Michela Zamboni

Research Area: ??


Monterotondo Scalo – Campus “A.Buzzati Traverso”
+39 06 90091344
michela.zamboni@cnr.it

Keywords: LUNG, THYROID, BRAIN

Our lab is involved in the characterization of the activity of a transcription factor we have previously identified, named TTF-1/Nkx2.1.

TTF-1 (thyroid transcription factor-1) is a member of the homeodomain-containing transcription factor family, and activates the expression of tissue specific genes in the follicular cells of thyroid, in the epithelial cells of the lung and in restricted regions of the brain.

TTF-1 is expressed at the earliest stages of thyroid, lung and brain development. Nkx2.1 null mutant embryos die at birth due to respiratory insufficiency caused by profoundly abnormal lungs. In addition,Nkx21– null mice lack the thyroid and pituitary gland and exhibit severe defects in the ventral forebrain. Mutations in TTF1 gene are associated   with benign hereditary chorea (BHC), respiratory distress syndrome (IRDS) and congenital hypothyroidism (CH). These three pathologies are referred as Brain-Thyroid-Lung syndrome. We are involved in the characterization of the role of TTF-1 in all three districts in which it is expressed:

  1. THYROID: in thyrocytes we study the interaction of TTF-1 with other thyroid-specific transcription factors ( TTF-2/FOXE-1 and Pax8) in the regulation of thyroid homeostasis.
  2. LUNG. TTF-1 in lung adenocarcinoma plays a dual role as oncogene and onco-suppressor. By stable RNAi in NSCLC cell lines we attempt to identify TTF-1 specific targets.
  3. BRAIN . Besides the identification and molecular characterization of mutations in TTF-1 in patients with benign hereditary chorea we also want to identify TTF-1 target genes in neurons involved in BHC.KEY-WORDS: LUNG, THYROID, BRAIN

Education

Date of Birth:  5th January 1960, Trento (TN)

Current Position: Institute of Biochemistry and Cell Biology, Italian National Council of Research. Staff Member

Previous Positions & Qualification:

  • 1980-1985 Univeristà degli Studi ,University of Milan
    Degree, Biology

  • 1986-2000 Institute of Cell Biology, CNR, Rome
    Resercher at Enichem, Molecular Biology

  • 2000-2009 Institute of Cell Biology, CNR, Rome
    Post-graduate, Molecular Biology

  • 2009-2019 Institute of Cell Biology and Neurobiology, CNR, Rome
    Staff Member , Molecular Biology

  • 2019-present Institute of Biochemistry and Cell Biology CNR, Monterotondo (Rome)
    Staff Member, Molecular Biology

     

     

     

  • Fruscoloni P*, Zamboni M*, Baldi MI, Tocchini-Valentini GP. Exonucleolytic degradation of double-stranded RNA by an activity in Xenopus laevis germinal vesicles. (* P.F. and M.Z. contributed equally to this work ) Proc Natl Acad Sci U S A. 2003 Feb 18;100(4):1639-44. (* P. F. and M.Z. contributed equally to this work).
  • Zamboni M, Scarabino D, Tocchini-Valentini GP. Splicing of mRNA mediated by tRNA sequences in mouse cells. RNA 2009 Dec;15(12):2122-8. doi: 10.1261/rna.1841609. Epub 2009 Oct 22.
  • Di Segni G, Gastaldi S, Zamboni M, Tocchini-Valentini GP. Yeast pheromone receptor genes STE2 and STE3 are differently regulated at the transcription and polyadenylation level. Proc Natl Acad Sci U S A. 2011 Oct 11;108(41):17082-6. doi: 10.1073/pnas.1114648108. Epub 2011 Oct 3.
  • Provenzano C, Zamboni M, Veneziano L, Mantuano E, Garavaglia B, Zorzi G, Pagonabarraga J, Giunti P, Civitareale D. Functional characterization of two novel mutations in TTF-1/NKX2.1 homeodomain in patients with benign hereditary chorea. J Neurol Sci. 2016 Jan 15;360:78-83. doi: 10.1016/j.jns.2015.11.050. Epub 2015 Nov 27.
  • Zamboni M, Civitareale D. TTF-1/Nkx2.1 functional connection with mutated EGFR relies on LRIG1 and β-catenin pathways in lung cancer cells. Biochem Biophys Res Commun. 2018 Nov 10;505(4):1027-1031. doi: 10.1016/j.bbrc.2018.10.015.

view more pubications

1) Zamboni M., Privitera E., Mosna G, Ghidoni A. Sister chromatid exchange in methotrexate resistant and sensitive C3H10T1/2 mouse cells. Genetica 80: 229-233 4 1990).

