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References
- 1 2 "Dr. George K. Michalopoulos MD".
- 1 2 "George Michalopoulos". scholar.google.com.
- 1 2 "ASIP Rous-Whipple Award". American Society for Investigative Pathology.
- 1 2 "Distinguished Scientific Achievement Award - American Liver Foundation". liverfoundation.org. July 6, 2023.
- 1 2 3 "George K. Michalopoulos, MD, PhD".
- ↑ Medicine, The McGowan Institute For Regenerative (21 May 2015). "Dr. George Michalopoulos Inducted Into AAP".
- 1 2 "Members of the First Section". Academy of Athens. November 23, 2015.
- ↑ "National Advisory Council Meeting - February 6-7, 2008 | National Institute on Alcohol Abuse and Alcoholism (NIAAA)". www.niaaa.nih.gov.
- ↑ "George K. Michalopoulos Junior Faculty Scholar Award Fund". American Society for Investigative Pathology.
- ↑ Zarnegar, R.; Michalopoulos, G. (15 June 1989). "Purification and biological characterization of human hepatopoietin A, a polypeptide growth factor for hepatocytes". Cancer Research. 49 (12): 3314–3320. PMID 2524251.[ non-primary source needed ]
- ↑ Naldini, L.; Vigna, E.; Narsimhan, R. P.; Gaudino, G.; Zarnegar, R.; Michalopoulos, G. K.; Comoglio, P. M. (April 1991). "Hepatocyte growth factor (HGF) stimulates the tyrosine kinase activity of the receptor encoded by the proto-oncogene c-MET". Oncogene. 6 (4): 501–504. PMID 1827664.[ non-primary source needed ]
- ↑ Lindroos, Pamela M.; Zarnegar, Reza; Michalopoulos, George K. (April 26, 1991). "Hepatocyte growth factor (hepatopoietin A) rapidly increases in plasma before DNA synthesis and liver regeneration stimulated by partial hepatectomy and carbon tetrachloride administration". Hepatology. 13 (4): 743–750. doi: 10.1002/hep.1840130422 . PMID 1826282.[ non-primary source needed ]
- ↑ Liu, Youhua; Bell, Aaron W.; Michalopoulos, George K.; Zarnegar, Reza (July 1994). "The mouse hepatocyte growth factor-encoding gene: structural organization and evolutionary conservation". Gene. 144 (2): 179–187. doi:10.1016/0378-1119(94)90376-X. PMID 8039703.[ non-primary source needed ]
- ↑ Stolz, D. B.; Mars, W. M.; Petersen, B. E.; Kim, T. H.; Michalopoulos, G. K. (15 August 1999). "Growth factor signal transduction immediately after two-thirds partial hepatectomy in the rat". Cancer Research. 59 (16): 3954–3960. PMID 10463591.[ non-primary source needed ]
- ↑ Cruise, Jennifer L.; Houck, Keith A.; Michalopoulos, George K. (15 February 1985). "Induction of DNA Synthesis in Cultured Rat Hepatocytes Through Stimulation of α 1 Adrenoreceptor by Norepinephrine". Science. 227 (4688): 749–751. doi:10.1126/science.2982212. PMID 2982212.[ non-primary source needed ]
- ↑ Kim, T; Mars, W M; Stolz, D B; Petersen, B E; Michalopoulos, G K (October 26, 1997). "Extracellular matrix remodeling at the early stages of liver regeneration in the rat". Hepatology. 26 (4): 896–904. doi: 10.1002/hep.510260415 . PMID 9328311.[ non-primary source needed ]
- ↑ Mars, W (June 1995). "Immediate early detection of urokinase receptor after partial hepatectomy and its implications for initiation of liver regeneration*1". Hepatology. 21 (6): 1695–1701. doi:10.1016/0270-9139(95)90477-8. PMID 7768515.
- ↑ Paranjpe, Shirish; Bowen, William C.; Mars, Wendy M.; Orr, Anne; Haynes, Meagan M.; DeFrances, Marie C.; Liu, Silvia; Tseng, George C.; Tsagianni, Anastasia; Michalopoulos, George K. (21 October 2016). "Combined systemic elimination of MET and epidermal growth factor receptor signaling completely abolishes liver regeneration and leads to liver decompensation". Hepatology. 64 (5): 1711–1724. doi:10.1002/hep.28721. PMC 5074871 . PMID 27397846.
