HIPS Talks with Dr. Nathalie Heuzé-Vourc’h and Prof. Dr. Mustapha Si-Tahar

“Inhalation of biotherapeutics to treat respiratory infections” and “Towards a metabolic anti-influenza therapy”

Thursday (!), February 6, 2020, at 17:15 s.t. in Bldg E8.1, Seminar Room (Ground Floor)

Dr. Nathalie Heuzé-Vourc’h and Prof. Dr. Mustapha Si-Tahar (Inserm U1100, Research Center for Respiratory Diseases, Tours, France)  will give a presentation entitled

“Inhalation of biotherapeutics to treat  respiratory infections”
“Towards a metabolic anti-influenza therapy”

When?: Thursday (!), February 6, 2020, at 17:15 s.t.
Where?: in Bldg E8.1, Seminar Room (Ground Floor)
Host: Prof. Dr. Claus-Michael Lehr  

There is opportunity to talk with the speaker before the talk.   
For details and for making appointments please contact Annette Herkströter at 0681-98806-1002 or per email: office-ddel@helmholtz-hips.de   
Guests are welcome!

Inhalation of biotherapeutics to treat respiratory infections
Lung infections, in particular those due to Pseudomonas aeruginosa (Pa), are increasingly difficult to treat due to evolving antibiotic resistance. Bacteriophages (phages) and antibodies (Ab) are part of the foreseen complementary/alternative biotherapies to antibiotics. Local delivery of those biotherapeutics, through inhalation, may improve their therapeutics index, matching the delivery route to the pathogen location.
Herein, we will present some preclinical results highlighting the superiority of the pulmonary route to deliver both anti-infectious Ab and phages in animal models, the fate/behavior of inhaled biotherapeutics after pulmonary deposition and their resistance to aerosolization.
Overall, delivering biotherapeutics through inhalation is efficient against Pa, but it is challenging to maintain biotherapeutic integrity during aerosolization, requiring optimization of the drug and device. Further studies are required to understand better the impact of biological barriers on the response to inhaled biotherapeutics and develop new strategies to improve biotherapeutics stability during aerosolization.

Nathalie Heuzé-Vourc’h, Research Director at INSERM, the National Institute of Biomedical Research in France. She leads a multidisciplinary team in the Research Centre for Respiratory Diseases (CEPR, INSERM U1100) in Tours, dedicated to ‘Aerosoltherapy and Biotherapeutcs for Respiratory Diseases’ (team 3). After graduating with her Ph.D. in oncology in France, she focused her research on lung diseases and obtained a
postdoctoral position in the division of pulmonary and critical care medicine (Dr Steven M. Dubinett) at UCLA, California. She gained interest in biotherapeutics working in a start-up (Agensys Inc., Santa Monica, California) developing anticancer monoclonal antibodies and was recruited in 2005 by INSERM as a young research scientist to continue working on this topic. Joining Pr Patrice Diot’s research group specialized in the delivery of drugs by aerosol in Tours, offered her new perspectives on her research projects as she started investigating the local delivery of biotherapeutics through the airways. She is currently supervising several projects on the multifaceted aspects of the delivery of biotherapeutics through the airways for treatments of lung diseases, from formulation to preclinical safety, with both academic and private partners. She has published more than 60 peer-reviewed papers and book chapters. She is one of the leaders of the Laboratory of Excellence ’MabImprove’, since 2011, from the French program ‘Investments for the Future.’ She is
the co-founder of Cynbiose Respiratory, a CRO specialized in experimental models in the respiratory field and serves regularly as a consultant to the pharma industry on aerosol therapy.  


Towards a metabolic anti-influenza therapy
Influenza A virus (IAV) is the etiological agent of a highly contagious acute respiratory disease, which causes a considerable socioeconomic burden despite annual vaccination campaigns. Therefore, it is essential to better understand IAV- host cells interaction to help design innovative antiviral therapies. In that regard, recent studies revealed the interplay between metabolic and immune signaling pathways. However, it remains unknown whether IAV alters lung tissues metabolism and what is its potential functional consequence.  
Using in vitro and in vivo models as well as human respiratory fluids and in-depth metabolomics analysis, we first found that IAV infection alters the glycolysis and mitochondrial oxidative respiration in lung tissues, leading to the accumulation of several immunometabolites in the bronchoalveolar airspaces. We next focused on one mitochondria-derived metabolite (coined here “MDA”) as its accumulation was found not only in the lungs of IAV-challenged mice but also in the tracheal fluids of IAV-infected patients. Remarkably, we found that MDA exhibits a potent antiviral activity both in vitro and in vivo as it inhibits H1N1 and H3N2 IAV strains and it
strongly decreases IAV-triggered inflammatory response. The underlying inhibiting mechanism involves a disruption of IAV replication cycle. Finally, we showed that mice receiving MDA are more resistant to IAV pneumonia than mock-treated animals. Hence, our study identifies the metabolite MDA as a novel component of the host antiviral arsenal.

Dr. M. Si-Tahar is the Director of the Research Center for Respiratory Diseases (3 teams, ~60 people ; Tours, France).
He is also the leader of the research team entitled: “Lung Infection & Immunity”. The goal of his team is to develop an innovative transversal research in the field of respiratory infections.  
After his Ph.D. training in vascular inflammation at the Pasteur Institute (Paris, France) in 1997, he developed two post-doctoral research projects on mucosal immune responses at Emory University (Atlanta, USA) and subsequently at the Massachusetts General Hospital/HMS (Boston, USA). In 2001, he has been recruited by INSERM and joined again the Pasteur Institute to initiate a program on major sensors (i.e. TLRs, RLRs) and signaling pathways triggered in bacteria and virus-infected lung epithelia, using both in vitro and in vivo approaches. He has now a longstanding experience in the study of the innate immune responses to influenza
virus and P. aeruginosa. He published 82 articles (H-index: 32) and contributed to two patents and several grants focused on lung infection (JPI-AMR, French cystic fibrosis foundation,…). He also co-founded Cynbiose Respiratory, a CRO, preclinical- stage company specialized in experimental models in the respiratory field.