Chemical Biology, Immunology

Chemistry & Biology, Modeling & Immunology for Therapy

+33 1 76 53 42 56 room R271

Laboratoire de Chimie et Biochimie pharmacologiques et toxicologiques (LCBPT) – CNRS UMR 8601
Université Paris Descartes
45 Rue des Saints Pères
75270 Paris Cedex 06
France

Curriculum Vitae

• Academic degrees and management

2019       Scientific Founder of Ermium Therapeutics (www.ermium.com)
2018       Training for start-up creation at DeepTech Founders, Ministère de la Recherche, BPI France
2018       Direction of the Molecular Biology Plateform of Faculté Biomédicale des Saints-Pères (Cyto2BM)
2016       Founder and scientific direction of Cytometry and sorting platform, Faculté des Saints-Pères
2015       Co-Founder of SantImmune Foundation, Université Paris Descartes
2013       Member of scientific board of CICB, Faculté des Saints-Pères
2013       DR2 position, commission 27 CNRS
2012      Creation and direction of CBMIT, CNRS UMR 8601, Faculté des Saints-Pères
2008      Habilitation to direct research (HDR), Université Paris Descartes
2006      CR1 position, CNRS UMR 8147, Hôpital Necker, Paris
2001      Postdoctoral fellowship (5years) EIB, NCI, NIH, Bethesda, USA, Dr. Gene Shearer
2001      PhD in Onco-immunology, GIMAP-INSERM Université Jean Monnet

• Honors and awards

2019      National award: Concours national de l’innovation I-Lab, BPI-France, Ministère de la recherche
2012       CNRS award for scientific excellence (PES)
2007       Special lecture for the 25^th Anniversary of the discovery of HIV, NIAID-NIH
2006       Special grant “Urgence Postdoc” Fondation pour la Recherche Médicale (FRM)
2005       Norman P. Salzman Memorial Award in Virology, NIH, SAIC, FDA, USA
2005       NIH Young Scientist Cash Award, USA
2002       IATAP grant for HIV research, NIH, USA
2001       Fogarty postdoctoral fellowship grant, NIH, Bethesda, USA

• Valorization-patents

2019      Patent: Imidazoline derivatives as CXCR4 modulators, JP. Herbeuval, N. Smith, N. Pietrancosta, M, Rodero, N. Bekaddour, dépôt à l’office européen des brevets, SATT-IdF innov . # EP19305409.1110 Mars 2019
2017      Maturation contracts (SATT-idf innov, 2016 and 2018)
2017      Patent: High throughput test of cytotoxic activity of NK cells by bioluminescence. PO Vidalain, JP Herbeuval, S. Hayek, N. Bekkadour. SATT-IdF innov. # S2016120202
2016      Patent: CXCR4-binding compound for increasing interferon level in the prevention or treatment of diseases needing IFN boost, JP. Herbeuval, N. Smith, N. Pietrancosta, # EP16305736.
2016      Patent: CXCR4 receptor-binding compound for decreasing interferon (IFN) level in the prevention or treatment of interféronopathies, J-P. Herbeuval, N. Smith, N. Pietrancosta, # EP16305735.
2006      Patent: Methods and composition for diagnosing AIDS and other diseases and conditions involving immune system activation. J-P. Herbeuval, GM Shearer, # WO/2005/114187

• Start-up creation Ermium Therapeutics

Ermium Therapeutics (www.ermium.com) is a biotech company developing innovative therapies for auto-immune diseases, based on a breakthrough discovery showing that CXCR4 is a master regulator of inflammation. Ermium Therapeutics was founded in June 2019 by Jean-Philippe HERBEUVAL, Kurma Partners, Idinvest Partners, Domain Therapeutics and Erganeo. The company is based in Paris and has signed a worldwide exclusive license agreement on intellectual property from CNRS and University Paris Descartes (France) through an agreement with Erganeo, which supported the maturation of the project in an academic setting. In addition, Ermium Therapeutics recently won the innovation i-Lab 2019 award from the French Ministry of Research and Higher Education.

