Hsu-Wen Chao
JobTitle： Associate Professor
CurrentJob： Associate Professor of CGU
E-mail： chaohw3619@cgu.edu.tw
Phone： 3480, 3487
Education： Ph.D. in NDMC, Taiwan
Expertise： Chronohepatology, Genome Content Transition, Circadian Rhythm...
Research & Academic Experience
2026.08 – present Associate Professor. Chang Gung University.
2026.01 – lifetime EMBO outstanding early-career group leaders.
2022.01 – 2025.12 EMBO Global Investigator.
2021.02 – 2026.07 Associate Professor. Department of Physiology, School of Medicine, Taipei Medical University.
2016.12 – 2021.01 Assistant Professor. Department of Physiology, School of Medicine, Taipei Medical University.
Lab
Genome Content Switch Lab.Research Interests and Laboratory Features
The research core of our laboratory is established at the intersection of Chronohepatology and Genome Content Transition. Our team is dedicated to deciphering a fundamental scientific puzzle: How does the liver, the body's most critical metabolic and circadian organ, modulate the molecular switches of polyploidization and polyploidy reversal to dynamically adapt under physiological and pathological states when confronted with circadian clock disruption and environmental stress shocks? Based on our team's published series of studies, our research can be systematically deconstructed into the following four major tracks to decode the triangular network of circadian rhythms, genome transition, and preneoplastic lesions：
1. Molecular Regulatory Mechanisms of the Circadian Clock on Hepatic Polyploidy
Under normal physiological conditions, the mammalian liver exhibits a unique and prevalent phenomenon known as polyploidy (the presence of more than two sets of homologous chromosomes within a single cell nucleus). In our first paper (Nature Communications, 2017), our team linked the biological clock with this specific cellular trait for the first time, discovering that the circadian clock serves as a master timer controlling the developmental progression of hepatocyte polyploidization. Our research demonstrated that mutations in the core clock gene Periods, or circadian disturbances induced by environmental stress, directly disrupt the 24-hour dynamic oscillation of the downstream Mkp1-Erk1/2 signaling pathway. This rhythmic dysregulation leads to cytokinesis failure during hepatocyte mitosis, thereby abnormally accelerating the transformation of normal diploid or low-ploidy hepatocytes into hyperpolyploid cells.
2. Hepatocyte "Hyperpolyploidization" as an Initiator of Hepatic Preneoplastic Lesions
The academic community historically considered polyploidization a protective mechanism against liver aging or metabolic stress. However, in our second paper (Nature Communications, 2021), our team proposed a subversive translational medicine perspective: Excessive hepatocyte polyploidization (hyperpolyploidization) is essentially the onset of preneoplastic lesions. Utilizing animal models, we demonstrated that when hepatocytes are pushed toward hyperpolyploidy by chronic inflammation or circadian dysregulation, the excessive genomic content exposes the cells to extreme chromosomal instability (CIN) during chromosome segregation. Subsequently, when these cells undergo polyploidy reversal to revert to a lower ploidy state, the process triggers a genomic "reshuffling," which directly drives malignant transformation and culminates in the formation of hepatic preneoplastic lesions.
3. Whole-Nucleus Elimination Regulating the Polyploidy Reversal Defense Line to Suppress Tumorigenesis
Our laboratory discovered that when mice are exposed to genotoxic environmental stress, the nuclear number status of their hepatocytes alters. This change represents a peculiar phenomenon of whole-nucleus elimination achieved through the removal of specific nuclei. We found that whole-nucleus elimination can be viewed as a cellular self-rescue and defense mechanism when facing devastating DNA damage. It directly packages and eliminates highly mutated, potentially tumorigenic nuclear materials, preventing these cancer-driving genetic mutations from entering the subsequent mitosis, thereby maintaining the genome integrity of the entire liver tissue. Fundamentally, it serves as a massive form of selective nucleophagy (macro-nucleophagy), acting as a critical defensive player and the ultimate genomic janitor in tumor suppression and anticancer fields.
