Progeria project

 

Progeria, also known as Hutchinson-Gilford Progeria Syndrome (HGPS), is a rare, fatal genetic disease characterized by an appearance of accelerated aging in children. This syndrome is typically caused by mutations in codon 608 (G608G) of the LMNA leading to the production of a mutated form of Lamin A precursor called Progerin. In HGPS, Progerin accumulates in cells and causes progressive a wide range of molecular defects including nuclear shape abnormalities, chromatin disorganization, DNA damages and delay in cell proliferation. In collaboration with Pr Nicolas Lévy, our team have generated induced pluripotent stem cells from progeria patients’ cells. Thanks to this unlimited and standardized biological resource we are studying the molecular mechanisms of this syndrome and are developing high throughput screening of pharmacological compound’s to identify new potential treatments of this disease.

 

 

Equipe :

 

Xavier Nissan : Research Director (CECS)

 

 

Former members :

  • Solenn GUILBERT (Postdoc CECS),
  • Alessandra Lo Cicero (Postdoc CECS),
  • Anne Laure JASKOWIAK (Engineer CECS),
  • Anne Laure EGESIPE (Engineer CECS),
  • Amélie LE CORF (Engineer CECS),
  • Clémence DUPRE (Engineer CECS),
  • Sophie Blondel (PhD student),
  • Jennifer RAGOT (Engineer CECS)

 

Publications :

 

– Vulnerability of progeroid smooth muscle cells to biomechanical forces is mediated by MMP13. Pitrez PR, Estronca L, Monteiro LM, Colell G, Vazão H, Santinha D, Harhouri K, Thornton D, Navarro C, Egesipe AL, Carvalho T, Dos Santos RL, Lévy N, Smith JC, de Magalhães JP, Ori A, Bernardo A, De Sandre-Giovannoli A, Nissan X, Rosell A, Ferreira L.Nat Commun. 2020 Aug 17;11(1):4110. doi: 10.1038/s41467-020-17901-2.

– Hutchinson-Gilford progeria syndrome: Rejuvenating old drugs to fight accelerated ageing.

Guilbert SM, Cardoso D, Lévy N, Muchir A, Nissan X.Methods. 2020 Apr 9:S1046-2023(19)30302-0. doi: 10.1016/j.ymeth.2020.04.005. Online ahead of print.

– Pathological modelling of pigmentation disorders associated with Hutchinson-Gilford Progeria Syndrome (HGPS) revealed an impaired melanogenesis pathway in iPS-derived melanocytes.

Lo Cicero A, Saidani M, Allouche J, Egesipe AL, Hoch L, Bruge C, Sigaudy S, De Sandre-Giovannoli A, Levy N, Baldeschi C, Nissan X.Sci Rep. 2018 Jun 14;8(1):9112. doi: 10.1038/s41598-018-27165-y.

– MG132-induced progerin clearance is mediated by autophagy activation and splicing regulation.

Harhouri K, Navarro C, Depetris D, Mattei MG, Nissan X, Cau P, De Sandre-Giovannoli A, Lévy N.EMBO Mol Med. 2017 Sep;9(9):1294-1313. doi: 10.15252/emmm.201607315.

– Metformin decreases progerin expression and alleviates pathological defects of Hutchinson-Gilford progeria syndrome cells.

Egesipe AL, Blondel S, Lo Cicero A, Jaskowiak AL, Navarro C, Sandre-Giovannoli A, Levy N, Peschanski M, Nissan X.NPJ Aging Mech Dis. 2016 Nov 10;2:16026. doi: 10.1038/npjamd.2016.26. eCollection 2016.

– Biomechanical Strain Exacerbates Inflammation on a Progeria-on-a-Chip Model.

Ribas J, Zhang YS, Pitrez PR, Leijten J, Miscuglio M, Rouwkema J, Dokmeci MR, Nissan X, Ferreira L, Khademhosseini A.Small. 2017 Apr;13(15):10.1002/smll.201603737. doi: 10.1002/smll.201603737. Epub 2017 Feb 17.


– A High Throughput Phenotypic Screening reveals compounds that counteract premature osteogenic differentiation of HGPS iPS-derived mesenchymal stem cells.

Lo Cicero A, Jaskowiak AL, Egesipe AL, Tournois J, Brinon B, Pitrez PR, Ferreira L, de Sandre-Giovannoli A, Levy N, Nissan X.Sci Rep. 2016 Oct 14;6:34798. doi: 10.1038/srep34798.

– Drug screening on Hutchinson Gilford progeria pluripotent stem cells reveals aminopyrimidines as new modulators of farnesylation.

Blondel S, Egesipe AL, Picardi P, Jaskowiak AL, Notarnicola M, Ragot J, Tournois J, Le Corf A, Brinon B, Poydenot P, Georges P, Navarro C, Pitrez PR, Ferreira L, Bollot G, Bauvais C, Laustriat D, Mejat A, De Sandre-Giovannoli A, Levy N, Bifulco M, Peschanski M, Nissan X.Cell Death Dis. 2016 Feb 18;7(2):e2105. doi: 10.1038/cddis.2015.374.

– Pluripotent stem cells to model Hutchinson-Gilford progeria syndrome (HGPS): Current trends and future perspectives for drug discovery.

Lo Cicero A, Nissan X.Ageing Res Rev. 2015 Nov;24(Pt B):343-8. doi: 10.1016/j.arr.2015.10.002. Epub 2015 Oct 22.


– Induced pluripotent stem cells reveal functional differences between drugs currently investigated in patients with hutchinson-gilford progeria syndrome.

Blondel S, Jaskowiak AL, Egesipe AL, Le Corf A, Navarro C, Cordette V, Martinat C, Laabi Y, Djabali K, de Sandre-Giovannoli A, Levy N, Peschanski M, Nissan X.Stem Cells Transl Med. 2014 Apr;3(4):510-9. doi: 10.5966/sctm.2013-0168. Epub 2014 Mar 5.

– Unique preservation of neural cells in Hutchinson- Gilford progeria syndrome is due to the expression of the neural-specific miR-9 microRNA.

Nissan X, Blondel S, Navarro C, Maury Y, Denis C, Girard M, Martinat C, De Sandre-Giovannoli A, Levy N, Peschanski M.

Cell Rep. 2012 Jul 26;2(1):1-9. doi: 10.1016/j.celrep.2012.05.015. Epub 2012 Jun 21.

– [miR-9: the sentinel of neurons in progeria].

Blondel S, Navarro C, Lévy N, Peschanski M, Nissan X.Med Sci (Paris). 2012 Jun-Jul;28(6-7):663-6. doi: 10.1051/medsci/2012286022. Epub 2012 Jul 16.

Collaborations: