Dr. Hong-Hsing Liu

 

Hong-Hsing Liu, M.D. Ph.D.

Assistant Investigator and Attending Physician
Institute of Molecular and Genomic Medicine
hhliu@nhri.org.tw

EDUCATION

Ph.D., Integrative Biology, The University of Texas Southwestern Medical Center at Dallas (2006)
M.D., School of Medicine, National Taiwan University (1996)

PROFESSIONAL EXPERIENCES

1989-1996      Medical Student, College of Medicine, National Taiwan University, Taiwan.
1996-1998      Army Physician, Compulsory Military Service, Taiwan.
1998-2001      Resident, Pediatrics Department of National Taiwan University Hospital, Taiwan.
2001-2006      Graduate Student, Integrative Biology, Laboratory of Dr. Zhijian Chen, The University of Texas Southwestern Medical Center at Dallas, USA.
2006-2010      Postdoctoral Fellow, Laboratory of Dr. Gary Peltz, Roche Palo Alto/Stanford University, USA.
2010-2012      Pediatric Gastrointestinal Fellow. Taiwan Adventist Hospital/National Taiwan University Hospital, Taiwan.
2011-Now        Attending Physician of Pediatrics, En Chu Kong Hospital, Taiwan.
2012-Now       Assistant Investigator and Attending Physician, Institute of Molecular and Genomic Medicine, National Health Research Institutes, Taiwan

RESEARCH INTERESTS

Dr. Liu’s research interest is to bring personalized medicine into reality with both bioinformatic technology and humanized mouse models. Many diseases are caused by inappropriate immune interactions between environments and hosts. However it is not a simple task to reach a molecular diagnosis for many of them. For example most patients of chronic urticaria cannot find specific antigens that cause their symptoms, let alone specific receptors of lymphocytes that are activated by such antigens. Indeed each individual has a unique set of immune repertoires in response to environmental challenges. These repertoires are created and matured through a series of random events, which make them not only unique but also huge and diverse; even identical twins share few components of immune repertoires. Without doubts establishment of methods to interpret personal immune repertoires would be the first step toward personalized medicine. With recent advances of technology including platforms of next-generation sequencing and easy access to parallel and heterogeneous computations, it is now possible to explore immune repertoires at unprecedented resolutions and efficiency. Nonetheless bioinformatic analyses alone would not be sufficient because experimental elaboration and verification are essential as well. Traditional mouse models are not good enough because murine immune systems are actually very different from human immune systems. A recent innovation is to study human immune reactions on genetically modified mouse models, or humanized mice. Dr. Liu is especially interested in applying the analyses of immune repertoires on humanized mouse models in the hope that an era of personalized medicine will soon come true in the near future.

HIGHLIGHTS OF RECNET RESEARCH

An integrative genomic analysis identifies Bhmt2 as a diet-dependent genetic factor protecting against acetaminophen-induced liver toxicity

fig - HH LiuAcetaminophen-induced liver toxicity is the most frequent precipitating cause of acute liver failure and liver transplant, but contemporary medical practice has mainly focused on patient management after a liver injury has been induced. An integrative genetic, transcriptional, and two-dimensional NMR-based metabolomic analysis performed using multiple inbred mouse strains, along with knowledge-based filtering of these data, identified betaine-homocysteine methyltransferase 2 (Bhmt2) as a diet-dependent genetic factor that affected susceptibility to acetaminophen-induced liver toxicity in mice. Through an effect on methionine and glutathione biosynthesis, Bhmt2 could utilize its substrate (S-methylmethionine [SMM]) to confer protection against acetaminophen-induced injury in vivo. Since SMM is only synthesized in plants, Bhmt2 exerts its beneficial effect in a diet-dependent manner. Identification of Bhmt2 and the affected biosynthetic pathway demonstrates how a novel method of integrative genomic analysis in mice can provide a unique and clinically applicable approach to a major public health problem. The finding was the cover story on Genome Research, Jan. 2010.