4. The Practice of "Chronopharmacology" and Targeted Precision Medicine
In collaboration with Professor Huatao Chen from Northwest A&F University, our laboratory co-developed "CircaVal," a big data and multi-omics circadian rhythm analysis platform. This platform executes precise calculations using a specialized rhythmicity algorithm (Rhythmicity Score Explorer) tailored for high-throughput sequencing data (such as RNA-seq, Nascent-seq/nascent transcriptome, and Ribo-seq/translatome). By interfacing with the Chang Gung Research Database (CGRD) and patient tissue specimens, we constructed Taiwan’s first "Post-Viral HBV Temporal Targeted Medicine Precision Prediction Platform," which enables the decoding of temporal targets showing 24-hour dynamic fluctuations amid vast clinical datasets.Furthermore, we develop chronotherapy strategies to evaluate the optimal "time window" within a day for administering targeted anticancer drugs and anti-inflammatory inhibitors. This approach aligns with the rhythmicity of hepatic clock genes to maximize the eradication of preneoplastic cells while utilizing time differentials to perfectly shield normal hepatocyte mitochondria from drug toxicities, seamlessly bridging clinical big data with fundamental molecular biology experiments.
References
1. C.-S. Wu¥, W.-H. Lu¥, M.-C. Hung*, Y.-S. Huang*, and H.-W. Chao¥*. From polyploidization to polyploidy reversal, the role in normal and disease states. Trends in Genetics. 2022 Oct 38(10):991-995. (¥ Equal contribution), (* Corresponding) (IF=12.9; Field order: 4/191)
2. H. Lin¥, Y.-S. Huang¥, J.-M. Fustin, M. Doi, H. Chen, H.-H. Lai, S.-H. Lin, Y.-L. Lee, P.-C. King, H.-S. Hou, H.-W. Chen, P.-Y. Young, and H.-W. Chao¥*, Hyperpolyploidization of hepatocyte initiates preneoplastic lesion formation in the liver. Nature Communications, 2021 Jan 28; 12(1):645. (¥ Equal contribution) (*, Corresponding) (IF=18.1; Field order: 4/191)
3. H.-W. Chao, M. Doi, J.-M. Fustin, H. Chen, Y. Maeda, H. Hayashi, R. Tanaka, M. Sugawa, N. Mizukuchi, Y. Yamaguchi, J. Yasunaga, M. Matsuoka, M. Sakai, M. Matsumoto, S. Hamada, H Okamura*, Circadian Clock Regulates Hepatic Polyploidy by Modulating Mkp1-ERk1/2 Signalling Pathway. Nature Communications, 2017 Dec 21; 8(1):2238. (IF=18.1; Field order: 4/191)
Publications
1. W.-B. Lu, Y.-S. Huang, J.-C. Wu, L.-W. Chen, I-W. Lin, P.-C. Chen, P.-H. Chen, C.-Y. Huang, T.-T. Tai, S.-H. Huang, S.-H. Wu, F.-S. Wang, H.-W. Chao *, M.-H. Tai *. Irisin Gene Delivery Elicits Sustained Amelioration of Diabetes in Akita Mice via Insulin-Independent Regulation of Hepatic Glucose Metabolism. 2026 Aug., Diabetes. Accepted (* Corresponding) (IF=9.3; Field order: 13/198)
# This study identifies an insulin-independent pathway of the liver to ameliorate diabetes symptoms through upregulation of Irisin in the hepatocytes in Akita-diabetic mice.
