Guidalberto Manfioletti
Guidalberto Manfioletti
affiliation: Università di Trieste - Dip. di Scienze della Vita
research area(s): Cancer Biology
Course: Molecular Biomedicine
University/Istitution: Università di Trieste
Guidalberto Manfioletti was born in Trieste (Italy) on the 29th November 1959.
He got the Scientific Diploma (Higher education) on June 1978.
He graduated in Biological Sciences on July 1982 at the University of Trieste, first class honours, discussing an experimental thesis in cytogenetics.
From 1985 to 1986, he was a Research Associate at the Childrens Hospital in Trieste, in the Dept. of Human Genetic.
From 1986 to 1988 he received a fellowship from "Area per la Ricerca" - Trieste, and worked with prof. C.Schneider on the characterization of genes involved in the regulation of growth arrest, first at the European Molecular Biology Laboratories (EMBL-Heidelberg- Germany) and later at the International Centre for Genetic Engineering and Biotechnology (ICGEB-Trieste-Italy).
In 1988 he got the position of Researcher in Biochemistry at the Dept. of Biochemistry, Biophysics and Macromolecular Chemistry at the University of Trieste.
From 1988 he has been working at the Department of Biochemistry, Biophysics and Macromolecular Chemistry in collaboration with prof. V.Giancotti on the molecular characterization of High Mobility Group A (HMGA) proteins and continued the collaboration with prof. C. Schneider (Laboratorio Nazionale CIB "Area per la Ricerca-Trieste).
His research activity is focussed on HMGA proteins and homeobox factors.
He was Visiting Professor at the Biophysics Laboratories - University of Portsmouth -U.K. (1991) (prof. C. Crane-Robinson), and at the Institute of Cancer Research - Chester Beatty Laboratories -London - U.K (1995) (Dr. G.H. Goodwin).
Awarded of a fellowship from the Fondazione Italiana per la Ricerca sul Cancro he was visiting Professor at the Schepens Eye Research Institute-Harvard Medical School (Boston, USA) in the laboratory of dr. Santa J. Ono (1996 - 1997).
In 2001 he got the position of Associate Professor of Biochemistry at the University of Trieste.
At the Dep. of Life Sciences Prof. Manfioletti coordinates the HMGA research group.

From 1988 to 1991 he is lecturer, teaching in graduate courses of Biochemistry and Molecular Biology.
From 1991 to 2001 Assistant Professor of Molecular Biology, Faculty of Science, University of Trieste.
From 2001 Associate Professor of Biochemistry, Faculty of Science, University of Trieste, teaching courses of Biochemistry, Molecular biology and Applied biochemistry.
He is President of the "Laurea magistrale" in Functional genomics.
He is coordinator of the Double Diploma program between the Master degree in Functional genomics and the Master de Sciences Santé et Applications mention "Génétique" of the Universities of Paris Diderot-Paris 7 e Paris-Descartes-Paris 5.
Eukaryotic genes are contained within a higher order complex of DNA and histones called chromatin. Although packaging of DNA into chromatin provides the means for compaction of the entire genome to fit in the nucleus, it restricts the access to the many regulatory proteins required for the orderly progression of essential biological processes such as transcription, replication, repair and recombination. The chromatin, however, is not a static structure, but rather a dynamic assembly that condenses and decondenses in response to specific signals during cell life.

High-Mobility-Group (HMG) proteins are an abundant class of nuclear factors that play an important role in unfolding and remodelling the chromatin structure. HMG proteins are the most abundant group of non histone nuclear proteins, they are regarded as "architectural transcription factors" since they can interact with DNA and nuclear factors promoting the formation of high-order nuclear complexes that regulate many nuclear functions.

Presently, the primary focus of our laboratory is the study of a particular subgroup of HMG proteins (HMGA, or HMGI(Y) according to the old nomenclature) which are highly expressed during embryogenesis and in neoplastic cells but they expression is very low in adult somatic tissues.
Using a variety of biochemical, proteomic, cell biological and molecular biological approaches we study the structure of these proteins and of their genes, and in particular their function in the context of neoplastic transformation and apoptosis.
Sgarra R, Lee J, Tessari MA, Altamura S, Spolaore B, Giancotti V, Bedford MT, Manfioletti G. The AT-hook of the chromatin architectural transcription factor HMGA1a is arginine methylated by PRMT6. (2006) J. Biol. Chem. 281: 3764-3772.

