Patrick Brest
  • E-mail :[email]
  • Phone : + 33 4 92 03 12 45
  • Location : Nice, France
Last update 2017-03-29 15:28:56.343

Patrick Brest Full Time INSERM Senior Resercher

Course and current status

2014: Habilitation à Diriger les Recherches (HDR)

2012: INSERM Researcher at  IRCAN Institute of Research on Cancer and Aging in Nice (IRCAN), CNRS UMR7284, INSERM U1081, University of Nice Sophia-Antipolis, Faculty of Medicine, 28 av de Valombrose 06107 Nice, FR (actual position)

2010-2011: INSERM Researcher at University of Nice Sophia-Antipolis EA4319/INSERM ERI21, Faculty of Medicine, Nice, FR

2007-2010: Postdoctoral fellow at INSERM ERI-21/EA-4319, Nice, FR

2004_2007: Postdoctoral fellow at Lund University, Lund, SE

2000-2004: Ph.D student at Université de Nice Sophia-Antipolis, Nice, FR

2000: Master of Science at Université de Nice Sophia-Antipolis, Nice, FR

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Bibliometry

Articles: 47

Sum of the Times Cited: 2939

h-index:19

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GRANTS

INSERM, CNRS, UNS

SYNOTELO Project (Agence Nationale de Recherche) (Cancéropole PACA)

Tumor microenvironment Project (Fondation ARC pour la recherche sur le cancer)

Scientific summary

From my Ph.D. to today, I have aimed to understand the fundamental mechanisms of gene regulation in human inflammatory or tumoral pathologies. During my thesis (Pr. Hofman - INSERM EPI-0215 ​​- MENRT / Monitorat, League against Cancer, 2000-2004), I showed that different pathogens (E. coli, H. pylori) hijacked the functions of epithelial cells for their own profit(13 articles, 4 in PDC, 2 in co-PDC).

Then I chose to do a post-doctoral internship at Prof. Svanborg's translational research laboratory at the BioMedical Center, Lund, Sweden (American Cancer Society, Gunnar Nilsson Cancer Foundation, FRM, 2004-2007). I have shown that the inhibitors of histone deacetylases (HDACi) potentiate the effect of a new anti-cancer agent called HAMLET, triggering the massive death of tumor cells by apoptosis and autophagy (3 articles). These results have enabled me to propose new therapeutic applications against cancer (International Patent 2006, Principal Inventor, submitted by NatImmune, DK).

Back in France, in 2007 I joined the ERI21 / CRB-Tumorothèque unit in Nice led by Prof. Hofman where I demonstrated that the antitumor effect of HDACi is dependent on a signature of lethal miRNA specifically expressed in cancer cells (INCa Fev 2008-May 2010, 3 articles, European Patent 2009).

Since my recruitment as CR1 Researcher in 2010, I have devoted my activities of supervising future researchers (1 erasmus, 4 masters, 2 students in thesis, 1 postdoctoral) to study mechanisms of original regulations of the miRNAs in Human pathologies (ARC Free Program, ANR JCJC, Cancéropole PACA):

1 / Demonstration that a polymorphism synonymous on the GWAS-associated IRGM gene with Crohn's disease can disrupt the regulation of RNA by loss of miRNA binding, resulting in aberrant IRGM expression. These results lead us to revisit in a very significant way our vision of the consequences of mutations synonymous in pathophysiological mechanisms. (Nature Genetics, 2011; Autophagy, 2011, 4 reviews)

2 / Determination of miRNA signatures to classify patients in pulmonary pathologies (PlosOne, 2013, PDC), and miRNA predisposing to an effective therapeutic response (Oncotarget, 2016, PDC). These results suggest the use of miRNAs as a complementary tool for clinical diagnosis, prognosis or therapy.

3 / Demonstration of transient reprogramming (ie EMT) of tumor cells through a novel mechanism combining the phagocytosis of extracellular miRNAs when contacting inflammatory cells / tumor cells and its degradation by an XRN1 exonuclease. These results demonstrate that the plasticity of tumor cells is due to the instability of extracellular microRNAs once phagocytosed, a new notion explaining the transient and transient mesenchymal and then epithelial transitions of tumor cells (Nucleic Acids Research, 2017).

My future research project aims to be in continuity with my previous work and in particular on the regulation of non-coding RNA. My research project aims to understand the fundamental mechanisms controlling the formation of micro-emboli and the survival of cancer cells associated with neutrophils. In particular, we will study the central role of exonucleases in maintaining the expression of pro-tumor extracellular miRNAs in in vitro co-culture models (neutrophils / tumor cells) but also in these isolated CTCs from patients. This project aims to develop new markers of "aggressiveness" of CTCs to stratify patients according to their risk of recurrenceC

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