2. W. Yang, X. Wang, B. Xiao, C. Li, Y. Guo, K. Tang, A. Wang, H.-W. Chao*, Y. Jin*, H. Chen*. Berberine alleviates LPS-induced inflammatory response by targeted activation of NR1D1 in bovine endometrial epithelial cells. International Immunopharmacology, 2026 Aug. 15, (13) 116858. (* Corresponding) (IF=5.6; Field order: 48/356)
3. G. Han, X. Wu, X. Xiao, T. Guo, D. Li, H. Zhang, D. Gao, C. Li, A. Wang, H.-W. Chao*, Y. Jin*, H. Chen*. RhythmInsight: An Interactive Web Platform for Circadian and Diurnal Rhythmic Analysis and Visualization. Journal of Biological Rhythms, 2026 May 05, 07487304261437377. (* Corresponding) (IF=3.0; Field order: 26/106)
4. H.-W. Chao, Y.-M.-J. Lin, C.-S. Wu, Biomarker-Based Precision Prediction of Immunotherapy Response in Hepatocellular Carcinoma. Diagnostics, 2025 Dec. 28, 16 (1), 85 (IF=3.6; Field order: 61/336)
5. C.-S. Wu, T.-Y. Lee, H.-W. Chao*. Targeting glypican-3 as a new frontier in liver cancer therapy. World journal of hepatology, 2025 Sep. 27, 7 (9), 107671 (* Corresponding) (IF=3.4; Field order: 55/153)
6. G. Han, D. Li, H. Zhang, C. Li, L. Yang, T. Ma, X. Wang, B. Ma, X. Wu, Y. Tao, Z. Wang, A. Wang, H.-W. Chao*, Y. Jin* & H. Chen*. A transcriptomic Dataset of Liver tissues from Global and Liver Specific Bmal1 Knockout Mice. Scientific Data. 2025 Feb. 13;18 (6):4822-4839. (* Corresponding) (IF=7.2; Field order: 17/140)
# This study highlights the critical role of BMAL1 in the liver function by transcriptomic data from global and liver-specific Bmal1 knockout mice.
7. Y.-W. Chao¥, Y.-L. Lee¥, C.-S. Tseng¥, L. Wang, K.-C. Hsia, H. Chen, J.-M. Fustin, S. Azeem, T.-T. Chang, Y.-P. Hsueh*, Y.-S. Huang*, H.-W. Chao¥*. Improved CaP nanoparticles transforming nucleic acid and protein delivery to neural primary culture and stem cells. ACS NANO. 2024 Feb. 13;18 (6):4822-4839. (¥ Equal contribution) (* Corresponding) (IF=17.2; Field order: 24/439)
# The first report provides the highly cost-effective non-viral system for delivery of nucleic acid and protein into primary cells.
8. W. Yang; M. Jin; Y. Wang; H. Zhao; X. Wang; Y. Guo; C. Li; B. Xiao; H. Zhang; K. Fouzia; A. Wang; H.-W. Chao*, Y. Jin*, H. Chen*. NR1D1 activation alleviates inflammatory response through inhibition of IL-6 expression in bovine endometrial epithelial cells. International Journal of Biological Macromolecules. 2024 Nov. 283, 137642 (* Corresponding) (IF=8.7; Field order: 5/95)
# The first report provides the evidence that activating the circadian clock receptor NR1D1 alleviates bovine endometritis.
9. H. Zhao, G. Han, Z. Jiang, D. Gao, H. Zhang, L. Yang, T. Ma, L. Gao, A. Wang, Q. Li, H.-W. Chao＊, Y. Jin＊, H. Chen＊. Identification of BMAL1-Regulated circadian genes in mouse liver and their potential association with hepatocellular carcinoma: Gys2 and Upp2 as promising candidates. Biochemical and Biophysical Research Comms. 2024 Feb. (696), 149422. (* Corresponding) (IF=2.5; Field order: 45/81)
10. C.-S. Wu¥, W.-H. Lu¥, M.-C. Hung*, Y.-S. Huang*, and H.-W. Chao¥*. From polyploidization to polyploidy reversal, the role in normal and disease states. Trends in Genetics. 2022 Oct 38(10):991-995. (¥ Equal contribution), (* Corresponding) (IF=12.9; Field order: 4/191)
