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Alain R. Thierry

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Alain Thierry (born 21 October 1959) is a French geneticist and cancer researcher. He specializes in the clinical applications of circulating DNA analysis, notably in cancer care management. He is currently Director of Research at the INSERM's Cancer Research Institute in Montpellier, France.

Education

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Thierry obtained his primary degree in Cellular and Molecular Biology (MSc) at the University of Clermont-Ferrand[1] in France in 1982. In 1986 he completed his PhD in Biochemistry, Cellular and Molecular Pharmacology at the University of Montpellier II.[2] The following year he was awarded the Certificat d’Etudes Supérieures (CES) in Human Biology in Clinical and Experimental Oncology, from the Paris-Sud Faculty of Medicine.

Career

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Thierry began his career in the US as a Postdoctoral Fellow (1988–92) at the Lombardi Cancer Centre in the Georgetown University Medical Centre (Washington DC), going on to work there as Adjunct Assistant Professor from 1992 to 1994. From 1992 to 1996 he was also a Visiting Scientist at the Laboratory of Tumor Cell Biology at the National Institutes of Health in Bethesda, where he worked with Dr. Robert C. Gallo, the laboratory's Director.

Returning to France, from 1997 to 2000 he served as Scientific Director at the Biovector Therapeutics company. From 2001 to 2007 he was Associate Professor[3] at Montpellier University's Faculty of Sciences. Since 2008, he has been the Senior Investigator and Director of Research at the INSERM's Cancer Research Institute of Montpellier (IRCM).[4]

He is the principal founder of the MedinCell and DiaDx biotech companies in France. The latter develops liquid biopsy solutions in oncology.

Research

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Thierry specializes in the clinical application of liquid biopsy that exploits circulating DNA as a biomarker, notably in cancer management care. He has been the principal investigator in numerous discoveries in drug delivery innovation and application in oncology.

It was during his period at Georgetown that he showed the circumvention of multi-drug resistance in tumors through drug delivery.[5] There, he also developed his expertise in synthetic DNA complex formation, notably regarding its use for in vivo gene therapy. He built on this work at the US National Cancer Institute,[6] developing gene therapy for cancer and HIV,[7][8] in particular the first long term expression of a transgene by systemic administration with a synthetic delivery system.[9]

While at the University of Montpellier, he worked first on the pharmacokinetics of therapeutic vectorized HIV antisense oligonucleotides in primates (2002).[10] He then went on to demonstrate the biomimetic supramolecular auto-organization of DNA in a synthetic complex (2006).[11]

Since 2006, Thierry has focused increasingly on clinical and basic research into the role of circulating DNA (cirDNA), and on its diagnostic potential in oncology. In this area, he has worked notably on: the detection of mutations following targeted therapy; the follow-up of CRC patients; and the prognostic power of cirDNA, with potential application in a universal cancer screening test. He has also worked towards the development of methods which support personalized medicine.

In 2009, his team developed an animal model to specifically quantify the different origins of cirDNA / circulating tumor DNA, and demonstrated the importance of short cirDNA fragment detection for high specificity and sensitivity in cirDNA analysis.[12][13] That observation enabled dominant IP and the design of the IntPlex test, a multimarker quantitative analysis of cirDNA that also enables the detection of mutations.[14]

In 2014, Thierry coordinated the first prospective blinded multicenter study to offer clinical validation of plasma analysis in the detection of mutations in oncology, and to demonstrate the clinical utility of cirDNA analysis in digestive oncology.[15][16][17]

His team has also engaged in sustained basic research programs on cirDNA structure and functions.[18] Key discoveries in this area include the demonstration of the presence in blood of circulating functional cell-free mitochondria (2020),[19] and the demonstration that most cirDNA derives from neutrophil extracellular traps (NETs), either in the presence of invasive microorganisms or of cancer.[20] In a related discovery, they were amongst the first (in April 2020) to suggest NETs as a key player in COVID-19 pathogenesis (2020)[21] and have shown long COVID-19 (COVID post-acute phase syndrome) to be an effect of the persistence of the production of NETs and auto-antibodies.[22] Recently (2022), they have demonstrated cirDNA association with NETs production in cancer and lupus.[20]

Most recently, Thierry has pioneered work on cirDNA fragmentation, proposing potential solutions towards cancer screening through the use of fragmentomics.[23] This builds on earlier work (2011) on the fragmentation levels of cancer patient cirDNA.[24][13]

According to Google Scholar, he has an h-index of 45.[25]

