Chiou-Hwa Yuh, Ph.D.
Institute of Molecular and Genomic Medicine
Ph.D., Microbiology and Immunology, National Yang-Ming Medical College, Taipei, Taiwan (1992)
B.S., Biology, Fu-Jen Catholic University, Taipei, Taiwan (1987)
2015/10 – present
Investigator, Division of Molecular and Genomic Medicine, National Health Research Institutes, Zhunan, Taiwan
2015/10 – present
Joint Professor, Department of the Biological Science & Technology, National Chiao Tung University, HsincChu, Taiwan
2015/10 – present
Adjunct Professor, Institute of Bioinformatics and Structural Biology, National Tsing Hua University, HsincChu, Taiwan
2007/08 – 2015/09
Joint Associate Professor, Department of the Biological Science & Technology, National Chiao Tung University, HsincChu, Taiwan
2006/08 – 2015/09
Adjunct Associate Professor, Institute of Bioinformatics and Structural Biology, National Tsing Hua University, HsincChu, Taiwan
2005/01 – 2015/09
Associate Investigator, Institute of Molecular and Genomic Medicine, National Health Research Institutes, Zhunan, Taiwan
2002/08 – 2004/12
Member of the Professional Staff, Biology Division, California Institute of Technology, Pasadena, California, USA
2001/08 – 2002/07
Director, Transcription Factor Center, Beckman Institute,, California Institute of Technology, Pasadena, California, USA
1996/08 – 2001/07
Research Associate, Division of Medical Research, Stowers Institute for Medical Research, Missouri, USA
1995/08 – 2001/07
Senior Research Fellow, Biology Division, California Institute of Technology, Pasadena, California, USA
1992/08 – 1995/07
Research Fellow, Biology Division, California Institute of Technology, Pasadena, California, USA
1989/08 – 1992/07
Teaching Assistant, Institute of Microbiology and Immunology, National Yang-Ming Medical College, Taipei, Taiwan
Dr. Yuh has been actively involved in researching gene regulation during both development and carcinogenesis. She received her Ph.D. from the Institute of Microbiology and Immunology at National Yang-Ming Medical College in Taiwan in 1992. During her early career, Dr. Yuh identified the second enhancer (enhancer II) of the hepatitis B virus and discovered its mechanism of action with the core promoter of the HBV, which led to her publishing five international papers and one book chapter in this field.
Later, Dr. Yuh gained significant experience in systematic approaches to embryonic development and Gene Regulatory Networks (GRNs) under the supervision of Dr. Eric Davidson at the California Institute of Technology (Caltech). She also participated in establishing the Endomesoderm Gene Regulatory Network in sea urchin. Before joining NHRI, she published seventeen scientific high-impact papers and three book chapters.
In 2004, Dr. Yuh was recruited as an Associate Investigator by the DMGM of NHRI. She began using zebrafish as a model organism to decode the embryonic gene regulatory networks, and published six papers in international well-known journals such as Developmental Biology, BMC Developmental Biology, and Birth Defects Research Part C. She used a web-enabled GRN modeling tool (BioTapestry) to build an integrated model of the Endomesoderm Gene Regulatory Network in zebrafish, and functionally dissected the important subcircuits in the endoderm networks using systematic approaches. She identified several interesting functional motifs that are important building blocks in zebrafish developmental GRNs.
Dr. Yuh’s research also extends to translational research, where she investigates the genes and pathways involved in the development of cancer. She initiated the systematic analysis of hepatocellular carcinoma (HCC) in mouse models and established transgenic zebrafish models. From these models, she identified five critical oncogenes from mouse models, verified them using human HCC specimens, and confirmed them in transgenic zebrafish. Dr. Yuh studied the mechanism of ribose-5-phosphate isomerase A (RPIA) in human hepatocellular carcinoma (HCC) and colorectal cancer. She also studied alpha-mannosidase 1A1, 1A2, and 1B1 as well as the down-regulation of alpha-mannosidase 1C1 during hepatocarcinogenesis.
Currently, Dr. Yuh’s research focuses on the role of dysregulated metabolism in hepatocarcinogenesis, specifically the coordination of glycolysis, the pentose phosphate pathway (PPP), and inflammation in driving tumor promotion. The study identified that PFKL, a rate-limiting enzyme in glycolysis, stabilizes RPIA, a key enzyme in the PPP, by inhibiting ubiquitination/proteasome. The pro-inflammatory and tumor cytokine interleukin 6 (IL6) induces PFKL through dual pathways, which stabilizes the PFKL protein and increases the transcription of AMPK and PFKL. Inhibiting PFKL, AMPK, and STAT3 genetically or pharmacologically can reduce glycolysis, ATP production, resulting in the reduction of hepatoma cell proliferation and migration. The study provides evidence from clinical data, cell culture, molecular and protein analysis, combined with zebrafish in vivo models, to demonstrate the significance of the PFKL, AMPK, RPIA, and PKM2 co-localization in the Glycolytic body (G-body) during chronic inflammation and the potential therapeutic means for NAFLD and HCC by targeting the STAT3/AMPK/PFKL axis.