Frasca F., A. Rustighi, R. Malaguarnera, S. Altamura, P. Vigneri, G. Del Sal, V. Giancotti, V. Pezzino, R. Vigneri, and G. Manfioletti. HMGA1 inhibits the function of p53 family members in thyroid cancer cells. (2006) Cancer Res. 66:2980-2989.

Puppin C, Puglisi F, Pellizzari L, Manfioletti G, Pestrin M, Pandolfi M, Piga A, Di Loreto C, Damante G. HEX expression and localization in normal mammary gland and breast carcinoma. (2006) BMC Cancer. 6:192

Thuault S, Valcourt U, Petersen M, Manfioletti G, Heldin CH, Moustakas A. Transforming growth factor-{beta} employs HMGA2 to elicit epithelial-mesenchymal transition. (2006) J. Cell. Biol. 174:175-183.

Benini F, Onorati M, Altamura S, Manfioletti G, and Vignali R. Identification and developmental expression of Xenopus hmga2beta. (2006) Biochem. Biophys. Res. Commun. 351:392-397.

Cattaruzzi G., Altamura S., Tessari MA., Rustighi A., Giancotti V., Pucillo C., and Manfioletti G. The second AT-hook of the architectural transcription factor HMGA2 is determinant for nuclear localization and function (2007) Nucl. Acids Res. 35:1751-1760.

Sgarra R., Furlan C., Zammitti S., Lo Sardo A., Maurizio E., Di Bernardo J., Giancotti V. and Manfioletti G. Interaction proteomics of the HMGA chromatin architectural factors. (2008) Proteomics 8:4721-4732.

Sgarra R., Maurizio E., Zammitti S., Lo Sardo A., Giancotti V., and Manfioletti G. Macroscopic differences in oncoproteins HMGA posttranslational modifications: C-terminal phosphorylation of HMGA2 affects its DNA binding properties. J. Prot. Res. 2009 Jun;8(6):2978-89.

Sgarra R, Zammitti S, Lo Sardo A, Maurizio E, Arnoldo L, Pegoraro S, Giancotti, V, Manfioletti G. HMGA molecular network: From transcriptional regulation to chromatin remodeling. Biochim Biophys Acta. 2010 Jan-Feb;1799(1-2):37-47. Epub 2009 Sep 2.

Malini E., Maurizio E., Bembich S., Sgarra R., Edomi P., Manfioletti G. HMGA Interactome: New Insights from Phage Display Technology. Biochemistry. 2011 May 3;50(17):3462-8. Epub 2011 Apr 11. PubMed PMID: 21417337.

Maurizio E., Cravello L., Brady L., Spolaore B., Arnoldo L., Giancotti V., Manfioletti G., Sgarra R. A conformational role for the C-terminal tail of the intrinsically disordered High Mobility Group A (HMGA) chromatin factors. J Proteome Res. 2011 May 6. [Epub ahead of print] PubMed PMID: 21545188.
Project Title:
HMGA proteins in breast cancer
The High Mobility Group A (HMGA1 and HMGA2) proteins constitute a family of
nuclear factors that play an important role in the execution of multiple biological processes in
eukaryotic cells. These architectural factors are able to assemble or modulate DNA/nucleoprotein
macromolecular complexes thus participating in gene expression regulation, chromatin remodelling and dynamics, replication, and DNA repair.
Being critical hubs in the chromatin network, they participate in a variety of biological processes such as embryogenesis, differentiation and neoplastic transformation.
HMGA expression is very high during embryogenesis whereas it is undetectable
or very low in differentiated somatic adult cells. HMGA overexpression is a constant
feature of human malignant neoplasms and in the last years the causal role of HMGA proteins in the
process of neoplastic transformation has been firmly established using both cellular and animal
models. We want to address the role played by HMGA1 in breast cancer progression.