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Thomas Baumert

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Thomas Baumert (born May 20, 1965) is a German-French physician-scientist and entrepreneur. He is a Professor of Medicine at the University of Strasbourg and the Chief of the Gastroenterology-Hepatology Service at the Strasbourg University Hospitals [fr]. He is the founder of Alentis Therapeutics, a clinical-stage biotech company in Basel. He works on the basic, translational, and clinical investigation of liver disease and cancer.

Thomas F. Baumert
Alma materUniversity of Freiburg, University of Heidelberg
Born20 May 1965 in Berlin, Germany
NationalityGerman and French
FamilyMarried, 2 children

Baumert and his teams have discovered and developed novel strategies to treat fibrosis and cancer. He has published more than 400 scientific articles including in The New England Journal of Medicine, Cell, Nature, and Science Translational Medicine. His work has been recognized by several awards and honors, including the Galien Prize and the Inserm Research Award.

Education

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Baumert studied medicine at the Freiburg and Heidelberg universities, the University of Chicago, and at the Baylor College of Medicine. On completing a doctoral thesis at the German Cancer Research Center (DKFZ) in Heidelberg, and a medicine internship at the Ludwig Maximilians University (LMU) in Munich, Baumert received his MD degree from the Heidelberg University. He then moved to America to become a fellow at Harvard Medical School. He returned to Germany to join the Department of Medicine at the University Hospital in Freiburg, where he qualified as a board-certified internist and gastroenterologist. He later moved to Strasbourg in France, where he became a full Professor of Medicine at the University of Strasbourg where he created a new Inserm research unit, and started a research program in translational hepatology.

Scientific contributions

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Scientific career

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Thomas Baumert began his scientific career as an MD student in the laboratory of Dietrich Keppler, MD at the German Cancer Research Center (DKFZ). At the DKFZ, he worked out how leukotrienes that are degraded in the liver contribute to alcoholic liver disease.[1] Following a clinical internship at the University of Munich Medical Center, he completed a postdoctoral fellowship studying viral liver disease where he worked out how defined acquired mutations in the genome of hepatitis B virus contribute to liver disease[2] and discovered and developed a vaccine candidate to prevent hepatitis C virus infection.[3] Subsequently, he joined the University Hospital Freiburg under the leadership of Hubert E. Blum, MD where he created an EU-funded research group focusing on the viral pathogenesis of liver disease.

During his tenure at Inserm and at the University of Strasbourg, he has identified key host liver factors for hepatitis viruses as drivers and targets for virus-induced liver disease and cancer,[4][5][6][7][8][9] and the explained the crucial role of virus-specific antibodies for clearance and control of hepatitis C virus infection.[10] He was trusted with the organization and hosting of the 22nd international symposium on hepatitis C virus and related viruses, in Strasbourg in 2015.[11]

Following a sabbatical at the Broad Institute, the Massachusetts General Hospital and the Harvard Medical School in 2014, he built a new program on the investigation of the cell circuits of liver disease and cancer, using novel patient-derived models combined with scRNASeq and integrative computational analyses. Using perturbation studies combined with integrative systems biology he and his team showed that chronic viral or metabolic liver injury results in epigenetic footprints in patients with advanced liver disease driving and predicting liver fibrosis progression and cancer risk.[12][13]

Using patient-derived liver models[14] combined with scRNASeq and the first human liver single cell atlas established by his team with external collaborators[15] Baumert and his team uncovered novel approaches to treat fibrosis and prevent cancer, which led to his discovery of the cell surface protein Claudin-1 as a previously unknown mediator and therapeutic target for fibrosis and cancer across organs. Using hepatitis C virus entering cancer cells as a model system, he discovered and developed a unique panel monoclonal antibodies targeting exposed Claudin-1 on epithelial cells[7][16] to treat fibrosis across organs and cancer.[17] Baumert and his team showed that therapeutic antibodies targeting exposed Claudin-1 on the cancer cell surface efficiently inhibit liver tumor growth by changing cell plasticity, suppressing carcinogenic signaling and reprogramming the tumor immune microenvironment.[18]

Research programs

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His research programs have received support from European and international funding bodies including the European Research Council (ERC), the German, and French Research Foundations and the US National Institutes of Health including NCI, NIDDK and NIAID. He was awarded several ERC Advanced Grants (AdG)[19][20] and Proof of Concept Grants (PoC).[21]

