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Caterina Missero

Professor of Molecular Biology


1989

Laurea cum Laude in Biology, University of Trieste, Italy

1989-1992

Postdoctoral Fellow at the Department of Pathology, School of Medicine, Yale University, New Haven, CT, USA.

1992-1993

Research Scientist at the Department of Pathology, School of Medicine, Yale University, New Haven, CT, USA.

1993-1996

Research Scientist at the Cutaneous Biology Research Center (CBRC), Department of Dermatology, Mass. Gen. Hospital, Charlestown, MA, USA.

1993-1996

Instructor in Dermatology at the Harvard Medical School, Boston, MA, USA.

1996-2000

Research Scientist in Biochemistry and Molecular Biology, Stazione ZoologicaA.Dohrn”, Naples, Italy.

2000-2006

Group Leader at the Telethon Institute of Genetics and Medicine (TIGEM), Naples, Italy.

2006-to present

Group Leader at the Centre for Genetic Engineering (CEINGE), Naples, Italy.

2014-12/2016

Associate Professor of Molecular Biology, Department of Biology, University of Naples Federico II, Naples, Italy.

12/2016-to present

Professor of Molecular Biology, Department of Biology, University of Naples Federico II, Naples, Italy.


Biography

After obtaining her degree in Biology at the University of Trieste (Italy) in 1989, Dr. Missero moved to Yale University (USA) as a post-doctoral fellow in the laboratory of Dr. Gian Paolo Dotto, where she became interested in skin biology and squamous cell carcinoma. Her earliest work was focused on assessing the validity of the oncogene cooperation model in multistep carcinogenesis, using the mouse skin as a model. After a post-doctoral training, she moved to Harvard Medical School where she was appointed Research Scientist and Instructor in Dermatology. At that time, she investigate the mechanisms coupling keratinocyte differentiation and cell cycle arrest.

On her return to Italy in 1996, her interest focused on the regulation of gene expression in thyroid cells. In 2000, she joined the Telethon Institute of Genetics and Medicine (TIGEM – Naples) as a Principal Investigator and devoted her time to study the transcriptional regulation in skin development under physiological and pathological conditions, mostly focusing on studying the function of the master regulator p63. More recently, her laboratory has been working constitutively and conditional mouse model for the studying of AEC syndrome, a complex disorder causing skin erosions. She is currently an independent investigator at the Centre for Genetic Engineering (CEINGE; www.ceinge.unina.it), and Professor in the Department of Biology at the Federico II University in Napoli, Italy.

At present she serves as Editorial Board Member of Experimental Dermatology and Associate Editor of Journal Investigative Dermatology. She is also Board Member of the Italian Society of Biophysics and Molecular Biology (SIBBM), and Board Member of the European Society of Dermatological Research (ESDR).

She is currently an independent investigator at the Centre for Genetic Engineering (CEINGE; www.ceinge.unina.it), and  Professor of Molecular Biology in the Department of Biology, Federico II University in Napoli, Italy.

 

Description of Research Expertise

1. Gene expression and transcription regulation in the epidermis and in the hair follicle

2. Keratinocyte proliferation and differentiation

3. Murine models of human diseases

4. Skin cancer: squamous cell carcinoma and basal cell carcinoma

 

Research interests

Currently Dr. Missero’s research is focused on the transcriptional mechanisms and genetic pathways required for normal skin development and function altered in inherited and acquired skin diseases. Using human and mouse primary keratinocytes and mouse genetic models, Dr. Missero is investigating how epithelial cells in the skin establish unique programs of gene expression. High throughput genomic analyses, cell biology, and functional approaches including CRIPSR/CAS9 gene deletion are used to unravel the molecular pathways that are crucial for the normal balance between stem cell maintenance and differentiation in the skin.

More specifically, her team is primarily dissecting the molecular pathways controlled by the transcription factor p63 in epidermal cells. p63 is responsible for the initiation of an epithelial stratification program during development, for maintenance of the proliferative potential of epidermal stem cells, and for cell adhesion. Mutations in the p63 gene have been shown to cause inherited disorders characterized by ectodermal dysplasia and cleft lip and/or palate. Conversely, the p63 gene is amplified and/or overexpressed in squamous cell carcinomas.

