patients, whereas another 10% show mutations in RPS24, RPS17, RPL35A, RPL11, and RPL5. The major clinical feature of DBA is a congenital erythroblastopenia but approximately 30% of affected children present a variety of associated physical anomalies.
It is not clear how alterations in the synthesis and/or function of a ribosomal protein could influence normal development. We study the signaling pathways involved in the response to ribosomal defect (e.g. AKT/mTOR pathway) and the mechanism of regulation in the synthesis of ribosomal components.
2) We also study the role of PIM1 kinase in prostate cancer cells focusing on its recently discovered structural and functional interaction with the ribosome. PIM1 is a constitutively active serine/threonine kinase regulated by cytokines, growth factors and hormones. It has been implicated in the control of cell cycle progression and apoptosis and its overexpression has been associated to various kinds of malignancies. In particular, PIM1 was found to be a prognostic marker for prostate cancer (PCa) and it has been suggested that PIM1 upregulation could be an early event in the development of prostate malignancy. We are now addressing the relationship between the function of PIM1 and its interaction with the ribosome and the role of PIM1 in response to alteration of the translational apparatus.
Our research is focused on the molecular mechanisms underlying the regulation of the synthesis, function and metabolism of the ribosome in vertebrate cells.
1) Diamond-Blackfan anemia (DBA) is the first human disease associated to mutations in ribosomal structural protein. In fact, ribosomal protein (RP) S19 is mutated in about 25% of patients, whereas another 10% show mutations in RPS24, RPS17, RPL35A, RPL11, and RPL5. The major clinical feature of DBA is a congenital erythroblastopenia but approximately 30% of affected children present a variety of associated physical anomalies.
It is not clear how alterations in the synthesis and/or function of a ribosomal protein could influence normal development. We study the signaling pathways involved in the response to ribosomal defect (e.g. AKT/mTOR pathway) and the mechanism of regulation in the synthesis of ribosomal components.
2) We also study the role of PIM1 kinase in prostate cancer cells focusing on its recently discovered structural and functional interaction with the ribosome. PIM1 is a constitutively active serine/threonine kinase regulated by cytokines, growth factors and hormones. It has been implicated in the control of cell cycle progression and apoptosis and its overexpression has been associated to various kinds of malignancies. In particular, PIM1 was found to be a prognostic marker for prostate cancer (PCa) and it has been suggested that PIM1 upregulation could be an early event in the development of prostate malignancy. We are now addressing the relationship between the function of PIM1 and its interaction with the ribosome and the role of PIM1 in response to alteration of the translational apparatus.
Selected publications 2006-2011
1. Iadevaia, V., Caldarola, S., Biondini, L., Gismondi, A., Karlsson, S., Dianzani, I., and Loreni, F. (2010) PIM1 kinase is destabilized by ribosomal stress causing inhibition of cell cycle progression. Oncogene 29:5490-9
2. Quarello P, Garelli E, Carando A, Brusco A, Calabrese R, Dufour C, Longoni D, Misuraca A, Vinti L, Aspesi A, Biondini L, Loreni F, Dianzani I, Ramenghi U (2010) Diamond-Blackfan anemia: genotype-phenotype correlation in Italian patients with RPL5 and RPL11 mutations. Haematologica 95:206-13
3. Caldarola, S., De Stefano, M.C., Amaldi, F., and Loreni, F. (2009). Synthesis and function of ribosomal proteins--fading models and new perspectives. FEBS J 276, 3199-3210
4. Dianzani I, Loreni F (2008) Diamond-Blackfan anemia: a ribosomal puzzle. Haematologica 93(11):1601-1604
5. Bianchini A, Loiarro M, Bielli P, Busà R, Paronetto MP, Loreni F, Geremia R, Sette C. (2008). Phosphorylation of eIF4E by MNKs supports protein synthesis, cell cycle progression and proliferation in prostate cancer cells. Carcinogenesis 29:2279-2288
6. Iadevaia V., Caldarola S., Tino E., Amaldi F. and Loreni F. (2008). All translation elongation factors and the e, f, and h subunits of translation initiation factor 3 are encoded by 5' terminal oligopyrimidine (TOP) mRNAs. RNA 14:1730-36
7. Campagnoli MF, Ramenghi U, Armiraglio M, Quarello P, Garelli E, Carando A, Avondo F, Pavesi E, Fribourg S, Gleizes PE, Loreni F, Dianzani I. (2008). RPS19 mutations in patients with Diamond-Blackfan anemia. Hum Mutat 29,911-20
8. Angelini M, Cannata S, Mercaldo V, Gibello L, Santoro C, Dianzani I and Loreni F. (2007). Missense mutations associated to Diamond-Blackfan Anemia affect ribosomal protein S19 assembly into ribosome. Hum Mol Genet. 16:1720-7
9. Orru, S., Aspesi, A., Armiraglio, M., Caterino, M., Loreni, F., Ruoppolo, M., Santoro, C. and Dianzani, I. (2007) Analysis of the ribosomal protein S19 interactome. Mol Cell Proteomics, 6, 382-393.