Baumert has led over 50 research programs in liver disease and cancer and mentored 40+ PhD and MD/PhD students, 50+ fellows, and 20+ faculty members. He is leading the RHU DELIVER program – a consortium gathering academia, hospitals, and pharmaceutical companies funded by the French Research Agency ANR to improve the care of patients with advanced liver disease.[22]

Entrepreneurship

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The translational and commercial impact of his research is reflected by more than 25 patent applications for novel therapeutic approaches in the last ten years, leading to multiple partnerships and collaborations with pharmaceutical industries and the creation of biotech companies in France and Switzerland. In 2019, Thomas Baumert founded Alentis Therapeutics,[23] a clinical-stage, venture-backed biotech based in Switzerland,[24] developing monoclonal antibodies discovered with his team in his laboratory to treat fibrosis and cancer.[25]

References

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  1. ^ Baumert, Thomas; Huber, Michael; Mayer, Doris; Keppler, Dietrich (June 1989). "Ethanol-induced inhibition of leukotriene degradation by ω-oxidation". European Journal of Biochemistry. 182 (2): 223–229. doi:10.1111/j.1432-1033.1989.tb14821.x. ISSN 0014-2956. PMID 2544422.
  2. ^ Baumert, T. F.; Rogers, S. A.; Hasegawa, K.; Liang, T. J. (1996-11-15). "Two core promotor mutations identified in a hepatitis B virus strain associated with fulminant hepatitis result in enhanced viral replication". The Journal of Clinical Investigation. 98 (10): 2268–2276. doi:10.1172/JCI119037. ISSN 0021-9738. PMC 507676. PMID 8941643.
  3. ^ Baumert, Thomas F.; Ito, Susumu; Wong, David T.; Liang, T. Jake (May 1998). "Hepatitis C Virus Structural Proteins Assemble into Viruslike Particles in Insect Cells". Journal of Virology. 72 (5): 3827–3836. doi:10.1128/JVI.72.5.3827-3836.1998. ISSN 0022-538X. PMC 109606. PMID 9557666.
  4. ^ Lupberger, Joachim; Zeisel, Mirjam B.; Xiao, Fei; Thumann, Christine; Fofana, Isabel; Zona, Laetitia; Davis, Christopher; Mee, Christopher J.; Turek, Marine; Gorke, Sebastian; Royer, Cathy; Fischer, Benoit; Zahid, Muhammad N.; Lavillette, Dimitri; Fresquet, Judith (May 2011). "EGFR and EphA2 are host factors for hepatitis C virus entry and possible targets for antiviral therapy". Nature Medicine. 17 (5): 589–595. doi:10.1038/nm.2341. ISSN 1546-170X. PMC 3938446. PMID 21516087.
  5. ^ Zona, Laetitia; Lupberger, Joachim; Sidahmed-Adrar, Nazha; Thumann, Christine; Harris, Helen J.; Barnes, Amy; Florentin, Jonathan; Tawar, Rajiv G.; Xiao, Fei; Turek, Marine; Durand, Sarah C.; Duong, François H.T.; Heim, Markus H.; Cosset, François-Loïc; Hirsch, Ivan (March 2013). "HRas Signal Transduction Promotes Hepatitis C Virus Cell Entry by Triggering Assembly of the Host Tetraspanin Receptor Complex". Cell Host & Microbe. 13 (3): 302–313. doi:10.1016/j.chom.2013.02.006. ISSN 1931-3128. PMID 23498955.
  6. ^ Majzoub, Karim; Hafirassou, Mohamed Lamine; Meignin, Carine; Goto, Akira; Marzi, Stefano; Fedorova, Antonina; Verdier, Yann; Vinh, Joëlle; Hoffmann, Jules A.; Martin, Franck; Baumert, Thomas F.; Schuster, Catherine; Imler, Jean-Luc (November 2014). "RACK1 Controls IRES-Mediated Translation of Viruses". Cell. 159 (5): 1086–1095. doi:10.1016/j.cell.2014.10.041. ISSN 0092-8674. PMC 4243054. PMID 25416947.