The main current research lines are:

1) Molecular alterations underlying the cutaneous defects in AEC syndrome. To study the pathogenetic mechanisms of this disorder, the laboratory has recently generated unique constitutive and conditional knock-in mouse models that faithfully recapitulates the AEC syndrome, as well as a knock-out mouse which specific lacks the p63 alpha isoform. Recently the laboratory has developed two mouse models for Ankyloblepharon-Ectodermal defects-Cleft lip/palate (AEC) syndrome, a genetic disorder caused by p63 mutations leading to severe skin erosions in infancy. These mouse models are currently under use to study the pathogenetic mechanisms of the disease. During these studies the group has revealed a novel function of p63 in controlling directly FGF signalling by transcriptional activation of FGFR2 and FGFR3 genes, thereby ensuring expansion of epidermal progenitor cells during embryonic development. Impaired p63 activity in AEC syndrome and lower FGF signalling are causative of a reduction in cell proliferation during embryonic development with a consequent reduction in size of the epidermal stem cell pool and skin hypoplasia.

2) Signalling pathways downstream of p63 and p73 in cutaneous squamous cell carcinoma (SCC). p53 mutations occur early and are a very frequent event in SCC pathogenesis, whereas the function of the p53 family members p63 and p73 is less well understood. Dr. Missero’s team is dissecting the molecular pathways downstream of p63 and its family member p73 in human SCCs. Although they have several target genes in common, p63 and p73 promote cell growth through only partially overlapping molecular mechanisms.

3) The Sonic hedgehog (SHH) pathway in basal cell carcinoma (BCC). The Shh pathway is constitutively active in several human tumors including BCC, the most common human malignancy. Using complex mouse genetics, the team is focused at investigating the putative function in tumorigenesis of downstream SHH target genes including the transcription factor FOXE1, which is highly expressed in BCC as compared to SCC and normal skin. Furthermore the group is contributing at understanding the function of thyroid hormone metabolism in BCC formation.

Selected publications since 2006

Antonini D, Mollo MR, Missero C. Research Techniques Made Simple: Identification and Characterization of Long Non-coding RNA in Dermatological Research. J Invest Dermatol. 2017 in press.

Missero C. The genetic evolution of skin squamous cell carcinoma: tumor suppressor identity matters. Exp Dermatol. 2016 May 19.

Di Girolamo D, Ambrosio R, De Stefano MA, Mancino G, Porcelli T, Luongo C, Di  Cicco E, Scalia G, Vecchio LD, Colao A, Dlugosz AA, Missero C, Salvatore D, Dentice M. Reciprocal interplay between thyroid hormone and microRNA-21 regulates hedgehog pathway-driven skin tumorigenesis. J Clin Invest. 2016 May 9.

Mollo MR, Antonini D, Cirillo L, Missero C. Research Techniques Made Simple: Skin Carcinogenesis Models: Xenotransplantation Techniques. J Invest Dermatol. 2016 Feb;136(2):e13-7.

Ferone G, Mollo MR, Missero C. Epidermal cell junctions and their regulation by p63 in health and disease. Cell Tissue Res. 2015 Jun;360(3):513-28.

Antonini D, Sirico A, Aberdam E, Ambrosio R, Campanile C, Fagoonee S, Altruda  F, Aberdam D, Brissette JL, Missero C. A composite enhancer regulates p63 gene expression in epidermal morphogenesis and in keratinocyte differentiation by multiple mechanisms. Nucleic Acids Res. 2015 Jan;43(2):862-74.

Mollo MR, Antonini D, Mitchell K, Fortugno P, Costanzo A, Dixon J, Brancati F, Missero C. p63-dependent and independent mechanisms of nectin-1 and nectin-4 regulation in the epidermis. Exp Dermatol. 2015 Feb;24(2):114-9.

Missero C, Antonini D. Crosstalk among p53 family members in cutaneous carcinoma. Exp Dermatol. 2014 Mar;23(3):143-6. Review.

Günschmann C, Stachelscheid H, Akyüz MD, Schmitz A, Missero C, Brüning JC,Niessen CM. Insulin/IGF-1 controls epidermal morphogenesis via regulation of FoxO-mediated p63 inhibition. Dev Cell. 2013 Jul 29;26(2):176-87.