• Creation and management of the team CBMIT

In September 2012, I created with Pr. M. Etheve-Quelquejeu a new team “Chemistry Biology Modeling and Immunotherapy” (CBMIT) within the CNRS-UMR8601. Development of interdisciplinary projects integrating chemical synthesis, molecular modeling and high throughput screening. Study of IFN regulation and to develop new therapeutic strategies for modulating immune. Team composed by 7 permanent researchers: 1 PR1 Paris Descartes, 2 DR2 CNRS, 1 DR2 INSERM, 3 MCU Paris Descartes. The past 2 years the attractiveness of the team allowed the recruitment of researchers in chemistry, molecular modeling and virology. PO Vidalain (from Institut Pasteur) joined the team in 2015 and obtained his DR2 position at CBMIT, N. Pietrancsota (CR1, HDR), R. Alves-de-Sousa (IE, PhD), A. Mellet (MCU, HDR) and M. Rodero (PhD, HDR) joined the team between 2016 and 2018. Since 2012 the CBMIT member published papers in various domain including: immunology, virology, oncology, chemistry, multidisciplinary (Immunity, Nat Com, Angew Chem, Cell report, Plos Pathogens…)

• Creation of SantImmune Foundation

In February 2015, we created with Pierre-Olivier Vidalain (DR2, Bronze medal of CNRS), the SantImmune Foundation hosted by Paris Descartes Foundation. SantImmune is financing immunotherapy drug development.
http://fondation.parisdescartes.fr/santimmune

• Subvention and fundraising

2018       Maturation contract by SATT-idf Innov (PI, 140,000 € 2 years), CBMIT, CNRS UMR8601
2017       ANRS PhD fellowship (N. Bekkadour, 3 years), CBMIT, CNRS UMR8601
2017       ANRS grant (PI, 60,000 €, 2 years), CBMIT, CNRS UMR8601
2016       Maturation contract by SATT-idf Innov (PI, 150,000 € 2 years), CBMIT, CNRS UMR8601
2016       Fundraising SantImmune Foundation Paris Descartes (55,000€), CNRS UMR8601
2016       ANRS postdoctoral grant (N. Smith, 1 year), CBMIT, CNRS UMR8601
2015       ANRS grant in collaboration with B. Manoury (PI, 170,000€, 3 years), CBMIT, CNRS UMR8601
2015       ANR grant, PI- PO Vidalain (280,000 €, 3years), CBMIT, CNRS UMR8601
2015       ANRS grant, PI- PO Vidalain (30,000 € 1year), CBMIT, CNRS UMR8601
2012       ANRS grant (PI, 280,000 €), CBMIT, CNRS UMR8601
2012       Sidaction grant (PI, 33,000 €, 1 year), CBMIT, CNRS UMR8601
2012       Grant CAPES-COFECUB for international collaboration (3 years), CBMIT, CNRS UMR8601
2011       International grant cooperation CNRS-Brazil, (PI, 1 year), CNRS UMR8147
2007       ANRS grant (PI, 185,000 €, 3years), CNRS UMR8147, Hôpital Necker
2005       NIH Intramural AIDS Antiviral Program Instrument Award (PI, 300,000 $, 1 year)
2004       NIH Intramural AIDS Antiviral Program Instrument Award (PI, 250,000 $, 1 year)
2003       NIH Intramural AIDS Antiviral Program Research Award, (PI, 200,000 $, 1 year)
2002       AIDS Vaccine Program, NCI, Frederick (PI, 15,000 $, 1 year)

• National and International expertise

-Grant scientific reviewing: R0-1 NIH, USA (2013, 2014), Wellcome Trust, London (2014), Sidaction (2017), ANR (2013), Ligue contre le cancer (2011, 2012)
-Journal reviewing: Nature Medicine, Nature Communications, Plos Pathogens, eLife, Journal of Immunology…
-International collaborations: Marcus Altfeld (Ragon Institute, Harvard med school, USA), Andreas Wack (Francis Crick Institute, UK), Jan Münch and Frank Kirchhoff (Ulm University, Germany), Claire Kubelka (Fiocruz, Rio de Janeiro).

• PhD Students/Postdocs Management

– Mathieu Rodero, postdoctoral position at CBMIT (2018)

– Mirja Harms, PhD in co-management with Pr. Jan Munch, Ulm University, Germany (2017-220).

