Arbeitsgruppe: RNA-Therapeutika und Leberregeneration
Das Hauptziel unseres Labors ist die Entwicklung molekularmedizinischer Therapieansätze für die Behandlung von Lebererkrankungen. Um dies zu erreichen, nutzen wir interdisziplinäre Ansätze, die RNA-Therapeutika, zellkulturbasierte Krankheitsmodellierung, Mausmodelle und Biomaterialien aus klinischen Proben umfassen. Im Laufe der Jahre hat unsere Forschungsgruppe die funktionelle Relevanz von Messenger-RNAs, kleinen RNAs und Wachstumsfaktoren während des Fortschreitens akuter und chronischer Lebererkrankungen aufgedeckt. Darüber hinaus haben wir entdeckt, dass die durch Transkriptionsfaktoren induzierte In-vivo-Reprogrammierung in Leberzellen ein immenses Potenzial für die Abschwächung von Leberfibrose und Leberzirrhose birgt. Derzeit untersuchen wir die Mechanismen, die der Umwandlung des Zellschicksals von Leberzellen während der Reprogrammierung zugrunde liegen. Mithilfe der molekularen Regulatoren, die wir im Laufe der Jahre identifiziert haben, wollen wir RNA-Therapeutika zur Linderung von Lebererkrankungen entwickeln.
Weitere Informationen
- DFG
- REBIRTH Research Center for Translational and Regenerative Medicine
- Funding from biopharmaceutical companies
Research Group RNA Therapeutics & Liver Regeneration
Publications (selected)
- Markovic J, Li R, Khanal R, Peng Q, Mobus S, Yuan Q, Engel B, Taubert R, Vondran FWR, Bantel H, Singh MK, Cantz T, Buning H, Wedemeyer H, Ott M, Balakrishnan A, Sharma AD. Identification and functional validation of miR-190b-5p and miR-296-3p as novel therapeutic attenuators of liver fibrosis. Journal of Hepatology 2024 Aug 31:S0168-8278(24)02492-9. doi:10.1016/j.jhep.2024.08.014.
- Li R, Balakrishnan A, Ott M, Sharma AD. Bioartificial liver with reprogrammed hepatocytes ready for prime time. (Invited preview) Cell Stem Cell 30, May 4, 2023.
- Heinenn N, Khanal R, Westhoven S, Klöhn M, Herrmann S, Herrmann M, Tuoc T, Ulmke PA, Nguyen HD, Nguyen HP, Steinmann E, Todt D, Brown RJP, Sharma AD, Pfaender S. Gut 2024 Sep 9;73(10):e14. doi: 10.1136/gutjnl-2023-330961.
- Yang T, Poenisch M, Khanal R, Hu Q, Dai Z, Li R, Song G, Yuan Q, Yao Q, Shen X, Taubert R, Engel B, Jaeckel E, Vogel A, Falk CS, Schambach A, Gerovska D, Araúzo-Bravo MJ, Vondran FWR, Cantz T, Horscroft N, Balakrishnan A, Chevessier F, Ott M and Sharma AD. Novel mRNA-based therapeutic approach of delivering transcription factor HNF4A attenuates liver fibrosis. Journal of Hepatology 2021; Dec;75(6):1420-1433.
- Yang D, Dai Z, Yang T, Balakrishnan A, Yuan Q, Vondran FWR, Manns MP, Ott M, Cantz T, Sharma AD. MicroRNA-125b-5p regulates hepatocyte proliferation during the termination phase of liver regeneration. Hepatology Communications 2020; Sep 15;4(12):1851-1863.
- Arnold F, Mahaddalkar PU, Kraus JM, Zhong X, Bergmann W, Srinivasan D, Gout J, Roger E, Beutel AK, Zizer E, Tharehalli U, Daiss N, Russell R, Perkhofer L, Oellinger R, Lin Q, Azoitei N, Weiss FU, Lerch MM, Liebau S, Katz SF, Lechel A, Rad R, Seufferlein T, Kestler HA, Ott M, Sharma AD, Hermann PC, Kleger A. Functional Genomic Screening During Somatic Cell Reprogramming Identifies DKK3 as a Roadblock of Organ Regeneration. Adv Sci (Weinh). 2021;8(14):2100626.
