Li-Rung Huang, Ph.D.
Institute of Molecular and Genomic Medicine
Ph.D., Microbiology, National Taiwan University (2007)
M.S. Immunology, National Taiwan University (1998)
B.V.M. Veterinary Medicine, National Chung Hsing University (1996)
1998-2000 Research assistant, laboratory of Dr. John T. Kung, Institute of Molecular Biology, Academia Sinica: CD8+ T cell memory
2007-2008 Postdoctoral fellow, laboratory of Dr. Pei-Jer Chen, Graduate Institute of Clinical Medicine, National Taiwan University: HBV animal models and HBV persistence
2008-2013 Postdoctoral fellow, laboratory of Dr. Percy A. Knolle, Institute of Molecular Medicine and Experimental Immunology, University of Bonn: Liver immunology focusing on cell-cell interaction of intrahepatic myeloid cells and CD8+ T cells
2013- present Assistant Investigator, Institute of Molecular and Genomic Medicine, National Health Research Institute
Cancers are among the leading causes of death worldwide and account for 8.2 million deaths in 2012 based on the statistical analysis from WHO. Common used therapeutic strategies at present are designed to remove or shrink the tumor mass through surgery or induction of tumor death by nonspecific cytotoxic agents. During the past two decades, due to the better understanding of cancer pathogenesis, targeted therapy and immunotherapy have been extensively developed and utilized in cancer treatment. In principle, immunotherapy aims to generate effective T cell response for direct killing of tumor cells and induce long-term immune surveillance against cancers. The antigen specificity, life span and effector functions of the resultant T cells from immunotherapies may determine their efficacy. Moreover, the inhibitory mechanisms in tumor microenvironment may also influence the efficacy of the cancer immunotherapy. Dr. Huang has profound experiences working on immune cell interactions in the liver microenvironment and also on T-cell engineering and currently is developing immunotherapies for treatment of cancers based on these well-established immunological knowledge and technologies in the laboratory.
Immunotherapy for CHB and malignancies
During chronic viral infections or malignancies, there are usually monoclonal T cell response detected and most of the Ag-specific T cells undergo exhaustion or apoptosis rapidly after activation. T-cell engineering to introduce genes encoding viral or tumor antigen specific T cell receptors (TCRs) with high avidity or chimeric antigen receptors (CARs) with unique Ag recognition bypassing MHC restriction into activated CD8+ T cells for adoptive cell transfer (ACT) for treatment of malignancies or chronic hepatitis B has been developed and proved to elicit significant clinical responses in patients with melanoma or B-cell leukemia or HBV clearance in preclinical mouse model. Up to now, in addition to TCR and CAR genes, genes encoding co-stimulatory molecules to prevent apoptosis or enhance survival, chemokine receptors to promote T-cell homing and Th1 cytokines to induce inflammation have been used in T-cell engineering for ACT. We aim to study how these effector T cells control its lifespan intrinsically upon stimulation of cognate antigen and co-stimulation/co-inhibition in the tumor or liver microenvironment and how T-cell exhaustion is induced in these intratumoral or intrahepatic T cells. We hypothesize that activated T cells would adjust their metabolic status upon encounter with the cognate antigen, proper co-stimulatory signals to facilitate their aerobic glycolysis, protein translation and lipid synthesis, which suppress apoptosis and therefore prolong the life span of the T cells under regular inflammatory condition in secondary lymphoid organs. However, when entering tumor/liver microenvironment and encountering inhibitory mechanisms, the activated T cells no longer maintain their metabolic status and switch on/off certain metabolic regulation, which promotes T-cell exhaustion. We now are investigating the detailed mechanisms responsible for regulating T-cell survival in the tumor/liver and apply the acquired knowledge in T-cell engineering of CAR T cells for treatment of malignancies and chronic HBV infections
Metabolic reprograming of myeloid cells during tumor progression and during inflammation
Myeloid cells have been shown to be involved in regulation of immune system as well as in promotion of tumor angiogenesis and metastasis. Dr. Huang’s lab is currently investigating the metabolic status of myeloid-derived suppressor cells (MDSCs) and inflammatory monocytes/macrophages and expecting to elucidate the underlying mechanisms responsible for the induction and maintenance of these myeloid cells during tumor progression or inflammation, which may benefit the design of therapeutic strategies for treatment of clinical metastatic disease, Dr. Huang’s lab has found that glycolytic pathway played an important role in maintenance of the cell number of MDSCs in tumor-bearing individual. Specific glycolytic enzymes highly up-regulated during tumor progression are under evaluation for their potential as drug targets. The ultimate goal of Dr. Huang’s lab is to develop therapeutic strategies for curing malignancies through combining the modality able to relieve the immunosuppression induced by MDSCs and immunotherapy e.g. cancer vaccines or ACT.
