Molecular Basis of Inflammation

 Nadine LAGUETTE

 IGH - UMR 9002

 141, rue de la Cardonille, 34396 Montpellier

Phone: +33 4 34 35 98 11

Email: nadine.laguette@igh.cnrs.fr

Website

Increased risk of malignancy and poor patient prognosis is associated with chronic inflammation. While the cause for tumor-promoting inflammation may be “extrinsic” (eg. Environmental factors), the role of “intrinsic factors” has been evidenced in recent years. For instance, persistent DNA damage signaling or inability to repair broken DNA within cancerous cells can sustain tumor-promoting chronic inflammation through the generation of immunogenic nucleic acid species. Upon detection by the innate immune system, those will lead to the production of pro-inflammatory cytokines that will in turn affect the tumor micro-environment to promote angiogenesis, tumor growth and eventually metastasis.

Our aim is to explore the link between the mechanisms that maintain genomic stability and the regulation of chronic inflammation. Our primary models of study are cancer susceptibility syndromes and viral infections. Our work aims at identifying endogenous and exogenous immunogenic nucleic acids, their biogenesis and regulation in non-cancerous and cancerous cells. We will identify the engaged pathways that lead to dysregulation of pro-inflammatory cytokine levels in these conditions and the consequences for tumorigenesis and resistance to chemotherapy.

Keywords: Inflammation, innate immunity, immunogenic nucleic acids, cancer, retroviruses

Main publications

• Brégnard C, Guerra J, Déjardin S, Passalacqua F, Benkirane M, Laguette N. Upregulated LINE-1 activity in the Fanconi Anemia cancer susceptibility syndrome leads to spontaneous pro-inflammatory cytokine production. EBioMedicine. In press.
• Laguette N*, Benkirane M*. Shaping of the host cell by viral accessory proteins. Front Microbiol. 2015 Feb 23;6:142.
• Brégnard C, Benkirane M*, Laguette N*. 2014 DNA damage repair machinery and HIV escape from innate immune sensing. Front Microbiol. 5:176. Review.
• Laguette N*, Brégnard C, Hue P, Basbous J, Yatim A, Larroque M, Kirchhoff F, Constantinou A, Sobhian B and Benkirane* M. 2014. Premature Activation of the SLX4 Complex by Vpr Promotes G2/M Arrest and Escape from Innate Immune Sensing Cell 156(1-2):134-45.
• Cribier A, Descours B, Valadao AL, Laguette N, Benkirane M. 2013. Phosphorylation of SAMHD1 by Cyclin A2/CDK1 Regulates Its Restriction Activity toward HIV-1. Cell Rep 3: 1036-43.
• Descours B, Cribier A, Chable-Bessia C, Ayinde D, Rice G, Crow Y, Yatim A, Schwartz O, Laguette N, Benkirane M. 2012. SAMHD1 restricts HIV-1 reverse transcription in quiescent CD4(+) T-cells. Retrovirology 9: 87.
• Laguette N*, Rahm N*, Sobhian B, Chable-Bessia C, Munch J, Snoeck J, Sauter D, Switzer WM, Heneine W, Kirchhoff F, Delsuc F, Telenti A, Benkirane M. 2012. Evolutionary and Functional Analyses of the Interaction between the Myeloid Restriction Factor SAMHD1 and the Lentiviral Vpx Protein. Cell Host Microbe.
• Laguette N*, Benkirane M*. 2011. How Samhd1 changes our view of viral restriction. Trends Immunol.
• Laguette N*, Sobhian B, Casartelli N, Ringeard M, Chable-Bessia C, Segeral E, Yatim A, Emiliani S, Schwartz O, Benkirane M*. 2011. SAMHD1 is the dendritic- and myeloid-cell-specific HIV-1 restriction factor counteracted by Vpx. Nature 474: 654-7.
• Sobhian B, Laguette N, Yatim A, Nakamura M, Levy Y, Kiernan R, Benkirane M. 2010. HIV-1 Tat assembles a multifunctional transcription elongation complex and stably associates with the 7SK snRNP. Mol Cell 38: 439-51.