Translational hepatometabolic approaches

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Translational hepatometabolic approaches

Translational hepatometabolic approaches

Given the rise in metabolic diseases a sustained increase in the prevalence of chronic liver diseases such as metabolic dysfunction-associated steatotic liver disease (MASLD) is expected. The progression of chronic liver diseases leads to increased liver-specific and life-threatening complications, such as impaired liver regeneration, fibrosis, cirrhosis and hepatocellular carcinoma (HCC), which represent an enormous burden for the future. In the dynamic landscape of metabolic and cancer research, understanding the complex mechanisms of liver regeneration, fibrosis and hepatocarcinogenesis is crucial. Numerous alterations trigger pathological cellular signaling initiating steatosis, inflammation, fibrogenesis and malignant transformations. While targeted therapies and immunotherapies have advanced, enhancing their efficacy remains a critical concern. Our research focuses on liver regeneration, MASLD, fibrosis and HCC, aiming to identify new vulnerabilities within these diseases and integrate them into treatment strategies. Using state of the art techniques such as genetic screenings, different in-vitro and in vivo models, combining experimental and clinical data, we pioneer innovative approaches for managing liver diseases. Additionally, our laboratory investigates the immune signatures of chronic inflammatory conditions, shedding light on the interaction between lifestyle factors and pathogens in chronic liver diseases.

By elucidating the molecular and cellular pathways, we aim to address the urgent global health challenge presented by the rising prevalence of chronic liver dieseases.

PD Dr. med. Dr. rer. nat. Daniel Hartmann, M.Sc.

Head of the research group

Publications: Publikationen

Personenprofil: Mehr zur Person

Dr. Daniel Hartmann, MD, PhD, is a clinician-scientist at the M3 Research Institute, where he leads a research group investigating the molecular mechanisms behind liver regeneration, fibrosis, and hepatocarcinogenesis. In addition to his research role, Dr. Hartmann serves as a senior physician and is board-certified in visceral surgery at Department of General, Visceral and Transplantation Surgery, University Hospital of Tübingen. He obtained his medical degree from the University of Heidelberg, with subinternships at Duke University Medical Center and Massachusetts General Hospital. Following this, Dr. Hartmann pursued a PhD in molecular medicine at the University of Ulm, conducting research in the laboratories of Prof. K.L. Rudolph. After completing his residency at Klinikum rechts der Isar in Munich, he undertook a one-year fellowship at the Brothers of Mercy Hospital in Munich. Dr. Hartmann's extensive research contributions have been published in over 80 publications, including prestigious journals such as Cell, Cancer Cell, The Journal of Clinical Investigation, Gastroenterology, Hepatology, and Nature Communications. He has been honored with several awards, including the Walter Brendel Prize and the Ferdinand Sauerbruch Research Prize. Actively engaged in professional societies, Dr. Hartmann has been a member of the European Digestive Surgery Council since 2014 and represents the European Society for Surgery of the Alimentary Tract at the United European Gastroenterology Public Affairs Committee.

