LAURA CASALINO
Moshe Yaniv laboratory
Unit of Gene Expression and Diseases, Department of Developmental Biology, Pasteur Institute, Paris

AP-1 Network Project

Curriculum Vitae

PERSONAL INFORMATION

Surname: Casalino
First Name: Laura

Place and date of birth: Verbania (VB), Italy 28 January, 1970
Nationality: Italian
Civil Status: unmarried

Titles awarded: Degree in Biological Sciences
Ph.D. in Biochemistry and Molecular Biology

Mother tongue: Italian

Other languages: English
French
Spanish


ACADEMIC TRAINING

Degree in Biological Sciences
Summa cum laude
12 July. 1994
University of Milan, Italy
Supervisor: Prof. Francesco Blasi,
Field of study: “Role of the transcription factors NF-?B and AP-1 on the transcriptional regulation of the human Urokinase gene”

Ph.D. on Biochemistry and Molecular Biology
22 March, 2001
“Federico II” University of Naples, Italy
Supervisor: Dr. Pasquale Verde, IGB-ABT, CNR of Naples, Italy
Field of study: “AP-1 transcription factor in oncogenic transformation of thyroid cells: role and regulation of Fra-1”


PROFESSIONAL EXPERIENCES

RESEARCH ACTIVITY

Supervisor: Prof. Francesco Blasi
Period: January 1993-March 1995
Place: Department of Genetics, University of Milan
Position: undergraduate/graduate student
Field of Study: Role of AP-1 and NF-kB transcription factors in the regulation of the human Urokinase gene by tumor promoters and cytochines in pulmonary carcinoma cells.

Supervisor: Dr. Pasquale Verde
Period: April 1995-June 2004
Place: Institute of Genetics and Biophysics “A. Buzzati-Traverso”
(IGB-ABT), CNR of Naples
Position: Fellow (1995-1996)
PhD student (1996-2000)
Post-doctoral fellow (2000-2004)
Field of Study: Mechanisms controlling positive (by IL-1?? and negative (by Glucocorticoid Receptor) regulation of the transcriptional enhancer of the human Urokinase gene.
Role of AP-1 and NF-?B transcription factors in neoplastic transformation of thyroid cells.
Role and regulation of Fra-1 in transformed thyroid cells.

Supervisor: Prof. Moshe Yaniv
Period: August-October 2001
September-December 2003
April-July 2004
December 2004 at present
Place: Unit of Gene Expression and Diseases, Department of Developmental Biology, Pasteur Institute, Paris
Field of Study: Role and regulation of Fra-1 in cell cycle control of thyroid cells.


PUBBLICATION LIST

Guerrini L., Casalino L., Corti A., Blasi F.
“NF-kB-mediated regulation of urokinase gene expression by PMA and TNF-? in human A549 cells”.
FEBS Letters 393: 69-73 (1996)

Visconti R., Cerutti J., Battista S., Fedele M., Trapasso F., Zeki K., Miano M.P., Casalino L., Curcio F., Santoro M., Fusco A.
“Expression of the neoplastic phenotype by human thyroid carcinoma cell lines requires NF-kB p65 protein expression”.
Oncogene 15(16): 1987-1994 (1997)

Vallone D., Battista S., Pierantoni G.M., Fedele M, Casalino L., Santoro M., Viglietto G., Fusco A., Verde P.
“Neoplastic transformation of rat thyroid cells requires the JunB and Fra-1 gene induction and the expression of the HMGI-C gene product”.
EMBO J. 16: 5310-5321 (1997)

Cirillo G. *, Casalino L. *, Vallone D., Caracciolo A., De Cesare D., Verde P.
“Role of distinct Mitogen-Activated Protein Kinase Pathways between Ets-2, ATF-2 and Jun-family members in human uPA gene induction by interleukin-1 and TPA”.
Molecular and Cellular Biology 19(9): 6240-6252 (1999)
* equally contributed to this work

Casalino L., De Cesare D., Verde P.
“Accumulation of Fra-1 in ras-transformed cells depends on both transcriptional autoregulation and MEK-dependent post-translational stabilization”.
Molecular and Cellular Biology 23(12): 4401-4415 (2003)


LIST OF AWARDED FELLOWSHIPS OR OTHER FUNDINGS

LONG TERM FELLOWSHIP
Italian Association for Cancer Research (A.I.R.C.) Fellowship
January 1995-December 1997