- ↑ Apte, Udayan; Gkretsi, Vasiliki; Bowen, William C.; Mars, Wendy M.; Luo, Jian-Hua; Donthamsetty, Shashikiran; Orr, Ann; Monga, Satdarshan P.S.; Wu, Chuanyue; Michalopoulos, George K. (September 26, 2009). "Enhanced liver regeneration following changes induced by hepatocyte-specific genetic ablation of integrin-linked kinase". Hepatology. 50 (3): 844–851. doi:10.1002/hep.23059. PMC 2914599 . PMID 19575460.[ non-primary source needed ]
- ↑ Liu, Bowen; Bell, Aaron W.; Paranjpe, Shirish; Bowen, William C.; Khillan, Jaspal S.; Luo, Jian-Hua; Mars, Wendy M.; Michalopoulos, George K. (September 26, 2010). "Suppression of liver regeneration and hepatocyte proliferation in hepatocyte-targeted glypican 3 transgenic mice". Hepatology. 52 (3): 1060–1067. doi:10.1002/hep.23794. PMC 2936713 . PMID 20812357.[ non-primary source needed ]
- ↑ Gkretsi, Vasiliki; Apte, Udayan; Mars, Wendy M.; Bowen, William C.; Luo, Jian-Hua; Yang, Yu; Yu, Yan P.; Orr, Ann; St.-Arnaud, René; Dedhar, Shoukat; Kaestner, Klaus H.; Wu, Chuanyue; Michalopoulos, George K. (December 26, 2008). "Liver-specific ablation of integrin-linked kinase in mice results in abnormal histology, enhanced cell proliferation, and hepatomegaly". Hepatology. 48 (6): 1932–1941. doi:10.1002/hep.22537. PMC 2597430 . PMID 18846549.[ non-primary source needed ]
- ↑ Bhave, Vishakha S.; Mars, Wendy; Donthamsetty, Shashikiran; Zhang, Xiyue; Tan, Langzhu; Luo, Jianhua; Bowen, William C.; Michalopoulos, George K. (July 2013). "Regulation of Liver Growth by Glypican 3, CD81, Hedgehog, and Hhex". The American Journal of Pathology. 183 (1): 153–159. doi:10.1016/j.ajpath.2013.03.013. PMC 3702736 . PMID 23665349.[ non-primary source needed ]
- 1 2 Xue, Yuhua; Mars, Wendy M.; Bowen, William; Singhi, Aatur D.; Stoops, John; Michalopoulos, George K. (June 2018). "Hepatitis C Virus Mimics Effects of Glypican-3 on CD81 and Promotes Development of Hepatocellular Carcinomas via Activation of Hippo Pathway in Hepatocytes". The American Journal of Pathology. 188 (6): 1469–1477. doi:10.1016/j.ajpath.2018.02.013. PMC 5975625 . PMID 29577937.[ non-primary source needed ]
- ↑ Qi, Jingshu; Dai, Yunkai; Sun, Xin; Liu, Chenghai (October 26, 2023). "Mechanism of liver regeneration: 20-year bibliometric analyses". Frontiers in Pharmacology. 14. doi: 10.3389/fphar.2023.1190559 . PMC 10293616 . PMID 37383706.
- ↑ Michalopoulos, George K.; Barua, Lindsay; Bowen, William C. (March 26, 2005). "Transdifferentiation of rat hepatocytes into biliary cells after bile duct ligation and toxic biliary injury". Hepatology. 41 (3): 535–544. doi:10.1002/hep.20600. PMC 1821079 . PMID 15726663.[ non-primary source needed ]
- ↑ Limaye, Pallavi B; Alarcón, Gabriela; Walls, Andrew L; Nalesnik, Michael A; Michalopoulos, George K; Demetris, Anthony J; Ochoa, Erin R (August 2008). "Expression of specific hepatocyte and cholangiocyte transcription factors in human liver disease and embryonic development". Laboratory Investigation. 88 (8): 865–872. doi:10.1038/labinvest.2008.56. PMC 2631390 . PMID 18574450.[ non-primary source needed ]
- ↑ Limaye, Pallavi B.; Bowen, William C.; Orr, Anne V.; Luo, Jianhua; Tseng, George C.; Michalopoulos, George K. (May 26, 2008). "Mechanisms of hepatocyte growth factor-mediated and epidermal growth factor-mediated signaling in transdifferentiation of rat hepatocytes to biliary epithelium". Hepatology. 47 (5): 1702–1713. doi:10.1002/hep.22221. PMC 2615562 . PMID 18398918.[ non-primary source needed ]
- ↑ Michalopoulos, George K. (July 26, 2018). "The Regenerative Altruism of Hepatocytes and Cholangiocytes". Cell Stem Cell. 23 (1): 11–12. doi: 10.1016/j.stem.2018.06.006 . PMID 29979985.[ non-primary source needed ]
- ↑ Nalesnik, Michael A.; Tseng, George; Ding, Ying; Xiang, Guo-Sheng; Zheng, Zhong-liang; Yu, YanPing; Marsh, James W.; Michalopoulos, George K.; Luo, Jian-Hua (April 2012). "Gene Deletions and Amplifications in Human Hepatocellular Carcinomas". The American Journal of Pathology. 180 (4): 1495–1508. doi:10.1016/j.ajpath.2011.12.021. PMC 3657620 . PMID 22326833.[ non-primary source needed ]
- ↑ Koral, Kelly; Haynes, Meagan; Bowen, William C.; Orr, Anne; Mars, Wendy; Michalopoulos, George K. (September 2018). "Lymphocyte-Specific Protein-1 Controls Sorafenib Sensitivity and Hepatocellular Proliferation through Extracellular Signal-Regulated Kinase 1/2 Activation". The American Journal of Pathology. 188 (9): 2074–2086. doi:10.1016/j.ajpath.2018.06.005. PMC 6854472 . PMID 30126548.[ non-primary source needed ]
- ↑ Koral, Kelly; Paranjpe, Shirish; Mars, Wendy; Michalopoulos, George (April 2014). "Leukocyte specific protein-1: a novel regulator of hepatoma proliferation and migration (144.10)". The FASEB Journal. 28 (S1). doi: 10.1096/fasebj.28.1_supplement.144.10 .[ non-primary source needed ]
- ↑ Bhushan, Bharat; Banerjee, Swati; Paranjpe, Shirish; Koral, Kelly; Mars, Wendy M.; Stoops, John W.; Orr, Anne; Bowen, William C.; Locker, Joseph; Michalopoulos, George K. (November 2019). "Pharmacologic Inhibition of Epidermal Growth Factor Receptor Suppresses Nonalcoholic Fatty Liver Disease in a Murine Fast-Food Diet Model". Hepatology. 70 (5): 1546–1563. doi:10.1002/hep.30696. PMID 31063640. S2CID 147706721.[ non-primary source needed ]