  7. ^ a b Mailly, Laurent; Xiao, Fei; Lupberger, Joachim; Wilson, Garrick K.; Aubert, Philippe; Duong, François H. T.; Calabrese, Diego; Leboeuf, Céline; Fofana, Isabel; Thumann, Christine; Bandiera, Simonetta; Lütgehetmann, Marc; Volz, Tassilo; Davis, Christopher; Harris, Helen J. (May 2015). "Clearance of persistent hepatitis C virus infection in humanized mice using a claudin-1-targeting monoclonal antibody". Nature Biotechnology. 33 (5): 549–554. doi:10.1038/nbt.3179. ISSN 1546-1696. PMC 4430301. PMID 25798937.
  8. ^ Verrier, Eloi R.; Yim, Seung-Ae; Heydmann, Laura; El Saghire, Houssein; Bach, Charlotte; Turon-Lagot, Vincent; Mailly, Laurent; Durand, Sarah C.; Lucifora, Julie; Durantel, David; Pessaux, Patrick; Manel, Nicolas; Hirsch, Ivan; Zeisel, Mirjam B.; Pochet, Nathalie (November 2018). "Hepatitis B Virus Evasion From Cyclic Guanosine Monophosphate–Adenosine Monophosphate Synthase Sensing in Human Hepatocytes". Hepatology. 68 (5): 1695–1709. doi:10.1002/hep.30054. ISSN 0270-9139. PMC 6195855. PMID 29679386.
  9. ^ Verrier, Eloi R.; Weiss, Amélie; Bach, Charlotte; Heydmann, Laura; Turon-Lagot, Vincent; Kopp, Arnaud; Saghire, Houssein El; Crouchet, Emilie; Pessaux, Patrick; Garcia, Thomas; Pale, Patrick; Zeisel, Mirjam B.; Sureau, Camille; Schuster, Catherine; Brino, Laurent (2020-01-01). "Combined small molecule and loss-of-function screen uncovers estrogen receptor alpha and CAD as host factors for HDV infection and antiviral targets". Gut. 69 (1): 158–167. doi:10.1136/gutjnl-2018-317065. ISSN 0017-5749. PMC 6943243. PMID 30833451.
  10. ^ Pestka, Jan M.; Zeisel, Mirjam B.; Bläser, Edith; Schürmann, Peter; Bartosch, Birke; Cosset, Francois-Loïc; Patel, Arvind H.; Meisel, Helga; Baumert, Jens; Viazov, Sergei; Rispeter, Kay; Blum, Hubert E.; Roggendorf, Michael; Baumert, Thomas F. (2007-04-03). "Rapid induction of virus-neutralizing antibodies and viral clearance in a single-source outbreak of hepatitis C". Proceedings of the National Academy of Sciences. 104 (14): 6025–6030. Bibcode:2007PNAS..104.6025P. doi:10.1073/pnas.0607026104. ISSN 0027-8424. PMC 1851610. PMID 17392433.
  11. ^ Baumert, Thomas F.; Schuster, Catherine; Cosset, François-Loïc; Dubuisson, Jean; Hofmann, Maike; Tautz, Norbert; Zeisel, Mirjam B.; Thimme, Robert (April 2016). "Addressing the next challenges: A summary of the 22nd international symposium on hepatitis C virus and related viruses". Journal of Hepatology. 64 (4): 968–973. doi:10.1016/j.jhep.2015.12.021. ISSN 0168-8278. PMC 7613471. PMID 26780288.
  12. ^ Hamdane, Nourdine; Jühling, Frank; Crouchet, Emilie; El Saghire, Houssein; Thumann, Christine; Oudot, Marine A.; Bandiera, Simonetta; Saviano, Antonio; Ponsolles, Clara; Roca Suarez, Armando Andres; Li, Shen; Fujiwara, Naoto; Ono, Atsushi; Davidson, Irwin; Bardeesy, Nabeel (June 2019). "HCV-Induced Epigenetic Changes Associated With Liver Cancer Risk Persist After Sustained Virologic Response". Gastroenterology. 156 (8): 2313–2329.e7. doi:10.1053/j.gastro.2019.02.038. ISSN 0016-5085. PMC 8756817. PMID 30836093.
  13. ^ Jühling, Frank; Hamdane, Nourdine; Crouchet, Emilie; Li, Shen; El Saghire, Houssein; Mukherji, Atish; Fujiwara, Naoto; Oudot, Marine A; Thumann, Christine; Saviano, Antonio; Roca Suarez, Armando Andres; Goto, Kaku; Masia, Ricard; Sojoodi, Mozhdeh; Arora, Gunisha (2020-03-26). "Targeting clinical epigenetic reprogramming for chemoprevention of metabolic and viral hepatocellular carcinoma". Gut. 70 (1): 157–169. doi:10.1136/gutjnl-2019-318918. ISSN 0017-5749. PMC 7116473. PMID 32217639.