Ferone G, Mollo MR, Thomason HA, Antonini D, Zhou H, Ambrosio R, De Rosa L,Salvatore D, Getsios S, van Bokhoven H, Dixon J, Missero C. p63 control of desmosome gene expression and adhesion is compromised in AEC syndrome. Hum Mol Genet. 2013 Feb 1;22(3):531-43.

Ferone G, Thomason HA, Antonini D, De Rosa L, Hu B, Gemei M, Zhou H, Ambrosio R, Rice DP, Acampora D, van Bokhoven H, Del Vecchio L, Koster MI, Tadini G, Spencer-Dene B, Dixon M, Dixon J, Missero C. Mutant p63 causes defective expansion of ectodermal progenitor cells and impaired FGF signalling in AEC syndrome. EMBO Mol Med. 2012 Mar;4(3):192-205.

Mitchell K, O'Sullivan J, Missero C, Blair E, Richardson R, Anderson B, Antonini D, Murray JC, Shanske AL, Schutte BC, Romano RA, Sinha S, Bhaskar SS, Black GC, Dixon J, Dixon MJ. Exome sequence identifies RIPK4 as the Bartsocas-Papas syndrome locus. Am J Hum Genet. 2012 Jan 13;90(1):69-75.

Fessing MY, Mardaryev AN, Gdula MR, Sharov AA, Sharova TY, Rapisarda V, Gordon KB, Smorodchenko AD, Poterlowicz K, Ferone G, Kohwi Y, Missero C, Kohwi-Shigematsu T, Botchkarev VA. p63 regulates Satb1 to control tissue-specific chromatin remodeling during development of the epidermis. J Cell Biol. 2011 Sep 19;194(6):825-39.

Rouleau M, Medawar A, Hamon L, Shivtiel S, Wolchinsky Z, Zhou H, De Rosa L, Candi E, de la Forest Divonne S, Mikkola ML, van Bokhoven H, Missero C, Melino G, Pucéat M, Aberdam D. TAp63 is important for cardiac differentiation of embryonic  stem cells and heart development. Stem Cells. 2011 Nov;29(11):1672-83.

Antonini D, Russo MT, De Rosa L, Gorrese M, Del Vecchio L, Missero C. Transcriptional repression of miR-34 family contributes to p63-mediated cell cycle progression in epidermal cells. J Invest Dermatol. 2010 May;130(5):1249-57.

Della Gatta G, Bansal M, Ambesi-Impiombato A, Antonini D, Missero C, di Bernardo D. Direct targets of the TRP63 transcription factor revealed by a combination of gene expression profiling and reverse engineering. Genome Res. 2008 Jun;18(6):939-48.

Antonini D, Dentice M, Mahtani P, De Rosa L, Della Gatta G, Mandinova A, Salvatore D, Stupka E, Missero C. Tprg, a gene predominantly expressed in skin, is a direct target of the transcription factor p63. J Invest Dermatol. 2008 Jul;128(7):1676-85.

Dentice M, Luongo C, Huang S, Ambrosio R, Elefante A, Mirebeau-Prunier D, Zavacki AM, Fenzi G, Grachtchouk M, Hutchin M, Dlugosz AA, Bianco AC, Missero C,  Larsen PR, Salvatore D. Sonic hedgehog-induced type 3 deiodinase blocks thyroid hormone action enhancing proliferation of normal and malignant keratinocytes. Proc Natl Acad Sci U S A. 2007 Sep 4;104(36):14466-71.

Nguyen BC, Lefort K, Mandinova A, Antonini D, Devgan V, Della Gatta G, Koster MI, Zhang Z, Wang J, Tommasi di Vignano A, Kitajewski J, Chiorino G, Roop DR, Missero C, Dotto GP. Cross-regulation between Notch and p63 in keratinocyte commitment to differentiation. Genes Dev. 2006 Apr 15;20(8):1028-42.

Antonini D, Rossi B, Han R, Minichiello A, Di Palma T, Corrado M, Banfi S, Zannini M, Brissette JL, Missero C. An autoregulatory loop directs the tissue-specific expression of p63 through a long-range evolutionarily conserved enhancer. Mol Cell Biol. 2006 Apr;26(8):3308-18.

Last update: January 02, 2017