Mariastella Zannini
Mariastella Zannini
affiliation: CNR-Institute of Experimental Endocrinology and Oncology (IEOS)
research area(s): Molecular Biology, Cancer Biology
Course: Genetics and Molecular Medicine
University/Istitution: Università di Napoli Federico II
Mariastella Zannini has got a degree in Biological Sciences from the University of Naples Federico II. She started her scientific activity in 1985 as a student at the Department of Biochemistry of the Medical School at the University of Naples Federico II. Later on, in 1987, she went to the National Institutes of Health (Bethesda, USA) in the laboratory of Dr. S.A. Aaronson, where she remained until 1990, first as Guest Researcher and subsequently as Visiting Fellow. In 1990, she left the National Institute of Health and moved to the European Molecular Biology Laboratory (Heidelberg, Germany), in the group of Prof. R. Di Lauro. In this occasion, she started to study the molecular mechanisms regulating thyroid cell differentiation. Since than, her interests have been focused on the thyroid, and specifically on the regulation of thyroid-specific gene expression. In 1992, she moved from the EMBL to the Stazione Zoologica A. Dohrn (Naples, Italy), supported first by an AIRC fellowship and subsequently by a temporary position as Researcher. In 1997, she obtained a permanent position at the University of Naples Federico II, where she continued her studies. In 2001 she became Research Fellow in Medical Genetics at the University of Naples Federico II, and in January 2002 she became Research Associate of the CNR.
PAX (PAired boX) genes comprise a small but developmentally crucial gene family that encodes a set of transcription factors. PAX proteins play an essential role in organogenesis during embryonic development in regulating cell proliferation and self-renewal, resistance to apoptosis, migration of embryonic precursor cells, and the coordination of specific differentiation programs.
Since many years, our laboratory has been studying thoroughly PAX8 that is expressed in adult kidney and thyroid. In particular, during thyroid development Pax8 is expressed upon transition from undifferentiated endoderm cells to thyroid follicular fated cells in the thyroid anlage and continues to be expressed throughout development and in the adult. Our group demonstrated that PAX8 is necessary for the expression of thyroid-specific genes, including thyroglobulin (Tg), thyroperoxidase (TPO) and sodium/iodide symporter (NIS) essential for the synthesis of active thyroid hormone. However, still little is known about Pax8 target genes or the specific developmental processes in which this transcription factor plays a role. One main goal of our studies is to elucidate the orchestrated role of Pax8 and its target genes in thyroid differentiation through the knock-down of Pax8 expression in differentiated thyroid cell, followed by genomewide microarray analysis and detailed characterization of the biological role in differentiation, proliferation and survival of thyroid cells of the identified target genes.
The normal function of PAX proteins may be subverted during the progression of a number of specific malignancies. This is supported by the fact that expression of PAX proteins is dysregulated in several different types of tumors, in particular they have been found over-expressed and selectively mutated by activating translocations in specific cancers. Intriguingly, in many cancer cell lines the presence or absence of PAX gene expression did not necessarily match the type of fetal or adult tissue in which PAX genes are normally expressed. Although the constitutive expression of PAX genes in adult tissues may not in itself be oncogenic, the observation that a very high proportion of tumors expresses PAX genes irrespective of their tissue of origin suggests that PAX gene expression confers a strong advantage to cancer cell growth. Interestingly, aberrant transcriptional expression of PAX8 has been reported in epithelial ovarian cancer, and it was reported as one of the top 40 genes that was specifically upregulated in different types of ovarian carcinoma. Nevertheless, to date there aren't studies that try to define how PAX8 expression may be contributing to the development and/or progression of ovarian cancer.
Our more than ten years of experience on PAX8 studies and the availability in our laboratory of many reagents and expertise necessary to study this transcription factor prompt us to pioneer the molecular characterization of this master regulatory gene in ovarian cancer development. We believe that a full understanding of Pax8 function and the identification of its target genes in the ovary represent a very important goal for a better knowledge of the physiological and the pathological role of this transcription factor. We are currently working on this aspect very actively.
de Cristofaro T., Di Palma T., Ferraro A., Corrado A., Lucci V., Franco R., Fusco A., Zannini M. (2011) TAZ/WWTR1 is overexpressed in papillary thyroid carcinoma. (Eur. J. Cancer, vol. 47, pp. 926-933).

Di Palma T., Zampella E., Filippone M.G., Macchia P.E., Ris-Stalpers C., de Vroede M., Zannini M. (2010) Characterization of a novel loss of function mutation of PAX8 associated with congenital hypothyroidism. (Clin Endocrinol, vol. 73, pp. 808-814).

Nitsch R., Di Dato V., di Gennaro A., de Cristofaro T., Abbondante S., De Felice M., Zannini M., Di Lauro R. (2010) Comparative genomics reveals a functional thyroid-specific element in the far upstream region of the PAX8 gene. (BMC Genomics, vol. 11, pp. 306).

Ferrara A.M., De Sanctis L., Rossi G., Capuano S., Del Prete G., Zampella E., Gianino P., Corrias A., Fenzi G., Zannini M., Macchia P.E. (2009) Mutations in TAZ/WWTR1, a co-activator of NKX2.1 and PAX8 are not a frequent cause of thyroid dysgenesis. (J Endocrinol Invest, vol. 32, pp. 238-241).

Rivas M., Mellström B., Torres B., Cali G., Ferrara A.M., Terracciano D., Zannini M., Morreale de Escobar G., Naranjo J.R. (2009) The DREAM protein is associated to thyroid enlargement and nodular development. (Mol Endocrinol, vol. 23, pp. 862-870).

de Cristofaro T., Mascia A., Pappalardo A., D'Andrea B., Nitsch L., Zannini M. (2009) Pax8 protein stability is controlled by sumoylation (J Mol Endocrinol, vol. 42, pp. 35-46).

Di Palma T., D'Andrea B., Liguori G.L., Liguoro A., de Cristofaro T., Del Prete D., Pappalardo A., Mascia A., Zannini M. (2009) TAZ is a coactivator for Pax8 and TTF-1, two transcription factors involved in thyroid differentiation (Exp. Cell Res., vol. 315, pp. 162-175).

Di Palma T., de Cristofaro T., D'Ambrosio C., Del Prete D., Scaloni A., Zannini M. (2008) Poly(ADP-ribose) polymerase-1 binds to Pax8 and inhibits its transcriptional activity. (J Mol Endocrinol, vol. 41, pp. 379-388).

D'Andrea B., Iacone R., Di Palma T., Nitsch R., Baratta M.G., Nitsch L., Di Lauro R., Zannini M. (2006) Functional inactivation of the transcription factor Pax8 through oligomerization chain reaction. (Mol Endocrinol, vol. 20, pp. 1810-1824).
Project Title:
Molecular characterization of the transcription factor PAX8 in ovarian cancer development.