Awards and honors

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References

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  1. ^ "Université Clermont Auvergne". Université Clermont Auvergne. Retrieved 2023-05-04.
  2. ^ "Université de Montpellier". umontpellier.fr (in French). Retrieved 2023-05-04.
  3. ^ "Identification of Personnel in Higher Education and Research". 2020-10-18.
  4. ^ "CV Alain R. Thierry - Institut de Recherche en Cancérologie de Montpellier". www.ircm.fr. Retrieved 2023-05-04.
  5. ^ Thierry, Alain R.; Vigé, Dominique; Coughlin, Steven S.; Belli, James A.; Dritschilo, Anatoly; Rahman, Aquilur (April 1993). "Modulation of doxorubicin resistance in multidrug-resistant cells by liposomes". The FASEB Journal. 7 (6): 572–579. doi:10.1096/fasebj.7.6.8097173. ISSN 0892-6638. PMID 8097173. S2CID 25142393.
  6. ^ "Kaposi's sarcoma will be initial focus of NCI's Gallo's new outside Institute of Human Virology". pink.pharmaintelligence.informa.com. 5 June 1995.
  7. ^ https://irp.nih.gov/system/files/media/file/2022-01/NIH_catalyst_v06i1_1998-Jan-Feb.pdf
  8. ^ Lunardi-lskandar, Yanto; Bryant, Joseph L.; Zeman, Robert A.; Lam, Victor H.; Samaniego, Felipe; Besnier, Jacques M.; Hermans, Philippe; Thierry, Alain R.; Gill, Parkash; Gallo, Robert C. (May 1995). "Tumorigenesis and metastasis of neoplastic Kaposi's sarcoma cell line in immunodeficient mice blocked by a human pregnancy hormone". Nature. 375 (6526): 64–68. Bibcode:1995Natur.375...64L. doi:10.1038/375064a0. ISSN 1476-4687. PMID 7723844. S2CID 4352863.
  9. ^ Thierry, A R; Lunardi-Iskandar, Y; Bryant, J L; Rabinovich, P; Gallo, R C; Mahan, L C (1995-10-10). "Systemic gene therapy: biodistribution and long-term expression of a transgene in mice". Proceedings of the National Academy of Sciences. 92 (21): 9742–9746. Bibcode:1995PNAS...92.9742T. doi:10.1073/pnas.92.21.9742. ISSN 0027-8424. PMC 40878. PMID 7568209.
  10. ^ Tavitian, Bertrand; Marzabal, Stéphane; Boutet, Valérie; Kühnast, Bertrand; Terrazzino, Salvatore; Moynier, Marinette; Dollé, Frédéric; Deverre, Jean Robert; Thierry, Alain R. (2002-04-01). "Characterization of a Synthetic Anionic Vector for Oligonucleotide Delivery Using in Vivo Whole Body Dynamic Imaging". Pharmaceutical Research. 19 (4): 367–376. doi:10.1023/A:1015133205457. ISSN 1573-904X. PMID 12033366. S2CID 24269784.
  11. ^ Schmutz, M.; Durand, D.; Debin, A.; Palvadeau, Y.; Etienne, A.; Thierry, A. R. (1999-10-26). "DNA packing in stable lipid complexes designed for gene transfer imitates DNA compaction in bacteriophage". Proceedings of the National Academy of Sciences. 96 (22): 12293–12298. Bibcode:1999PNAS...9612293S. doi:10.1073/pnas.96.22.12293. ISSN 0027-8424. PMC 22910. PMID 10535915.
  12. ^ Thierry, Alain R.; Mouliere, Florent; Gongora, Celine; Ollier, Jeremy; Robert, Bruno; Ychou, Marc; Del Rio, Maguy; Molina, Franck (2010-10-01). "Origin and quantification of circulating DNA in mice with human colorectal cancer xenografts". Nucleic Acids Research. 38 (18): 6159–6175. doi:10.1093/nar/gkq421. ISSN 0305-1048. PMC 2952865. PMID 20494973.
  13. ^ a b Mouliere, Florent; Robert, Bruno; Arnau Peyrotte, Erika; Del Rio, Maguy; Ychou, Marc; Molina, Franck; Gongora, Celine; Thierry, Alain R. (2011-09-06). Lee, Terence (ed.). "High Fragmentation Characterizes Tumour-Derived Circulating DNA". PLOS ONE. 6 (9): e23418. Bibcode:2011PLoSO...623418M. doi:10.1371/journal.pone.0023418. ISSN 1932-6203. PMC 3167805. PMID 21909401.
  14. ^ Thierry, Alain R. (2016), Luthra, Rajyalakshmi; Singh, Rajesh R.; Patel, Keyur P. (eds.), "A Targeted Q-PCR-Based Method for Point Mutation Testing by Analyzing Circulating DNA for Cancer Management Care", Clinical Applications of PCR, Methods in Molecular Biology, vol. 1392, New York, NY: Springer New York, pp. 1–16, doi:10.1007/978-1-4939-3360-0_1, ISBN 978-1-4939-3358-7, PMID 26843041, retrieved 2023-05-04
