|
2010 – 2013. After obtaining a Master's degree in Microbiology-Immunology, Benoît ALLARD obtained a PhD in Cell Biology and Pathophysiology at the University of Bordeaux in 2013. His doctoral work was carried out in the Cardio-Thoracic Research Center of Bordeaux (INSERM U1045), directed by Prof. Roger MARTHAN, under the supervision of Prof. Patrick BERGER. His thesis focused on the expression and function of the PAR-2 receptor (Protease Activated Receptor-2) in the pathophysiology of asthma. The aim was to understand how activation of this membrane receptor, in both smooth muscle cells and epithelial cells, might be involved in bronchial remodeling in the asthmatic patient. The use of primary bronchial epithelial cells cultured in an air-liquid interface, to obtain differentiated epithelia, has enriched this translational research and resulted in publications in leading journals of the field.
|
2014 – 2016. To further his training in respiratory disease research, he joined the Meakins-Christie Laboratories, an internationally recognized center in this field, housed in the Research Institute of the McGill University Health Center (RIMUHC, Montreal, Canada). In the team led by Prof. James G. MARTIN, Dr. ALLARD has developed a mouse model of adaptation to oxidative stress-induced lung injury, and has been able to explore the mechanisms of adaptation by assessing respiratory functions (FexiVent), inflammatory and antioxidant responses in bronchoalveolar lavage and lung tissue, and using knockout mice, cell depletion and adoptive transfer strategies, as well as a transcriptomic approach. He found that repeated exposure to oxidative stress led to rapid pulmonary adaptation, characterized by resolution of neutrophilic inflammation and absence of bronchial hyperreactivity. He demonstrated that this adaptation was dependent on a subpopulation of resident alveolar macrophages, with tolerogenic signaling. This work has enabled him to acquire considerable expertise in the measurement of pulmonary physiological responses, and to participate in numerous collaborations, including studies of the immune response during influenza A virus infection.
2017 – 2021. Building on his experience at McGill University, Benoît ALLARD returned to Prof. BERGER's team to study the impact of asthmatic bronchial smooth muscle on the epithelial response to rhinovirus infection. His work has opened up new therapeutic avenues by describing the molecular mechanisms that may explain rhinovirus-induced exacerbations in asthmatic patients. Following two other research projects, one on the attachment phase of pseudomonas aeruginosa, an opportunistic pathogen of the respiratory tract (Chimie et Biologie des Membranes et des Nano-objets - CNRS UMR 5248, Bordeaux University), and one on the role of innate lymphoid cells type 2 (ILC2) in fibrosis in patients with systemic scleroderma (Immunology from Concept and Experiment to Translation - ImmunoConcEpT - CNRS UMR 5164, Bordeaux University), Dr. Benoit ALLARD has been recruited as Associate Professor at the University of Reunion Island in 2021.
2021. In the DéTROI laboratory, he leverages his expertise in pulmonary pathophysiology and therapeutic approaches to study the aerosolization of ApoA1 nanoparticles enriched with molecules of interest and evaluate their effects in preclinical models. A first proof-of-concept project focuses on the therapeutic potential of ApoA1 nanoparticles enriched with alpha-1-antitrypsin to treat pulmonary emphysema due to alpha-1-antitrypsin deficiency. Dr ALLARD is recipient of the ANR JCJC 2024 (AAPG 2024 CE17 - Recherche translationnelle en santé) and received a prize from the AAT Laurell's Training Award, to carry out this project.
In addition to transposing the therapeutic potential of AAT-enriched A1NPs into laboratory models of stroke, the methodology and scientific tools developed in the emphysema project could be used to explore the therapeutic potential of aerosolizing enriched A1NPs in the emerging pulmonary complications of diabetes.
2017 – 2021. Building on his experience at McGill University, Benoît ALLARD returned to Prof. BERGER's team to study the impact of asthmatic bronchial smooth muscle on the epithelial response to rhinovirus infection. His work has opened up new therapeutic avenues by describing the molecular mechanisms that may explain rhinovirus-induced exacerbations in asthmatic patients. Following two other research projects, one on the attachment phase of pseudomonas aeruginosa, an opportunistic pathogen of the respiratory tract (Chimie et Biologie des Membranes et des Nano-objets - CNRS UMR 5248, Bordeaux University), and one on the role of innate lymphoid cells type 2 (ILC2) in fibrosis in patients with systemic scleroderma (Immunology from Concept and Experiment to Translation - ImmunoConcEpT - CNRS UMR 5164, Bordeaux University), Dr. Benoit ALLARD has been recruited as Associate Professor at the University of Reunion Island in 2021.
2021. In the DéTROI laboratory, he leverages his expertise in pulmonary pathophysiology and therapeutic approaches to study the aerosolization of ApoA1 nanoparticles enriched with molecules of interest and evaluate their effects in preclinical models. A first proof-of-concept project focuses on the therapeutic potential of ApoA1 nanoparticles enriched with alpha-1-antitrypsin to treat pulmonary emphysema due to alpha-1-antitrypsin deficiency. Dr ALLARD is recipient of the ANR JCJC 2024 (AAPG 2024 CE17 - Recherche translationnelle en santé) and received a prize from the AAT Laurell's Training Award, to carry out this project.
In addition to transposing the therapeutic potential of AAT-enriched A1NPs into laboratory models of stroke, the methodology and scientific tools developed in the emphysema project could be used to explore the therapeutic potential of aerosolizing enriched A1NPs in the emerging pulmonary complications of diabetes.
Summary of the current research project
Alpha-1-antitrypsin (AAT) deficiency is a rare genetic disorder (1 in 1600-2000 people in Europe, 10 000 patients in France) caused by mutation of the SERPINA1 gene, which codes for the AAT protein. AAT is mainly synthesized in the liver and secreted into the circulation, where its primary role is to protect lung tissue against proteolysis induced by neutrophil elastase. Point mutations can lead to low plasma levels of AAT and predispose to the development of pulmonary emphysema, characterized by progressive and irreversible proteolytic degradation of alveolar tissue resulting in decreased respiratory function and increased risk mortality. The standard of care for these patients is the intravenous administration of AAT protein. This replacement therapy reduces the annual loss of lung parenchyma and slows down the lung function decline but has no effect on exacerbation rates or health status. This proposal aims to evaluate a new treatment based on the aerosolization of AAT vectored into apolipoprotein A1 nanoparticles (A1NP, also called reconstituted high-density lipoproteins). A1NP have anti-oxidant, endotoxin scavenging and anti-inflammatory properties. The synergy of these protective effects with the anti-protease activity of AAT constitutes a promising therapy for which inhalation will allow direct action on the targeted tissue. Overall, this project has the potential to provide a proof of concept for the development of an innovative therapy for AAT-deficient patients.
- Main objective of the project: to provide a proof of concept for the innovative treatment of pulmonary emphysema in AATD by using inhalation of reconstituted apolipoprotein A1 nanoparticles enriched with AAT (A1NP-AAT).
- Hypothesis 1: Apolipoprotein A1 nanoparticles enriched with AAT have protective functions in vitro
- Hypothesis 2: Aerosolization of A1NP-AAT ensures homogeneous distribution in the lung.
- Hypothesis 3: The delivery of AAT by A1NP after lipopolysaccharide-induced lung inflammation in AAT KO mice may prevent neutrophil-associated tissue damage and preserve lung function.
Selected PUBLICATIONS
Aerosolized ApoA1 Nanoparticles Synthesized by Microfluidics Cross the Lung Barrier and Modulate Inflammation.
Apalama ML, Givran L, Navarette B, Bringart M, Giraud P, Rondeau P, Meilhac O, Allard B.
bioRxiv. 2025
Role of Metabolic and Inflammatory Mediators from Bronchial Smooth Muscle on Epithelial Infection.
Allard B.
Am J Respir Cell Mol Biol. 2025.
Pulmonary adaptation to repeated poly(I:C) exposure is impaired in asthmatic mice: an observational study.
Allard B, Ousova O, Savitskaya Z, Levardon H, Maurat E, Campagnac M, Trian T, Berger P.
Respiratory Research. 2024.
TGFβ promotes low IL10-producing ILC2 with profibrotic ability involved in skin fibrosis in systemic sclerosis.
Allard B*, Laurent P*, Manicki P, Jolivel V, Levionnois E, Jeljeli M, Henrot P, Izotte J, Seneschal J, Constans J, Chizzolini C, Richez C, Duffau P, Lazaro E, Forcade E, Schaeverbeke T, Pradeu T, Batteux F, Blanco P, Contin Bordes C, Truchetet ME.
