Dr. Gerardo Ferbeyre

biochimie, Université de Montréal, Montréal, Quebec, Canada

Dr. Gerardo Ferbeyre

biochimie, Université de Montréal, Montréal, Quebec, Canada

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Academic Career Length

35Years (1992-Present)

(Calculated once Scilit publication data is synced: current year − year of first publication + 1)

Representative Publications

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23 March 2013 in Aging Cell

Journal Article

Metformin inhibits the senescence‐associated secretory phenotype by interfering with IKK/NF‐κB activation

Olga Moiseeva

Xavier Deschênes-Simard

Emmanuelle St‐Germain

Sebastian Igelmann

Geneviève Huot

Gerardo Ferbeyre

Summary: We show that the antidiabetic drug metformin inhibits the expression of genes coding for multiple inflammatory cytokines seen during cellular senescence. Conditioned medium (CM) from senescent cells stimulates the growth of prostate cancer cells but treatment of senescent cells with metformin inhibited this effect. Bioinformatic analysis of genes downregulated by metformin suggests that the drug blocks the activity of the transcription factor NF‐κB. In agreement, metformin prevented the translocation of NF‐κB to the nucleus and inhibited the phosphorylation of IκB and IKKα/β, events required for activation of the NF‐κB pathway. These effects were not dependent on AMPK activation or on the context of cellular senescence, as metformin inhibited the NF‐κB pathway stimulated by lipopolysaccharide (LPS) in ampk null fibroblasts and in macrophages. Taken together, our results provide a novel mechanism for the antiaging and antineoplastic effects of metformin reported in animal models and in diabetic patients taking this drug.

1 May 2019 in Cytokine

Journal Article

The senescence-associated secretory phenotype and its regulation

Stéphane Lopes-Paciencia

Emmanuelle Saint-Germain

Marie-Camille Rowell

Ana Fernández Ruiz

Paloma Kalegari

Gerardo Ferbeyre

1 August 2009 in Molecular and Cellular Biology

Journal Article

Mitochondrial Dysfunction Contributes to Oncogene-Induced Senescence

Olga Moiseeva

Véronique Bourdeau

Antoine Roux

Xavier Deschênes-Simard

Gerardo Ferbeyre

The expression of oncogenic ras in normal human cells quickly induces an aberrant proliferation response that later is curtailed by a cell cycle arrest known as cellular senescence. Here, we show that cells expressing oncogenic ras display an increase in the mitochondrial mass, the mitochondrial DNA, and the mitochondrial production of reactive oxygen species (ROS) prior to the senescent cell cycle arrest. By the time the cells entered senescence, dysfunctional mitochondria accumulated around the nucleus. The mitochondrial dysfunction was accompanied by oxidative DNA damage, a drop in ATP levels, and the activation of AMPK. The increase in mitochondrial mass and ROS in response to oncogenic ras depended on intact p53 and Rb tumor suppression pathways. In addition, direct interference with mitochondrial functions by inhibiting the expression of the Rieske iron sulfur protein of complex III or the use of pharmacological inhibitors of the electron transport chain and oxidative phosphorylation was sufficient to trigger senescence. Taking these results together, this work suggests that mitochondrial dysfunction is an effector pathway of oncogene-induced senescence.

1 January 2007 in Genes & Development

Journal Article

The DNA damage signaling pathway is a critical mediator of oncogene-induced senescence

Frédérick A. Mallette

Marie-France Gaumont-Leclerc

Gerardo Ferbeyre

Here we report that RNA interference against ATM inhibited p53 accumulation in cells expressing oncogenic STAT5 and cooperated with Rb inactivation to suppress STAT5A-induced senescence. Knocking down ATM was also effective to bypass E2F1-induced senescence and in combination with Rb inactivation, inhibited RasV12-induced senescence. Cells that senesced in response to ca-STAT5A or RasV12 accumulated DNA damage foci and activated ATM, ATR, Chk1, and Chk2, indicating that aberrant oncogene activation induces a DNA damage signaling response. Intriguingly, bypassing oncogene-induced senescence by inactivation of p53 and Rb did not eliminate the accumulation of oncogene-induced DNA damage foci (ODDI), suggesting a mechanism that may limit transformation in immortalized cells.

1 April 2012 in Cancer Prevention Research

Journal Article

Metformin Reduces Endogenous Reactive Oxygen Species and Associated DNA Damage

Carolyn Algire

Olga Moiseeva

Xavier Deschênes-Simard

Lilian Amrein

Luca Petruccelli

Michael N. Pollak

Pharmacoepidemiologic studies provide evidence that use of metformin, a drug commonly prescribed for type II diabetes, is associated with a substantial reduction in cancer risk. Experimental models show that metformin inhibits the growth of certain neoplasms by cell autonomous mechanisms such as activation of AMP kinase with secondary inhibition of protein synthesis or by an indirect mechanism involving reduction in gluconeogenesis leading to a decline in insulin levels and reduced proliferation of insulin-responsive cancers. Here, we show that metformin attenuates paraquat-induced elevations in reactive oxygen species (ROS), and related DNA damage and mutations, but has no effect on similar changes induced by H₂0₂, indicating a reduction in endogenous ROS production. Importantly, metformin also inhibited Ras-induced ROS production and DNA damage. Our results reveal previously unrecognized inhibitory effects of metformin on ROS production and somatic cell mutation, providing a novel mechanism for the reduction in cancer risk reported to be associated with exposure to this drug. Cancer Prev Res; 5(4); 536–43. ©2012 AACR.

19 October 2021 in Nature Reviews Cardiology

Journal Article

The role of cellular senescence in cardiac disease: basic biology and clinical relevance

Mozhdeh Mehdizadeh

Martin Aguilar

Eric Thorin

Gerardo Ferbeyre

Stanley Nattel

About Me

Dr. Gerardo Ferbeyre is a Full Professor at the Department of Biochemistry and Molecular Medicine, Université de Montréal. He graduated with honors from the medical school at the University of Havana in 1987 and obtained a Ph.D. in Biochemistry from the University of Montreal where he studied ribozymes. He underwent postdoctoral training at Cold Spring Harbor Laboratory. There, he established a link between the promyelocytic leukemia protein PML and oncogene-induced senescence and studied the role of p53 and p19ARF as mediators of cellular senescence. In 2001, he joined the University of Montreal. Major contributions from his laboratory include the discovery that DNA damage signaling mediates senescence (Genes and Dev. 2007), the role of SOCS1 linking inflammation to p53 (Mol Cell 2009, Aging 2017, Cancer Res 2019), the role of proteasome-dependent protein degradation as a key mediator of tumor suppression and senescence (Genes and Dev 2013), the mechanism of senescence induction by the anticancer drug palbociclib (Cancer Res 2016), the discovery of ribosome biogenesis defects associated with senescence (Nature Cell Biol 2018, Cell Cycle 2023), a new metabolic cycle that promotes senescence escape (Mol Cell 2021) and the process of senescence commitment (Cell Reports 2024). His current research interests include senescence and anti-cancer therapies, ribosome biogenesis, cancer metabolism and Metformin in cancer therapy.

Dr. Gerardo Ferbeyre

Dr. Gerardo Ferbeyre

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