Dr.med. Baocai Wang

Postdoc

Personenprofil: Mehr zur Person

Herr Dr. med. Benedikt Kaufmann

Personenprofil: Mehr zur Person

Selected publications

Liver

metabolism and its implications

Regeneration

mechanisms

Cellular

signaling dynamics in HCC progression

Selected publications

1. Yin Y*, Sichler A*, Ecker J, Laschinger M, Liebisch G, Höring M, Basic M, Bleich A, Zhang XJ, Kübelsbeck L, Plagge J, Scherer E, Wohlleber D, Wang J, Wang Y, Steffani M, Stupakov P, Gärtner Y, Lohöfer F, Mogler C, Friess H, Hartmann D, Holzmann B*, Hüser N*, Janssen KP*. Gut microbiota promote liver regeneration through hepatic membrane phospholipid biosynthesis. Journal of Hepatology 2023 Apr;78(4):820-835. doi:10.1016/j.jhep.2022.12.028.Epub 2023 Jan 18. PMID: 36681162. (IF 30.083)
2. Kaufmann B, Leszczynska A, Reca A, Boosheri LM, Onyuru J, Tan ZH, Wree A, Friess H, Hartmann D, Papouchado B, Broderick L, Hoffman HM, Croker B, Zhu YP, Feldstein AE. NLRP3 activation in neutrophils induces lethal autoinflammation, liver inflammation, and fibrosis. EMBO Reports 2022. Nov 7;23(11):e54446. doi: 10.15252/embr.202154446. PMID: 36194627. (IF 9.421)
3. Wang J*, Wang Y*, Steffani M, Stöß C, Ankerst D, Friess H, Hüser N, Hartmann D. (*equal contribution) Novel risk classification based on pyroptosis-related genes defines immune microenvironment and pharmaceutical landscape for hepatocellular carcinoma. Cancers (Basel) 2022; 14(2):447. doi: 10.3390/cancers14020447. PMID: 35053610. (IF 6.639)
4. Schneider CV, Schneider KM, Teumer A, Rudolph KL, Hartmann D, Rader DJ, Strnad P. Association of telomere length with risk of disease and mortality. JAMA Internal Medicine 2022; 182(3):291-300, doi: 10.1001/jamainternmed.2021.7804. PMID: 35040871. (IF 21.873)
5. Dudek M, Pfister D, Donakonda S, Filpe P, Schneider A, Laschinger M, Hartmann D, Hüser N, Meiser P, Bayerl F, Inverso D, Wigger J, Sebode M, Öllinger R, Rad R, Reider S, Hegenbarth S, Anton M, Guillot A, Bowman A, Heide D, Müller F, Ramadori P, Leone V, Garcia-Caceres C, Gruber T, Seifert G, Kabat AM, Mallm JP, Reider S, Effenberg M, Roth S, Billeter AT, Müller-Stich B, Pearce EJ, Nolte-Koch F, Käser R, Tilg H, Thimme R, Boettler T, Tacke F, Dufour JF, Haller D, Murray PJ, Heeren R, Zehn D, Böttcher JP, Heikenwälder M, Knolle PA. Auto-aggressive CXCR6+ CD8 T cells cause liver immune pathology in NASH. Nature 2021; 592(7854):444-449. doi: 10.1038/s41586-021-03233-8. PMID: 33762736. (IF 42.778)
6. Zhang X*, Olsavszky V*, Yin Y, Wang B, Engleitner T, Öllinger R, Schledzewski K, Koch PS, Rad R, Schmid RM, Friess H, Goerdt S, Hüser N, Géraud C*, von Figura G*, Hartmann D*. (*equal contribution) Angiocrine hepatocyte growth factor signaling controls physiologic organ and body size and dynamic hepatocyte proliferation to prevent liver damage during regeneration. American Journal of Pathology 2020; 190(2):358-371. doi:10.1016/j.ajpath.2019.10.009. PMID: 31783007 (IF 4.069)
7. Baumann T, Dunkel A, Schmid C, Schmitt S, Hiltensperger M, Lohr K, Laketa V, Donakonda S, Ahting U, Lorenz-Depiereux B, Heil JE, Schredelseker J, Simeoni L, Fecher C, Körber N, Bauer T, Hüser N, Hartmann D, Laschinger M, Eyerich K, Eyerich S, Anton M, Streeter M, Wang T, Schraven B, Spiegel D, Assaad F, Misgeld T, Zischka H, Murray PJ, Heine A, Heikenwälder M, Korn T, Dawid C, Hofmann T, Knolle PA, Höchst B. Regulatory myeloid cells paralyze T cells through cell-cell transfer of the metabolite methylglyoxal. Nature Immunology 2020; 21(5):555-566. doi:10.1038/s41590-020-0666-9. PMID: 32327756. (IF 23.5)
8. Wang B, Kaufmann B, Engleitner T, Lu M, Mogler C, Olsavszky V, Öllinger R, Zhong S, Géraud C, Cheng Z, Rad RR, Schmid RM, Friess H, Hüser N, Hartmann D*, von Figura G* (*equal contribution). Brg1 promotes liver regeneration after partial hepatectomy via regulation of cell cycle. Scientific Reports 2019; 9(1):2320. doi:10.1038/s41598-019-38568-w. PMID: 30787318. (IF 4.122)
9. Cheng Z*, Liu L*, Zhang XJ*, Lu M, Wang Y, Assfalg V, Laschinger M, von Figura G, Sunami Y, Michalski CM, Kleeff J, Friess H, Hartmann D*, Hüser N* (*equal contribution). Peroxisome Proliferator-Activated Receptor gamma negatively regulates liver regeneration after partial hepatectomy via the HGF/c-Met/ERK1/2 pathways. Scientific Reports 2018; 8(1):11894. doi:10.1038/s41598-018-30426-5. PMID: 30089804. (IF 4.122)
10. Yuan D, Huang S, Berger E, Liu L, Gross N, Heinzman F, Ringelhan M, O’Connor T, Stadler M, Meister M, Weber J, Öllinger R, Simonavicius N, Reisinger F, Hartmann D, Meyer R, Reich M, Seehawer M, Leone V, Höchst B, Wohlleber D, Jörs S, Prinz M, Spalding D, Protzer U, Luedde T, Terracciano L, Matter M, Longerich T, Knolle P, Ried T, Keitel V, Geisler F, Unger K, Cinnamon E, Pikarsky E, Hüser N, Davis RJ, Tschaharganeh DF, Rad R, Weber A, Zender L, Haller D*, Heikenwalder M* (*equal contribution). Kupffer-cell derived TNF triggers cholangiocellular tumorigenesis through JNK due to chronic mitochondrial dysfunction and ROS. Cancer Cell 2017; 31(6):771-789.e6. doi:10.1016/j.ccell.2017.05.006. PMID: 28609656. (IF 22.844)
11. Begus-Nahrmann Y*, Hartmann D*, Kraus JM, Eshraghi P, Scheffold A, Grieb M, Rasche V, Schirmacher P, Lee HW, Kestler HA, Lechel A, Rudolph KL. (*equal contribution). Transient telomere dysfunction induces chromosomal instability and promotes carcinogenesis. Journal of Clinical Investigation 2012; 122(6):2283-2288. doi:10.1172/JCI61745. PMID: 22622037. (IF 13.251)
12. Hartmann D*, Srivastava U*, Thaler M, Kleinhans KN, N’Kontchou G, Scheffold A, Bauer K, Kratzer RF, Kloos N, Katz SF, Song Z, Begus-Nahrmann Y, Kleger A, von Figura G, Strnad P, Lechel A, Günes C, Potthoff A, Deterding K, Wedemeyer H, Ju Z, Song G, Xiao F, Gillen S, Schrezenmeier H, Mertens T, Ziol M, Friess H, Jarek M, Manns MP, Beaugrand M, Rudolph KL (*equal contribution). Telomerase gene mutations are associated with cirrhosis formation. Hepatology 2011; 53(5):1608-1617. doi:10.1002/hep.24217. PMID: 21520174. (IF 14.079)

The M3 Research Center
Malignome, Metabolome and Microbiome