– Nassima Bekkadour, M1 and 2 and PhD at CBMIT, ANRS PhD grant (2017-2020).

– Clarissa Nascimiento Postdoctoral fellowship ANRS grant (2015-2018), CBMIT and Hôpital Necker.

– Nikaïa Smith, Master 2, PhD (MRT fellowship), and Postdoc at CBMIT (2012-2017). Award in Pharmacy by the Chancellerie des Universités de Paris, 17 publications (Nat Com, J Med Chem, Cancer Lett.). N. Smith was awarded by an EMBO fellowship at Ulm University in Pr Frank Kirchhoff, Germany.

– Mariana Gandini, PhD in co-direction at CBMIT with the immunology-virology laboratory (Fiocruz, Rio, Brésil) (2011-2014), PI position at Fiocruz, Rio-de Janeiro, Brazil (2015).

– Kawthar Machmach, PhD in codirection with the Laboratory of Immunovirology, Universitad Virgen del Rocio, Spain (2009-2012). 8 Publications, Postdoctoral position at Université de Montreal, Canada.

– Lucie Barlu, Doctoral School GC2iD (MRT fellowship), Université Paris 11, (Laureate of the Bourse l’Oréal-UNESCO- Académie des Sciences 2010), 5 publications, Postdoctoral position at Ragon Institute Harvard Med School, USA.

– Renaud Colisson, ANRS Postdoctoral fellowship grant (2009-2010), Hôpital Necker.

• Member of jury

– Reviewer of 8 PhD thesis (Institut Pasteur, ENS Lyon, Institut Currie..) and examiner of 14 PhD thesis.
– President of HDR of Matieu Rodero (Institut Imagine) and Darragh Duffy (Institut Pasteur).

• Teaching

2017-2018  Immunolgy and IFN regulation, Master BioMedical Engineering (BME), Faculté des Saints-Pères.
2011-2012  Immunology, License at  ESTBA, Paris.
1998-2000  Assistant professor (94h/year) in Immunology, Faculty of Science, Université Jean-Monnet.
1998-2000  Endocrinology and immunology (40h/year), International School of Oestopathy, Saint-Etienne.

• Research fields

1998-2001   Onco-immunology, study of macrophages IFN and TRAIL response during anti-tumor response.
2001-2006   Innate immune response and IFN regulation in viral infection (HIV, Dengue, HTLV-1, Flu).
2012-2020   Interface chemistry-biology, in silico modeling, and anti-IFN drug development for immunotherapy.
2018-2020 Immunologic study, drug development for immotherapy in autoimmune diseases. Collaborative projects and patient cohorts with interferonopathies (JDM, SLE, STING) and inflammatory disease.