CNR fellowship
Laboratory of Dr. Pasquale Verde, IGB-ABT (CNR of Naples)
July - June 2004

SHORT-TERM FELLOWSHIP
FEBS Youth Travel Grant
August, 16-28, 1999

EMBO Short Term Fellowship
Laboratory of Prof. Moshe Yaniv, Pasteur Institute, Paris
August - October 2001

CNR/INSERM joint project: fellowship for short research stages in France
(September-December 2003)
Laboratory of Prof. Moshe Yaniv, Pasteur Institute, Paris

FEBS short Term Fellowship
(April-July 2004)
Laboratory of Prof. Moshe Yaniv (Unit of "Gene Expression and Disease", Department of Developmental Biology, Pasteur Institute, Paris)

AP-1 Network Project

Analysis of the role of Fra-1 in cell cycle regulation of thyroid cells
Mutational activation of Ras plays a major role in human tumorigenesis, and occurs at high frequency in several kinds of epithelial cancer. The study of Ras mutations in both benign and malignant follicular tumors indicates that K-ras is the most frequently altered gene in thyroid cancer, and that its activation is an early event in thyroid tumorigenesis. In vitro, follicular rat thyroid cells are fully transformed by the ras oncogene, which results in growth factor independence, morphological transformation and tumorigenicity in nude mice. The transformed phenotype is associated with the decrease or loss of differentiation. Thus, the rat thyroid cell lines represent an optimal model system for studying the epithelial tumorigenesis and the relationship between transformation and differentiation.
The dimeric composition of the transcription factor AP-1 is drastically modified by Ras-transformation in rat thyroid cells, where Fra-1 has been identified as the major AP-1 component. Furthermore the high expression of Fra-1 is essential in vitro for the maintenance of the transformed phenotype and increased Fra-1 levels have been observed in human thyroid tumors.
In K-ras-transformed thyroid cells the high expression of Fra-1 largely depends on Raf/MEK-dependent cascade and is mediated by a positive feedback mechanism, requiring both transcriptional auto-regulation and post-translational stabilization.
Recently, by combining Western blot and FACS analysis on asynchronous/synchronized cell cultures, we found that Fra-1 expression and modification are regulated during the cell cycle progression of K-ras transformed thyroid cells. In fact, in synchronized transformed cells the expression Fra-1 increases during the S-phase reaching the maximum level at the G2/M transition, while the content of Fra-1 rapidly decreases as cells enter the G1 phase. Furthermore, the electrophoretic mobility of Fra-1 in M phase appeared rather reduced, suggesting that a specific modification (perhaps phosphorylation) could occur.
Therefore we raised the question if Fra-1 in turns could regulate the cell cycle progression of thyroid cells. Accordingly this research proposal is aimed at understanding the following points:
Role of Fra-1 in the regulation of proliferation and cell cycle progression of thyroid cells
To investigate the functional role of Fra-1 as cell cycle regulator in thyroid epithelial cells, we are contemporarily performing a loss-of function approach a as well as gain-of function to investigate the role of Fra-1 over-expression in K-ras-transformed cells and the effects of its ectopic expression on growth properties of normal thyroid cells. To that we are currently analyzing the proliferation rate and the cell cycle profile of FRTL-5K-Ras-derived cell clones expressing a siRNA vector for stable down-regulation of Fra-1 and of a pool of stable clones expressing Fra-1 fused to the FLAG epitope.
Identification of Fra-1 target promoters involved in cell cycle control
A fundamental link between the AP-1 function and cell cycle has been established by analyzing the effect of the Jun-family members on the transcription of cyclins and cdk inhibitors.
Although the interaction of the Jun proteins with their target promoters likely requires the dimerization with Fos-family members, poor is known on the specific role of distinct Fos-related proteins in mediating the interaction with the promoter elements relevant for cell cycle control. Therefore, for the molecular characterization of the interaction between Fra-1 and cell cycle, we will perform a systematic analysis of the expression of different cyclins and inhibitors, in the cell clones stably over expressing Fra-1 and in transformed cells carrying the inactivation of Fra-1. The identification of candidate target genes will allow the elucidation of distinctive roles played by Fra-1 in cell cycle control.