10. Provenzani A, Fronza R, Loreni F, Pascale A, Amadio M, Quattrone A. (2006). Global alterations in mRNA polysomal recruitment in a cell model of colorectal cancer progression to metastasis. Carcinogenesis 27:1323-33
1. Iadevaia, V., Caldarola, S., Biondini, L., Gismondi, A., Karlsson, S., Dianzani, I., and Loreni, F. (2010) PIM1 kinase is destabilized by ribosomal stress causing inhibition of cell cycle progression. Oncogene 29:5490-9
2. Quarello P, Garelli E, Carando A, Brusco A, Calabrese R, Dufour C, Longoni D, Misuraca A, Vinti L, Aspesi A, Biondini L, Loreni F, Dianzani I, Ramenghi U (2010) Diamond-Blackfan anemia: genotype-phenotype correlation in Italian patients with RPL5 and RPL11 mutations. Haematologica 95:206-13
3. Caldarola, S., De Stefano, M.C., Amaldi, F., and Loreni, F. (2009). Synthesis and function of ribosomal proteins--fading models and new perspectives. FEBS J 276, 3199-3210
4. Dianzani I, Loreni F (2008) Diamond-Blackfan anemia: a ribosomal puzzle. Haematologica 93(11):1601-1604
5. Bianchini A, Loiarro M, Bielli P, Busà R, Paronetto MP, Loreni F, Geremia R, Sette C. (2008). Phosphorylation of eIF4E by MNKs supports protein synthesis, cell cycle progression and proliferation in prostate cancer cells. Carcinogenesis 29:2279-2288
6. Iadevaia V., Caldarola S., Tino E., Amaldi F. and Loreni F. (2008). All translation elongation factors and the e, f, and h subunits of translation initiation factor 3 are encoded by 5' terminal oligopyrimidine (TOP) mRNAs. RNA 14:1730-36
7. Campagnoli MF, Ramenghi U, Armiraglio M, Quarello P, Garelli E, Carando A, Avondo F, Pavesi E, Fribourg S, Gleizes PE, Loreni F, Dianzani I. (2008). RPS19 mutations in patients with Diamond-Blackfan anemia. Hum Mutat 29,911-20
8. Angelini M, Cannata S, Mercaldo V, Gibello L, Santoro C, Dianzani I and Loreni F. (2007). Missense mutations associated to Diamond-Blackfan Anemia affect ribosomal protein S19 assembly into ribosome. Hum Mol Genet. 16:1720-7
9. Orru, S., Aspesi, A., Armiraglio, M., Caterino, M., Loreni, F., Ruoppolo, M., Santoro, C. and Dianzani, I. (2007) Analysis of the ribosomal protein S19 interactome. Mol Cell Proteomics, 6, 382-393.
10. Provenzani A, Fronza R, Loreni F, Pascale A, Amadio M, Quattrone A. (2006). Global alterations in mRNA polysomal recruitment in a cell model of colorectal cancer progression to metastasis. Carcinogenesis 27:1323-33
Project Title:
Project Title:
Role of PIM1 in ribosomal stress in prostate cancer cells
The aim of this project is to study the structural and functional interaction of PIM1 kinase with the ribosome and the role of this interaction in prostate cancer. PIM1 was found to be a prognostic marker for prostate cancer (PCa) and it has been suggested that PIM1 upregulation could be an early event in the development of prostate malignancy.
The project will follow two major objectives:
A) To study the relationship between the function of PIM1 and its interaction with the ribosome;
B) To address the role of PIM1 in response to alteration of the translational apparatus.
The project will follow two major objectives:
A) To study the relationship between the function of PIM1 and its interaction with the ribosome;
B) To address the role of PIM1 in response to alteration of the translational apparatus.
Project Title:
Role of mTORC2 complex in ribosomal stress
Mammalian target of rapamycin (mTOR) is a conserved serine/threonine kinase that regulates cell cycle progression, protein translation, metabolism, and cellular proliferation by means of regulation of ribosomal biogenesis and protein synthesis.
The project will follow two major objectives:
A) To study the relationship between the function of PIM1 and mTORC2 and their interaction with the ribosome
B) To address the role of mTORC2 in response to alteration of the translational apparatus
The project will follow two major objectives:
A) To study the relationship between the function of PIM1 and mTORC2 and their interaction with the ribosome
B) To address the role of mTORC2 in response to alteration of the translational apparatus