MultiMedia

1. Research Highlights in Nature Reviews Rheumatology: Hitting the right spot on CXCR4, August 2019 https://www.nature.com/articles/s41584-019-0287-6
2. Alerte presse CNRS-INC-INSB: Une molécule prometteuse pour traiter le lupus (Septembre 2019) http://www.inc.cnrs.fr/fr/cnrsinfo/une-molecule-prometteuse-pour-traiter-le-lupus
3. Biocentury : CXCR4 ligands as lupus drugs, July 2019 https://www.biocentury.com/archives?rsid=5473e895-9495-4485-a606-b3a2ebe3c4ec&kwb=herbeuval&st=general
4. Manuel scolaire de 3ème, édition Nathan 2019: les cellules productrices d’IFN
5. Le Monde- Sens et Santé : Vers de nouvelles molécules anti-allergiques. Mars-Avril 2018
6. France 2: impact du cerveau sur nos défenses immunitaires (1/09/2017). https://www.youtube.com/watch?v=bUYqQDz2I2g
7. CNRS Le journal : Interview à l’occasion de la conférence sur le SIDA, IAS Paris 2017. https://lejournal.cnrs.fr/articles/contre-le-vih-la-recherche-sur-tous-les-fronts
8. Libération: http://www.liberation.fr/debats/2017/05/14/pourquoi-les-humeurs-jouent-sur-notre-sante_1569471
9. CNRS Le journal: Pourquoi les humeurs jouent sur notre santé.https://lejournal.cnrs.fr/billets/pourquoi-les-humeurs-jouent-sur-notre-sante
10. France Inter, “Le club de la tête au carrée”, 10 Février 2017 (https://www.franceinter.fr/emissions/la-tete-au-carre/la-tete-au-carre-10-fevrier-2017)
11. Sciences et Avenir : Comment dépression et allergies favorisent les infections virales, 9 Février 2017 (https://www.sciencesetavenir.fr/sante/cerveau-et-psy/comment-depression-et-allergies-favorisent-les-infections-virales_110431)
12. The conversation : Allergies: comment une surproduction d’histamine lors d’épisodes allergiques nous sensibilise aux infections virales, 1 Mars 2017 (article en français et en anglais)
13. Fondation pour l’innovation politique : http://www.anthropotechnie.com/pourquoi-les-humeurs-jouent-sur-notre-sante/
14. Labnaut : les allergies et leur conséquence sur nos défenses immunitaires, mars 2017
15. Le Huffington Post : Comment les allergies affaiblissent nos défenses immunitaires, 9 Février 2017
16. Le quotidien du médecin : Allergies : comment l’histamine bloque la réponse antivirale, le 9 Février 2017
17. Alerte presse CNRS-INSB − Dépression, allergies : comment ces maladies diminuent nos défenses immunitaires et favorisent les infections virales. 6 février 2017
18. TV5 Monde : « Les 24h chrono de l’international : focus sur Washington DC », Interview en plateau du 17 Janvier 2017