Annals of the Rheumatic Diseases. 2021.
Asthmatic Bronchial Smooth Muscle Increases CCL5-Dependent Monocyte Migration in Response to Rhinovirus-Infected Epithelium.
Allard B*, Levardon H*, Esteves P, Celle A, Maurat E, Thumerel M, Girodet PO, Trian T, Berger P.
Front Immunol. 2020.
Tolerogenic signaling of alveolar macrophages induces lung adaptation to oxidative injury.
Allard B, Panariti A, Pernet E, Downey J, Ano S, Dembele M, Nakada E, Fujii U, McGovern TK, Powell W, Divangahi M, Martin JG.
J Allergy Clin Immunol. 2019.
Alveolar Macrophages in the Resolution of Inflammation, Tissue Repair, and Tolerance to Infection.
Allard B, Panariti A, Martin JG.
Front Immunol. 2018.
House dust mites induce proliferation of severe asthmatic smooth muscle cells via an epithelium-dependent pathway.
Allard B*, Trian T*, Dupin I, Carvalho G, Ousova O, Maurat E, Bataille J, Thumerel M, Begueret H, Girodet PO, Marthan R, Berger P.
Am J Respir Crit Care Med. 2015.
Protease activated receptor-2 expression and function in asthmatic bronchial smooth muscle.
Allard B, Bara I, Gilbert G, Carvalho G, Trian T, Ozier A, Gillibert-Duplantier J, Ousova O, Maurat E, Thumerel M, Quignard JF, Girodet PO, Marthan R, Berger P.
PLoS One. 2014.
Apalama ML, Givran L, Navarette B, Bringart M, Giraud P, Rondeau P, Meilhac O, Allard B.
bioRxiv. 2025
Role of Metabolic and Inflammatory Mediators from Bronchial Smooth Muscle on Epithelial Infection.
Allard B.
Am J Respir Cell Mol Biol. 2025.
Pulmonary adaptation to repeated poly(I:C) exposure is impaired in asthmatic mice: an observational study.
Allard B, Ousova O, Savitskaya Z, Levardon H, Maurat E, Campagnac M, Trian T, Berger P.
Respiratory Research. 2024.
TGFβ promotes low IL10-producing ILC2 with profibrotic ability involved in skin fibrosis in systemic sclerosis.
Allard B*, Laurent P*, Manicki P, Jolivel V, Levionnois E, Jeljeli M, Henrot P, Izotte J, Seneschal J, Constans J, Chizzolini C, Richez C, Duffau P, Lazaro E, Forcade E, Schaeverbeke T, Pradeu T, Batteux F, Blanco P, Contin Bordes C, Truchetet ME.
Annals of the Rheumatic Diseases. 2021.
Asthmatic Bronchial Smooth Muscle Increases CCL5-Dependent Monocyte Migration in Response to Rhinovirus-Infected Epithelium.
Allard B*, Levardon H*, Esteves P, Celle A, Maurat E, Thumerel M, Girodet PO, Trian T, Berger P.
Front Immunol. 2020.
Tolerogenic signaling of alveolar macrophages induces lung adaptation to oxidative injury.
Allard B, Panariti A, Pernet E, Downey J, Ano S, Dembele M, Nakada E, Fujii U, McGovern TK, Powell W, Divangahi M, Martin JG.
J Allergy Clin Immunol. 2019.
Alveolar Macrophages in the Resolution of Inflammation, Tissue Repair, and Tolerance to Infection.
Allard B, Panariti A, Martin JG.
Front Immunol. 2018.
House dust mites induce proliferation of severe asthmatic smooth muscle cells via an epithelium-dependent pathway.
Allard B*, Trian T*, Dupin I, Carvalho G, Ousova O, Maurat E, Bataille J, Thumerel M, Begueret H, Girodet PO, Marthan R, Berger P.
Am J Respir Crit Care Med. 2015.
Protease activated receptor-2 expression and function in asthmatic bronchial smooth muscle.
Allard B, Bara I, Gilbert G, Carvalho G, Trian T, Ozier A, Gillibert-Duplantier J, Ousova O, Maurat E, Thumerel M, Quignard JF, Girodet PO, Marthan R, Berger P.
PLoS One. 2014.