My laboratory at Tulane investigates how the hepatic adaptive plasticity relates to hepatitis C virus (HCV) microbial stress promotes hepatocellular carcinoma (HCC), primary liver cancer. My VA lab work on developing biomarker to detect liver cancer at an early stage.
Integrated stress response (ISR) is an evolutionarily conserved intracellular signaling pathway that programs cell to adapt to the multifaceted stress during chronic HCV infection. The ISR is a homeostatic mechanism that decreases global protein synthesis, while mRNAs translation of genes with upstream open reading frames (uORF) are increased to recover from stress. The ISR-mediated translational programming alters hepatic plasticity and fate-switching towards pluripotent stem cell-like phenotypes and their self-renewal. A robust HCC model has been developed in the liver humanized mouse after natural HCV infection to study how the ISR promotes hepatic plasticity and HCC. We have learned that the self-renewal of hepatic stem cells through symmetrical cell division leads to HCC in the humanized mouse. This mechanism is consistent with HCC developed in the human cirrhotic liver.
Complete List of Published Work in My Bibliography: URL: https://www.ncbi.nlm.nih.gov/myncbi/1ZaetAqlwlDQU/bibliography/public/
Selected Publications:
· 1.SrikantaDash, Yucel Aydin, Kyle E Widmer and Leela Nayak. Hepatocellular carcinoma mechanismsassociated with chronic HCV Infection and the impact of direct acting antiviraltreatment. Journal of Hepatocellular Carcinoma, 2020;7:1-32.
· 2.NúñezKG, Aydin Y, Sandow T, Thevenot P, Dash S, Cohen AJ. Expansion of immunosuppressivecell populations associates with tumor-derived exosome shedding in early-stageHCC patients undergoing locoregional therapy. American Journal of Transplantation,2020; 20: 60.
· 3.Dong Lin, Venu Reddy,Hanadi Osman, Adriana Lopez, Sadeq Radhi, Srikanta Dash and Yucel Aydin.Additional inhibition of Wnt/b-catenin signaling by Metformin in DAA treatmentsas a novel therapeutic strategy for HCV-infected patients. Cells, 2021;10;790.
· 4.YucelAydin, Ali R Koksal, Venu Reddy, Dong Lin, Hanadi Osman, Zahra Heidari, Sadeq RRhadhi, William C Wimley, Mansour Parsi, and Srikanta Dash. Extracellularvesicle release promotes viral replication during persistent HCV infection.Cells, 2021; 10 (5):984.
· 5.YucelAydin, Ali R, Lin Dong, John W. Scott,Paul Thevenot, Arie Cohen and Srikanta Dash. Experimentalvalidation of novel glypican 3 exosomes for the detection of hepatocellularcarcinoma in liver cirrhosis. J Hepatocellular Carcinoma, 2021;8:1579-1596.
· 6.Ali Riza Koksal,Nunez Kelly, PaulThevenot, Kyle Widmer, Leela Nayak, Martin Moehlen, Ari Cohen andSrikanta Dash. Impaired autophagy response in hepatocellular carcinoma enrichesglypican-3 in exosomes, not in the microvesicles. Journal of HepatocellularCarcinoma, 2022; Sept7; 9:959-972.
· 7.Dong Lin, Yijia Chen, Ali Riza Koksal, Srikanta Dash, YucelAydin. Targeting ER stress/PKA/GSK-3β/β-catenin pathway as a potential novelstrategy for hepatitis C virus -infected patients. Cell Communication andSignaling, 2023;21:102.
Key words: Virus and Cancer