  15. ^ Thierry, Alain R; Mouliere, Florent; El Messaoudi, Safia; Mollevi, Caroline; Lopez-Crapez, Evelyne; Rolet, Fanny; Gillet, Brigitte; Gongora, Celine; Dechelotte, Pierre; Robert, Bruno; Del Rio, Maguy; Lamy, Pierre-Jean; Bibeau, Frederic; Nouaille, Michelle; Loriot, Virginie (April 2014). "Clinical validation of the detection of KRAS and BRAF mutations from circulating tumor DNA". Nature Medicine. 20 (4): 430–435. doi:10.1038/nm.3511. ISSN 1078-8956. PMID 24658074. S2CID 205392847.
  16. ^ "A blood test to detect tumor-derived mutations | DiaDx | Liquid Biopsy For Personalised Medicine In Oncology". DiaDx. Retrieved 2023-05-04.
  17. ^ Thierry, A.R.; El Messaoudi, S.; Mollevi, C.; Raoul, J.L.; Guimbaud, R.; Pezet, D.; Artru, P.; Assenat, E.; Borg, C.; Mathonnet, M.; De La Fouchardière, C.; Bouché, O.; Gavoille, C.; Fiess, C.; Auzemery, B. (September 2017). "Clinical utility of circulating DNA analysis for rapid detection of actionable mutations to select metastatic colorectal patients for anti-EGFR treatment". Annals of Oncology. 28 (9): 2149–2159. doi:10.1093/annonc/mdx330. ISSN 0923-7534. PMID 28911069.
  18. ^ Thierry, A. R.; El Messaoudi, S.; Gahan, P. B.; Anker, P.; Stroun, M. (September 2016). "Origins, structures, and functions of circulating DNA in oncology". Cancer and Metastasis Reviews. 35 (3): 347–376. doi:10.1007/s10555-016-9629-x. ISSN 0167-7659. PMC 5035665. PMID 27392603.
  19. ^ Al Amir Dache, Zahra; Otandault, Amaëlle; Tanos, Rita; Pastor, Brice; Meddeb, Romain; Sanchez, Cynthia; Arena, Giuseppe; Lasorsa, Laurence; Bennett, Andrew; Grange, Thierry; El Messaoudi, Safia; Mazard, Thibault; Prevostel, Corinne; Thierry, Alain R. (March 2020). "Blood contains circulating cell-free respiratory competent mitochondria". The FASEB Journal. 34 (3): 3616–3630. doi:10.1096/fj.201901917RR. ISSN 0892-6638. PMID 31957088. S2CID 210831342.
  20. ^ a b Pisareva, Ekaterina; Mihalovičová, Lucia; Pastor, Brice; Kudriavtsev, Andrei; Mirandola, Alexia; Mazard, Thibault; Badiou, Stephanie; Maus, Ulrich; Ostermann, Lena; Weinmann-Menke, Julia; Neuberger, Elmo W. I.; Simon, Perikles; Thierry, Alain R. (2022-11-28). "Neutrophil extracellular traps have auto-catabolic activity and produce mononucleosome-associated circulating DNA". Genome Medicine. 14 (1): 135. doi:10.1186/s13073-022-01125-8. ISSN 1756-994X. PMC 9702877. PMID 36443816.
  21. ^ Thierry, Alain; Roch, Benoit (2020-04-15). "NETs By-products and Extracellular DNA May Play a Key Role in COVID-19 Pathogenesis: Incidence on Patient Monitoring and Therapy". doi:10.20944/preprints202004.0238.v1. {{cite journal}}: Cite journal requires |journal= (help)
  22. ^ Pisareva, Ekaterina; Badiou, Stephanie; Mihalovičová, Lucia; Mirandola, Alexia; Pastor, Brice; Kudriavtsev, Andrei; Berger, Marie; Roubille, Camille; Fesler, Pierre; Klouche, Kada; Cristol, Jean-Paul; Thierry, Alain R. (January 2023). "Persistence of neutrophil extracellular traps and anticardiolipin auto-antibodies in post-acute phase COVID-19 patients". Journal of Medical Virology. 95 (1): e28209. doi:10.1002/jmv.28209. ISSN 0146-6615. PMC 9874393. PMID 36226380.
  23. ^ Thierry, A.R. (January 2023). "Circulating DNA fragmentomics and cancer screening". Cell Genomics. 3 (1): 100242. doi:10.1016/j.xgen.2022.100242. PMC 9903826. PMID 36777187.
  24. ^ Sanchez, Cynthia; Roch, Benoit; Mazard, Thibault; Blache, Philippe; Dache, Zahra Al Amir; Pastor, Brice; Pisareva, Ekaterina; Tanos, Rita; Thierry, Alain R. (2021-04-08). "Circulating nuclear DNA structural features, origins, and complete size profile revealed by fragmentomics". JCI Insight. 6 (7). doi:10.1172/jci.insight.144561. ISSN 0021-9738. PMC 8119211. PMID 33571170.
  25. ^ "alain THIERRY". scholar.google.fr. Retrieved 2023-05-04.
  26. ^ "Cinq chercheuses et chercheurs reçoivent les Prix 2021 de l'Innovation "Montpellier Université d'Excellence" - Université de Montpellier". umontpellier.fr (in French). 16 December 2021. Retrieved 2023-05-04.
  27. ^ "La Fondation pour l'Innovation Thérapeutique Béatrice Denys: récompenses 2016".
  28. ^ "Prix de l'Innovation Therapeutique Beatrice Denys". 24 June 2016.
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