# The invited forum article to discuss the issue of genome content switch in organisms.
11. C.-W. Lin, D. Septyaningtrias¥, H.-W. Chao¥, M. Kond, K. Atarashi, K. Takeshita, K. Tamada, J. Nomura, Y. Sasagawa, K. Tanaka, I. Nikaido, K. Honda, T. J. McHugh and T. Takumi, A common epigenetic mechanism across different cellular origins underlies systemic immune dysregulation in autism. Molecular Psychiatry, 2022 May 02, (¥ Equal contribution) (IF=10.4; Field order: 11/313)
12. H.-W. Chao¥, W.-H. Lu¥, P.-Y. Lin, S.-H. Lin, T.-H. Liu, and Y.-S. Huang. CPEB3-downregulated Nr3c1 mRNA translation confers resilience to developing posttraumatic stress disorder-like behavior in fear-conditioned mice. Neuropsychopharmacology, 2021 May 03, 46, p1669–1679 (¥ Equal contribution) (IF=7.6; Field order: 24/354)
# The first critical report demonstrates the role of RNA-binding protein in the formation of post-traumatic stress disorder.
13. Y. Xiao, L. Zhao, W. Li, X. Wang, T. Ma, L. Yang, L. Gao, C. Li, M. Zhang, D. Yang, J. Zhang, H. Jiang, H. Zhao, Y. Wang, H.-W. Chao, A. Wang, Y. Jin, H. Chen, Circadian clock gene BMAL1 controls testosterone production by regulating steroidogenesis-related gene transcription in goat Leydig cells. Journal of Cellular Physiology, 2021 Feb 17, 236 (9), p6706-6725 (IF=4.0; Field order: 23/85)
Assistant Professor Period (2016/12~2021/01)
14. H. Lin¥, Y.-S. Huang¥, J.-M. Fustin, M. Doi, H. Chen, H.-H. Lai, S.-H. Lin, Y.-L. Lee, P.-C. King, H.-S. Hou, H.-W. Chen, P.-Y. Young, and H.-W. Chao¥*, Hyperpolyploidization of hepatocyte initiates preneoplastic lesion formation in the liver. Nature Communications, 2021 Jan 28; 12(1):645. (¥ Equal contribution) (*, Corresponding) (IF=18.1; Field order: 8/135)
# Featured in a Nature Communications Editors’ Highlights webpage “Cancer”.
# Commented by Nature Communications, entitled "Ploidy dynamics increase the risk of liver cancer initiation".
# Recommended by Faculty Opinions as Very Good article.
15. Y.-S. Huang, K.-C. Lu, H.-W. Chao, A. Chen, T.-K. Chao, C.-Y. Guo, H.-Y. Hsieh, H.-M. Shih, H.-K. Sytwu, C.-C. Wu, The MTNR1A mRNA is stabilized by the cytoplasmic hnRNPL in renal tubular cells. Journal of Cellular Physiology., 2020 July 30; 236 (3): p2023-2035 (IF=4.0; Field order: 23/85)
16. H.-W. Chao¥, Y.-T. Lai¥, A. C.-Y. Lai, S.-H. Lin, Y.-J. Chang, and Y.-S. Huang, CPEB2-activated PDGFRα mRNA translation is essential for myofibroblast proliferation and pulmonary alveologenesis., Journal of Biomedical Science, 2020 Apr 15; 27(1):52. (¥ Equal contribution) (IF=14.5; Field order: 8/191)
17. H.-W. Chao, M. Doi, J.-M. Fustin, H. Chen, Y. Maeda, H. Hayashi, R. Tanaka, M. Sugawa, N. Mizukuchi, Y. Yamaguchi, J. Yasunaga, M. Matsuoka, M. Sakai, M. Matsumoto, S. Hamada, H Okamura*, Circadian Clock Regulates Hepatic Polyploidy by Modulating Mkp1-ERk1/2 Signalling Pathway. Nature Communications, 2017 Dec 21; 8(1):2238. (IF=18.1; Field order: 8/135)
# The first critical report connects circadian clock to genome content switch and pathological polyploidy of the liver.
18. C.-S. Tseng, H.-W. Chao, H.-S. Huang and Y.-S. Huang, Olfactory Experience- and Developmental Stage-Dependent Control of CPEB4 Regulates c-Fos mRNA Translation for Granule Cell Survival. Cell Reports, 2017 Nov 21; 21(8):2264-2276. (IF=7.7; Field order: 36/205)