 

2) Fruscoloni P, Zamboni M., Panetta G., De Paolis A., Tocchini-Valentini G.P. Mutational analysis of the transcription start site of the yeast tRNA (Leu3) gene. Nucleic Acid Res. 23: 2914-2918 (1995)

 

3) Fruscoloni P*, Zamboni M*, Baldi MI, Tocchini-Valentini GP. Exonucleolytic degradation of double-stranded RNA by an activity in Xenopus laevis germinal vesicles. (* P.F. and M.Z. contributed equally to this work ) Proc Natl Acad Sci U S A. 2003 Feb 18;100(4):1639-44. Epub 2003 Feb 10.

 

4) Zamboni M, Scarabino D, Tocchini-Valentini GP. Splicing of mRNA mediated by tRNA sequences in mouse cells. RNA 2009 Dec;15(12):2122-8. doi: 10.1261/rna.1841609. Epub 2009 Oct 22.

 

5) Morgan H, Beck T, Blake A, Gates H, Adams N, Debouzy G, Leblanc S, Lengger C, Maier H, Melvin D, Meziane H, Richardson D, Wells S, White J, Wood J; EUMODIC Consortium, de Angelis MH, Brown SD, Hancock JM, Mallon AM. EuroPhenome: a repository for high-throughput mouse phenotyping data. Nucleic Acids Res. 2010 Jan;38(Database issue):D577-85. doi: 10.1093/nar/gkp1007. Epub 2009 Nov 23.

 

6) Di Segni G, Gastaldi S, Zamboni M, Tocchini-Valentini GP. Yeast pheromone receptor genes STE2 and STE3 are differently regulated at the transcription and polyadenylation level. Proc Natl Acad Sci U S A. 2011 Oct 11;108(41):17082-6. doi: 10.1073/pnas.1114648108. Epub 2011 Oct 3.

 

7) Gates H, Mallon AM, Brown SD; EUMODIC Consortium. High-throughput mouse phenotyping. Methods. 2011 Apr;53(4):394-404. doi: 10.1016/j.ymeth.2010.12.017. Epub 2010 Dec 23.

 

8) Wells S,et al.; EUMODIC Consortium, Holmes C, Steel KP, Herault Y, Gailus-Durner V, Mallon AM, Brown SD. Analysis of mammalian gene function through broad-based phenotypic screens across a consortium of mouse clinics. Nat Genet. 2015 Sep;47(9):969-78. doi: 10.1038/ng.3360. Epub 2015 Jul 27.

 

9) de Angelis MH, et al., EUMODIC Consortium, Holmes C, Steel KP, Herault Y, Gailus-Durner V, Mallon AM, Brown SD. Analysis of mammalian gene function through broad-based phenotypic screens across a consortium of mouse clinics. Nat Genet. 2015 Sep;47(9):969-78. doi: 10.1038/ng.3360. Epub 2015 Jul 27

 

10) Provenzano C, Zamboni M, Veneziano L, Mantuano E, Garavaglia B, Zorzi G, Pagonabarraga J, Giunti P, Civitareale D. Functional characterization of two novel mutations in TTF-1/NKX2.1 homeodomain in patients with benign hereditary chorea. J Neurol Sci. 2016 Jan 15;360:78-83. doi: 10.1016/j.jns.2015.11.050. Epub 2015 Nov 27.

 

11) Gastaldi S*, Zamboni M*, Di Segni G, Bolasco G, Tocchini-Valentini GP. Analysis of random PCR-originated mutants of the yeastSte2 and Ste3 receptors. Microbiology open. 2016 Aug;5(4):670-86. doi: 10.1002/mbo3.361. (* S.G. and M.Z. contributed equally to this work ).

 

12) Zamboni M, Civitareale D. TTF-1/Nkx2.1 functional connection with mutated EGFR relies on LRIG1 and β-catenin pathways in lung cancer cells. Biochem Biophys Res Commun. 2018 Nov 10;505(4):1027-1031. doi: 10.1016/j.bbrc.2018.10.015.

Dr. Michela Zamboni (staff researcher IBBC-CNR)

Dr. Donato Civitareale (staff researcher IBBC-CNR)