- Dai Z, Song G, Balakrishnan A, Yang T, Yuan Q, Möbus S, Weiss AC, Bentler M, Zhu J, Jiang XM, Shen X, Bantel H, Jaeckel E, Kispert A, Vogel A, Saborowski A, Büning H, Manns MP, Cantz T, Ott M and Sharma AD. Growth differentiation factor 11 attenuates liver fibrosis via expansion of liver progenitor cells. Gut 2020;69(6):1104-1115.
- Dai Z, Ott M, Sharma AD. Equal opportunity offer for all hepatocytes. (Editorial) Journal of Hepatology 2020 Jul;73(1):6-8.
- Krooss SA, Dai Z, Schmidt F, Rovai A, Fakhiri J, Dhingra A, Yuan Q, Yang T, Balakrishnan A, Steinbruck L, Srivaratharajan S, Manns MP, Schambach A, Grimm D, Bohne J, Sharma AD, Buning H, Ott M. Ex Vivo/In vivo Gene Editing in Hepatocytes Using "All-in-One" CRISPR-Adeno-Associated Virus Vectors with a Self-Linearizing Repair Template. iScience. 2020;23(1):100764.
- Song G, Yuan Q, Dai Z, Tsay HC, Shen X, Ott M, Sharma AD. Conversion of fibroblasts to hepatocyte-like cells in vivo. Methods Mol Biol. 2019;1905:103-115.
- Tsay HC, Yuan Q, Balakrishnan A, Kaiser M, Möbus S, Kozodrowska E Farid M, Tegtmeyer PK, Borst K, Vondran FWR, Kalinke U, Kispert A, Manns MP, Ott M, Sharma AD. Hepatocyte-specific suppression of microRNA-221-3p mitigates liver fibrosis. Journal of Hepatology 2019 Apr;70(4):722-734.
- Song G, Pacher M, Balakrishnan A, Yuan Q, Tsay H-C, Yang D, Reetz J, Brandes S, Dai Z, Pützer BM, Arauzo-Bravo MJ, Steinemann D, Luedde T, Schwabe RF, Manns MP, Schöler HR, Schambach A, Cantz T, Ott M, Sharma AD (2016). Direct reprogramming of hepatic myofibroblasts into hepatocytes in vivo attenuates liver fibrosis. Cell Stem Cell. 18(6):797-808.
- Yang D, Yuan Q, Balakrishnan A, Bantel H, Klusmann JH, Manns MP, Ott M, Cantz T, Sharma AD (2016). MicroRNA-125b-5p mimic inhibits acute liver failure. Nat Commun. 7:11916. doi: 10.1038/ncomms11916.
- Möbus S, Yang D, Yuan Q, Lüdtke TH, Balakrishnan A, Sgodda M, Rani B, Kispert A, Vogel A, Manns MP, Ott M, Cantz T, Sharma AD. MicroRNA-199a-5p inhibition enhances liver repopulation ability of human embryonic stem cell-derived hepatic cells. Journal of Hepatology 2015;62:101-10.
- Yuan Q, Loya K, Rani B, Möbus S, Balakrishnan A, Lamle J, Cathomen T, Vogel A, Manns MP, Ott M, Cantz T, Sharma AD. MicroRNA-221 overexpression accelerates hepatocyte proliferation during liver regeneration. Hepatology 2013;57(1):299-310.
Unsere Arbeitsgruppe
Medizinische Hochschule Hannover OE 6817
Carl-Neuberg-Str. 1
30625 Hannover
Telefon +49 511 532-5255
- Antonia Hapke (BTA)
- Jovana Markovic (PhD student)
- Alexandra Bogomolova (PhD student)
- Ruomeng Li (PhD student)
- Rajendra Khanal (PhD student)
- Xiaowei Zhong (PhD student)
- Selina Möbus (PhD student and later postdoc: currently working as scientist at Lophius Biosciences Gmbh, Regensburg, Germany)
- Dakai Yang (PhD student and later postdoc: currently working as a postdoc at Stanford, CA, USA)
- Guangqi Song (PhD student: currently working as a Group leader, at Shanghai Institute of Liver diseases, China)
- Zhen Dai (PhD student and later postdoc: currently working as a group leader in Guangzhou Institutes of Biomedicine and Health, Guangzhou, China)
- Taihua Yang (PhD student: currently working as group leader at the Department of Liver Surgery, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China)
- Helena Anke (MD student: currently at Hannover Medical School)
- Daniela Vallejo Guerra (Trainee: currently working as a postdoc at Center for Aging and Regeneration Santiago, Chile)
- Annabelle Hartwig (BTA)