  14. ^ Crouchet, Emilie; Bandiera, Simonetta; Fujiwara, Naoto; Li, Shen; El Saghire, Hussein; Fernández-Vaquero, Mirian; Riedl, Tobias; Sun, Xiaochen; Hirschfield, Hadassa; Jühling, Frank; Zhu, Shijia; Roehlen, Natascha; Ponsolles, Clara; Heydmann, Laura; Saviano, Antonio (2021-09-17). "A human liver cell-based system modeling a clinical prognostic liver signature for therapeutic discovery". Nature Communications. 12 (1): 5525. Bibcode:2021NatCo..12.5525C. doi:10.1038/s41467-021-25468-9. ISSN 2041-1723. PMC 8448834. PMID 34535664.
  15. ^ Aizarani, Nadim; Saviano, Antonio; Sagar; Mailly, Laurent; Durand, Sarah; Herman, Josip S.; Pessaux, Patrick; Baumert, Thomas F.; Grün, Dominic (August 2019). "A human liver cell atlas reveals heterogeneity and epithelial progenitors". Nature. 572 (7768): 199–204. doi:10.1038/s41586-019-1373-2. ISSN 1476-4687. PMC 6687507. PMID 31292543.
  16. ^ Fofana, Isabel; Krieger, Sophie E.; Grunert, Fritz; Glauben, Sandra; Xiao, Fei; Fafi–Kremer, Samira; Soulier, Eric; Royer, Cathy; Thumann, Christine; Mee, Christopher J.; McKeating, Jane A.; Dragic, Tatjana; Pessaux, Patrick; Stoll–Keller, Francoise; Schuster, Catherine (September 2010). "Monoclonal Anti-Claudin 1 Antibodies Prevent Hepatitis C Virus Infection of Primary Human Hepatocytes". Gastroenterology. 139 (3): 953–964.e4. doi:10.1053/j.gastro.2010.05.073. ISSN 0016-5085. PMID 20685314.
  17. ^ Roehlen, Natascha; Saviano, Antonio; El Saghire, Houssein; Crouchet, Emilie; Nehme, Zeina; Del Zompo, Fabio; Jühling, Frank; Oudot, Marine A.; Durand, Sarah C.; Duong, François H. T.; Cherradi, Sara; Gonzalez Motos, Victor; Almeida, Nuno; Ponsolles, Clara; Heydmann, Laura (2022-12-21). "A monoclonal antibody targeting nonjunctional claudin-1 inhibits fibrosis in patient-derived models by modulating cell plasticity". Science Translational Medicine. 14 (676): eabj4221. doi:10.1126/scitranslmed.abj4221. ISSN 1946-6234. PMID 36542691.
  18. ^ Roehlen, Natascha; Muller, Marion; Nehme, Zeina; Crouchet, Emilie; Jühling, Frank; Del Zompo, Fabio; Cherradi, Sara; Duong, Francois H.T.; Almeida, Nuno; Saviano, Antonio; Fernández-Vaquero, Mirian; Riedl, Tobias; El Saghire, Houssein; Durand, Sarah C.; Ponsolles, Clara (February 2023). "Treatment of HCC with claudin-1-specific antibodies suppresses carcinogenic signaling and reprograms the tumor microenvironment". Journal of Hepatology. 78 (2): 343–355. doi:10.1016/j.jhep.2022.10.011. ISSN 0168-8278. PMID 36309131.
  19. ^ "Thomas Baumert: Researching Innovative Solutions for Fibrosis and Liver Cancer · Inserm". Inserm. Retrieved 2024-05-03.
  20. ^ "Lauréats ERC 2014 - Université de Strasbourg - Recherche". recherche.unistra.fr. Retrieved 2024-05-03.
  21. ^ "ERC Proof of concept 2022 "Innovation thérapeutique pour le cholangiocarcinome" - Université de Strasbourg". www.unistra.fr. Retrieved 2024-05-03.
  22. ^ "The DELIVER program for liver disease therapeutic innovation, laureate of the 5th call for university-hospital research projects in health (RHU)". imcbioplus.unistra.fr. 2021-12-16. Retrieved 2024-05-03.
  23. ^ mt@blueprint.dk (2019-04-30). "ALENTIS Therapeutics launches". Alentis Therapeutics. Retrieved 2024-05-03.
  24. ^ "Success story Alentis". BaseLaunch. Retrieved 2024-05-03.
  25. ^ "Claudin-1-targeted therapies break barriers in precision oncology". {{cite journal}}: Cite journal requires |journal= (help)
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