Recent publications

1. Maarifi G, Smith N, Maillet S, Moncorgé O, Chamontin C, Edouard J, F Sohm, Blanchet F, Herbeuval JP, Lutfalla G, Levraud JP, Arhel N and Nisole S. TRIM8 is required for virus-induced IFN response in human plasmacytoid dendritic cells. Science advances, 20 Nov 2019:Vol.5,no.11, eaax3511DOI: 10.1126/sciadv.aax3511.
2. Hayek S, Pietrancosta N, Hovhannisyan AA, Alves de Sousa R, Bekaddour N, Ermellino L, Tramontano E, Arnould S, Sardet C, Dairou J, Diaz O, Lotteau V, Nisole S, Melikyan G, HerbeuvalJP, Vidalain PO. Cerpegin-derived furo[3,4-c]pyridine-3,4(1H,5H)-diones enhance cellular response to interferons by de novo pyrimidine biosynthesis inhibition. Eur J Med Chem. 2019 Nov 6:
3. Gitiaux C, Bondet V, Bekaddour N, Nusbaum P, Hubas A, Melki I, Bodemer C, Quartier P, Desguerre I, Crow YJ, Herbeuval J-P, Duffy D, Bader Meunier B, Rodero MP. Inhibition of IFNα secretion in cells from patients with juvenile dermatomyositis under TBK1 inhibitor treatment revealed by single-molecular assay technology. Rheumatology (Oxford). 2019 Oct 30
4. Smith N, Rodero M P, Bekaddour N, Bondet V, Ruiz-Blanco Y B., Harms M, Mayer B, Badder-Meunier B, Quartier P, Bodemer C, Baudouin V, Dieudonné Y, Kirchhoff F, Sanchez Garcia E, Charbit B, Leboulanger N, Jahrsdörfer B, Richard Y, Korganow AS, Münch J, Nisole S, Duffy D, Herbeuval JP. Control of TLR7-mediated type I IFN signaling in pDCs through CXCR4 engagement – a new target for Lupus treatment. Science Advances, 2019 Jul 10;5(7):eaav9019. doi: 10.1126/sciadv.aav9019
5. HayekS, Bekaddour N, BessonL, Alves de SousaR, PietrancostaN, Viel S, Smith N, Jacob Y, Nisole S, MandalR, Wishart DS, WalzerT, Herbeuval JP, Vidalain PO. Identification of Primary Natural Killer Cell Modulators by Chemical Library Screening with a Luciferase Based Functional Assay. SLAS Discovery, 2019 Jan:. doi: 10.1177/2472555218797078
6. Sinigaglia L, Gracias S, Décembre E, Fritz M, Bruni D, Smith N, HerbeuvalJP, Martin A, Dreux M, Tangy F, Jouvenet N. Yellow fever vaccine-infected cells stimulate plasmacytoid dendritic cells to produce IFN type-I and -III independently of viral particleand exosome production. Sci Rep. 2018 Jul 18;8(1):10889. PMID: 30022130
7. Müller JA, Harms M, Krüger F, Groß R, Joas S, Hayn M, Dietz AN, Lippold S, von Einem J, Schubert A, Michel M, Mayer B, Cortese M, Jang KS, Sandi-Monroy N, Deniz M, Ebner F, Vapalahti O, Otto M, Bartenschlager R, Herbeuval JP, Schmidt-Chanasit J, Roan NR, Münch J. Semen inhibits Zika virus infection of cells and tissues from the anogenital region. Nat Commun. 2018 Jun 7;9(1):2207. PMID: 29880824
8. HayekS, PietrancostaN, Alves de SousaR, BaroukiR, Herbeuval JP, Vidalain PO. Pollution chimique et immunité innée antivirale : des liaisons dangereuses ? Virologie, Janvier-Février 2018, volume 22 numéro 1
9. Smith N and Herbeuval JP. Mechanisms underlying plasmacytoid dendritic cell regulation by HIV. Future Virology, 2017 August 25. DOI: 10.2217/fvl-2017-0052.
10. Smith N, Pietrancosta N, Herbeuval JP. CXCR4: nouveau régulateur de l’immunité innée. Médecine Sciences, 2017 Aug-Sep;33(8-9):711-713. PMID: 28945553
11. 10. Khiar S, Lucas-Hourani M, Nisole S, Smith N, Helynck O, Bourgine M, Ruffié C, Herbeuval JP, Munier-Lehmann H, Tangy F, Vidalain PO. Identification of a small molecule that primes the type I interferon response to cytosolic DNA. Sci Rep. 2017 May 31;7(1):2561. PMID: 28566766
12. Allam A, Maigre L, Vergalli J, Dumont E, Cinquin B, Alves de Sousa R, Pajovic J, Pinet E, Smith N, Herbeuval JP, Réfrégiers M, Artaud I, Pagès JM. Microspectrofluorimetry to dissect the permeation of ceftazidime in Gram-negative bacteria. Sci Rep. 2017 Apr 20;7(1):986. PMID: 28428543
13. Müller J, Harms M, Schubert A, Mayer B, Jansen S, Herbeuval JP, Michel D, Mertens T, Vapalahti O, Schmidt-Chanasit J, Münch J. Development of a high-throughput colorimetric Zika virus infection assay. Medical Microbiology and Immunology, 2017 Apr;206(2):175-185. PMID: 28176006
14. 13. Smith N, Pietrancosta N, Dutrieux J, Davidson S, Chaveau L, Cuttolo P, Dy M, Scott-Algara D, Manoury B, McCort I, Dutroux T, Bachelerie F, Schwartz O, Wack A, Nisole S, Herbeuval JP. Natural amines inhibit activation of human pDC through CXCR4 engagement. Nat Commun. 2017 Feb 9;8:14253. PMID: 28181493
15. Smith N, Vidalain PO, Nisole S, Herbeuval JP. An efficient method for gene silencing in human primary plasmacytoid dendritic cells: silencing of the TLR7/IRF-7 pathway as a proof of concept. Sci Rep. 2016 Jul 14;6:29891. PMID: 27412723
16. Saïdi H, Bras M, Formaglio P, Melki MT, Charbit B, Herbeuval JP, Gougeon ML. HMGB1 Is Involved in IFN-α and TRAIL by HIV-1-Exposed pDC: Impact of the Crosstalk with NK Cells. PLoS Pathog. 2016 Feb 12;12(2):e1005407. PMID: 26871575
17. Borhis G, Burelout C, Chaoul N, Smith N, Goujard C, Meyer L, Paul S, Saoudin H, Hosmalin A, Gilbert C, Herbeuval JP, Richard Y. PDC and mDC differently contribute to B-cell-activating factor belonging to the TNF superfamily overexpression during primary HIV infection. AIDS. 2016 Jan 28;30(3):365-76. PMID: 26558721