HONORS & AWARDS

1996        Honors of Public Service, College of Medicine, National Taiwan University.
2010        The Anesthesia Department Research Award, Stanford University School of Medicine.
2015        The Best Working Partner, En Chu Kong Hospital

SELECTED PUBLICATIONS

  1. Hong-Hsing Liu, Yu-Chen Lin, Chen-Shuan Chung, Kevin Liu, Ya-Hui Chang, Chung-Hsiang Yang, Yun Chen, Yen-Hsuan Ni, and Pi-Feng Chang. Integrated counts of carbohydrate-active protein domains as metabolic readouts to distinguish probiotic biology and human fecal metagenomes. Scientific reports, 9:16836, November 2019.
  1. Chung-Hao Huang, Ya-Hui Chang, Chun-Yu Lin, Wen-Hung Wang, Hui-Chung Kuan, Ya-Ju Hsieh, Yu-Wei Wang, Chung-Hsiang Yang, Jhen-Yan Chiu, Shih-Feng Tsai, Yen-Hsu Chen, and Hong-Hsing Liu. Shared IgG infection signatures vs. hemorrhage-restricted IgA clusters in human dengue: A phenotype of differential class-switch via TGFβ1. Frontiers in Immunology, 8:1726, 2017.
  1. Huey-Huey Chua, Hung-Chieh Chou, Ya-Ling Tung, Bor-Luen Chiang, Chien-Chia Liao, Hong-Hsing Liu, and Yen-Hsuan Ni. Intestinal dysbiosis featuring abundance of ruminococ-cus gnavus associates with allergic diseases in infants. Gastroenterology, 154:154–167, January 2018.
  1. Ya-Hui Chang † , Hui-Chung Kuan † , T. C. Hsieh, K. H. Ma, Chung-Hsiang Yang, Wei-Bin Hsu, Shih-Feng Tsai, Anne Chao, and Hong-Hsing Liu. Network signatures of IgG immune repertoires in hepatitis B associated chronic infection and vaccination responses. Sci Rep, 6:26556, 2016.  † Equal contribution.
  2. Hong-Hsing Liu, Yajing Hu, Ming Zheng, Megan M. Suhoski, Edgar G. Engleman, David L. Dill, Matt Hudnall, Jianmei Wang, Rosanne Spolski, Warren J. Leonard, and Gary Peltz. Cd14 SNPs regulate the innate immune response. Mol Immunol, 51(2):112–127, Jun 2012.
  3. Hong-Hsing Liu † , Peng Lu † , Yingying Guo, Erin Farrell, Xun Zhang, Ming Zheng, Betty Bosano, Zhaomei Zhang, John Allard, Guochun Liao, Siyu Fu, Jinzhi Chen, Kimberly Dolim, Ayako Kuroda, Janet Cheng, Kevin Welch, Yanzhou Liu, Joseph Pease, Steve A. de Keczer, Mo-hammad Masjdizadeh, Jing-Shan Hu, Paul Weller, Tim Garrow, and Gary Peltz. An integrative genomic analysis identified Bhmt2 as a diet-dependent genetic factor against acetaminophen-induced liver toxicity. Genome Res, 20:28–35, 2010.  † Equal contribution
  4. James Schuman, Yuhong Chen, Andrew Podd, Mei Yu, Hong-Hsing Liu, Renren Wen, Zhi-jian J Chen, and Demin Wang. A critical role of TAK1 in B cell receptor-mediated NF-κB activation. Blood, 113(19):4566–4574, May 2009.
  5. Hong-Hsing Liu, Min Xie, Michael D Schneider, and Zhijian J Chen. Essential role of TAK1 in thymocyte development and activation. Proc Natl Acad Sci U S A, 103(31):11677–11682, Aug 2006.
  6. Qinmiao Sun † , Lijun Sun † , Hong-Hsing Liu, Xiang Chen, Rashu B Seth, James Forman, and Zhijian J Chen. The specific and essential role of MAVS in antiviral innate immune responses.Immunity, 24(5):633–642, May 2006.  † Equal contribution.
  7. Hong-Hsing Liu † , Jens Kroll † , Xiaozhong Shi † , Arianna Caprioli † , Claudia Waskow, Keng-Mean Lin, Toru Miyazaki, Hans-Reimer Rodewald, and Thomas N Sato. The BTB-kelch protein KLHL6 is involved in B-lymphocyte antigen receptor signaling and germinal center formation. Mol Cell Biol, 25(19):8531–8540, Oct 2005.  † Equal contribution.

PATENT

1. Liu, H.H., G.A. Peltz, G. Liao, and T.A. Garrow. Compositions and methods for reducing the risk of agent-induced liver toxicity, July 5 2012. US20120172324

Lab Members

劉鴻興醫師實驗室

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