Dr. Yuh’s research has also focused on finding more effective and safe drugs for anti-HCC. She has used liver-specific fluorescence transgenic fish embryos to test the effects of drugs such as 420S1 and Sorafenib on liver RFP intensity and size, with promising results. Additionally, she has developed a drug screening platform to develop novel target drugs for anti-cancer and congenital myopathy. Through collaborations with biotechnology companies, she has explored the application and development of natural health foods, including oligo-fucoidan, Carassius auratus complex formula (CACF), and glutamic acid chelated cobalt (GACC), in anti-liver cancer and anti-lipid accumulation, and has worked to discover the underlying mechanisms.
In addition to her research, Dr. Yuh has been actively involved in teaching and promoting Systems Biology in Taiwan. She has taught Gene Regulatory Network and Systems Biology courses at National Tsing-Hua University, National Chiao Tung University, and National China Medical College.
HIGHLIGHTS OF RECENT RESEARCH
Endoderm Gene Regulatory Networks in zebrafish
Many studies on the development of the liver in different model organisms have demonstrated that the mechanism of hepatogenesis is conserved in vertebrates. The identification of the genes and regulatory pathways involved in liver formation provides a basis for the diagnosis of liver diseases and therapeutic interventions. Liver derived from endoderm, Dr. Yuh therefore study the Gene Regulatory Networks (GRNs) of endoderm in order to understand the molecular mechanism of liver specific genes’ expression, eventually to derive some medical implications. Dr. Yuh has established the gene regulatory networks for zebrafish embryogenesis, functional dissecting the important subcircuits in the endoderm networks and published five papers.
Identification of the common regulators for hepatocellular carcinoma induced by hepatitis B virus X antigen in a mouse model
Hepatitis B virus X antigen plays an important role in the development of human hepatocellular carcinoma (HCC). The key regulators controlling the temporal downstream gene expression for HCC progression remains unknown. Dr. Yuh took advantage of systems biology approach and analyzed the microarray data of the HBx transgenic mouse, identified five common regulator genes: EDN1, BMP7, BMP4, SPIB and SRC. Up-regulation of the common regulators was validated in the other independent HBx transgenic mouse lines. Using the human HCC samples, Dr. Yuh found EDN1, BMP4 and BMP7 were up-regulated in cirrhosis; BMP4, BMP7, and SRC were further up-regulated in hepatocellular or cholangiocellular carcinoma samples. Overexpression of the common regulators increases the cell viability, promotes migration and invasiveness, and enhances the colony formation ability in Hep3B cells. The validation of the gene expressions in the liver cancer of human patients and their cellular function assays suggests that the identified common regulators may serve as useful molecular targets for the early-stage diagnosis or therapy for HCC. The results have been publishing on Carcinogenesis. 2012 Jan; 33(1):209-219
Liver-specific expressions of HBx and src in the p53 mutant trigger hepatocarcinogenesis in zebrafish
Hepatocarcinogenesis is a multistep process that starts from fatty liver and transitions to fibrosis and, finally, into cancer. Many etiological factors, including hepatitis B virus X antigen (HBx) and p53 mutations, have been implicated in hepatocarcinogenesis. However, potential synergistic effects between these two factors and the underlying mechanisms by which they promote hepatocarcinogenesis are still unclear. Dr. Yuh show that the synergistic action of HBx and p53 mutation triggers progressive hepatocellular carcinoma (HCC) formation via src activation in zebrafish. Liver-specific expression of HBx in wild-type zebrafish caused steatosis, fibrosis and glycogen accumulation. However, the induction of tumorigenesis by HBx was only observed in p53 mutant fish and occurred in association with the up-regulation and activation of the src tyrosine kinase pathway. Furthermore, the overexpression of src in p53 mutant zebrafish also caused hyperplasia, HCC, and sarcomatoid HCC, which were accompanied by increased levels of the signaling proteins p-erk, p-akt, myc, jnk1 and vegf. Increased expression levels of lipogenic factors and the genes involved in lipid metabolism and glycogen storage were detected during the early stages of hepatocarcinogenesis in the HBx and src transgenic zebrafish. The up-regulation of genes involved in cell cycle regulation, tumor progression and other molecular hallmarks of human liver cancer were found at later stages in both HBx and src transgenic, p53 mutant zebrafish. Dr. Yuh’s study demonstrates that HBx and src overexpression induced hepatocarcinogenesis in p53 mutant zebrafish. This phenomenon mimics human HCC formation and provides potential in vivo platforms for drug screening for therapies for human liver cancer. The results have been publishing on PLoS One 2013 Oct 9; 8(10):e76951.
HONORS & AWARDS
2018 Liver Disease Prevention Research Foundation Fellowship
2015 Liver Disease Prevention Research Foundation Fellowship
2014 Liver Disease Prevention Research Foundation Fellowship
2012 Liver Disease Prevention Research Foundation Fellowship
1995 Biology Divisional Fellowship, California Institute of Technology
1994 Gordon Ross Fellowship, California Institute of Technology
1993 Procter and Gamble Fellowship, California Institute of Technology
1991 First prize scholarship from Wang Ming-Ning Memorial Foundation, Taiwan
1984-1987 Ranked-First Scholarship Award, Fu-Jen Catholic University, Taiwan
- Hou CY, Ma CY, Lin YR, Huang CL, Wang HD*, Yuh CH*, WNK1–OSR1 Signaling Regulates Angiogenesis-Mediated Metastasis towards Developing a Combinatorial Anti-Cancer Strategy. International Journal of Molecular Sciences, 2022, 23(20), 12100
- Hou CY, Ma CY, Yuh CH*, WNK1 kinase signaling in metastasis and angiogenesis. Cellular Signaling, 2022 Aug;96:110371
- Lin HD, Ma N, Yuh CH*, Chen SC*, Low concentrations of 4-ABP promote liver carcinogenesis in human liver cells and a zebrafish model. Journal of Hazardous Materials, 2022 Feb 5;423(Pt A):126954
- Hsu PJ, Wang HD, Tseng YC, Pan SW, Sampurna BP, Jong YJ, Yuh CH*, L-Carnitine Ameliorates Congenital Myopathy in a Tropomyosin 3 de novo Mutation Transgenic Zebrafish. Journal of Biomedical Science, 2021, Jan 12;28(1):8
- Wu SY, Yang WY, Cheng CC, Lin KH, Sampurna BP, Chan SM, Yuh CH*, Low molecular weight fucoidan inhibits hepatocarcinogenesis and nonalcoholic fatty liver disease in zebrafish via ASGR/STAT3/HNF4A signaling. Clinical and Translational Medicine, 2020 Dec 21;10(8):e252
- Sie ZL, Li RY, Sampurna BP, Hsu PJ, Liu SC, Wang HD, Huang CL*, Yuh CH*, WNK1 Kinase Stimulates Angiogenesis to Promote Tumor Growth and Metastasis, Cancers, 2020 Mar 2;12(3).
- Yang WY, Rao PS, Luo YC, Lin HK, Huang SH, Yang JM*, Yuh CH*, Omics-based Investigation of Diet-induced Obesity Synergized with HBx, Src, and p53 Mutation Accelerating Hepatocarcinogenesis in Zebrafish Model, Cancers 2019 Nov., 11(12):1899
- Lin HS, Huang YL, Wang YS, Hsiao E, Hsu TA, Shiao HY, Jiaang WT, Sampurna BP, Lin KH, Wu MS, Lai GM, Yuh CH*, Identification of Novel Anti-Liver Cancer Small Molecules with Better Therapeutic Index than Sorafenib via Zebrafish Drug Screening Platform. Cancers (Basel). 2019 May 28;11(6). pii: E739
- Chou YT, Chen LY, Tsai SL, Tu HC, Lu JW, Ciou SC, Wang HD*, Yuh CH*, Ribose-5-Phosphate Isomerase A (RPIA) Overexpression Promotes Liver Cancer Development in Transgenic Zebrafish via activation of ERK and β-catenin pathways, Carcinogenesis, 2019 May; 40(3): 461–473.
- Chou YT, Jiang JK, Yang MH, Lu JW, Lin HK, Wang HD*, Yuh CH*, Identification of a non-canonical function for ribose-5-phosphate isomerase A promotes colorectal cancer formation by stabilizing and activating β-catenin via a novel C-terminal domain, PLoS Biology, 2018 Jan 16;16(1):e2003714
- 王雯靜, 曾琳蘆 ,鄭欣弘, 喻秋華/抑制胃癌腫瘤生長或判斷胃癌腫瘤生長階段之方法/110104309/2021-02-04/Taiwan/NHRI-EX109-10919B1
- Wen-Ching Wang, Lin-Lu Tseng, Hsin-Hung Cheng, Chiou-Hwa Yuh /METHOD FOR INHIBITING TUMOR PROGRESSION OR DETERMINING TUMOR PROGRESSION STATE IN GASTRIC CANCER/17-074,647/2020-10-20/USA/NHRI-EX109-10919B1
- Horng-Dar Wang, Chiou-Hwa Yuh, Shih-Ci Ciou, Yu-Ting Chou/Method for inducing cancer cell apoptosis or inhibiting the cancer cell migration/US 8785412 B2/2014-07-22~2031-10-25/USA
- 汪宏達、喻秋華、蕭詠駿、邱于庭/早期階段檢測肝癌及預測肝癌轉移之方法/I 440855/2014-06-11~2031-07-26/Taiwan
- Horng-Dar Wang, Chiou-Hwa Yuh, Yung-Chun Hsiao, Yu-Ting Chou/Method for early diagnosis of liver cancer and prediction of metastasis/US 8628920 B2/2014-01-14~2031-09-13/USA
- 汪宏達、喻秋華、邱士齊、邱于庭/核酮糖五磷酸異構酶A促進癌細胞凋亡或抑制癌細胞轉移的方法/I 418361/2013-12-11~2031-04-07/Taiwan