HONORS & AWARDS
1998 Shen Fong-Wen Award for excellent master student.
2007 Award for excellent Ph.D thesis, Liver Disease Prevention &Treatment Research Foundation.
2007 The 17th Annual Wang Ming-Ning Award for medical Ph.D thesis
2011 BONFOR research prize, Research Commission of Medical School of University of Bonn, Germany
- Liu, Y.T §., Tseng, T.C. §, Soong, R.S. §, Peng, C.Y., Cheng, Y.H., Huang, S.F., Chuang, T.H., Kao, J.H. and Huang, L.R.* A novel spontaneous hepatocellular carcinoma mouse model for studying T-cell exhaustion in the tumor microenvironment. J Immunother Cancer. 2018 Dec 7;6(1):144. doi: 10.1186/s40425-018-0462-3. *Corresponding author. (§equal contribution)
- Tseng, T.C., Huang, L.R.* Immunopathogenesis of hepatitis B virus. The Journal of Infectious Diseases, 2017;216(S8):S765-70 Review article. *Corresponding author. Review article
- Jian, S.L., Chen, W.W., Su, Y.C., Su, Y.W., Chuang, T.H., Hsu, S.C. and Huang, L.R.* Glycolysis regulates the expansion of myeloid-derived suppressor cells in tumor-bearing hosts through prevention of ROS-mediated apoptosis. Cell Death & Disease, 2017, 8, e2779; doi:10.1038/cddis.2017.192. *Corresponding author.
- Knolle, P.A., Böttcher, J., Huang, L.R. The role of hepatic immune regulation in systemic immunity to viral infection. Med. Microbiol. Immunol. 204:21-7, 2015. Review article
- Huang, L.R., Wohlleber, D., Reisinger, F., Jenne, C.N., Cheng, R.L., Abdullah, Z., Schildberg, F.A., Odenthal, M., Dienes, H.P., van Rooijen, N., Schmitt, E., Garbi, N., Croft, M., Kurts, C., Kubes, P., Protzer, U., Heikenwalder, M. and Knolle, P.A. Intrahepatic myeloid-cell aggregates enable local proliferation of CD8 T cells and successful immunotherapy against chronic viral liver infection. Nat Immunol. 14:574-583, 2013
- Krebs, K., Böttinger, N., Huang, L.R., Chmielewski, M., Arzberger, S., Gasteiger, G., Jäger, C., Schmitt, E., Bohne, F., Aichler, M., Uckert, W., Abken, H., Heikenwalder, M., Knolle, P.A. and Protzer, U., T cells expressing a chimeric antigen receptor that binds Hepatitis B virus envelop proteins control virus replication in mice. Gastroenterology, 145:456-65, 2013
- Huang, L.R., Gäbel, Y.A., Graf, S., Arzberger, S., Kurts, C., Heikenwalder, M., Knolle, P.A., and Protzer, U. Transfer of HBV genomes using low doses of adenovirus vectors leads to persistent infection in immune competent mice, Gastroenterology 142:1447-50, 2012
- Lin, Y. J.*, Huang, L.R.*, Yang, H.C., Tzeng, H. T., Hsu, P.N., Chen, P.J. and Chen D.S., Hepatitis B Virus Core Antigen Determines Viral Persistence in a C57BL/6 Mouse Model. Proc Natl Acad Sci U S A. 107:9340-5, 2010 (* equal contribution)
- Huang, L.R., Wu, H.L., Chen, P.J. and Chen, D.S., An immunocompetent mouse model for the tolerance of human chronic hepatitis B virus infection. Proc Natl Acad Sci U S A. 103: 17862-67, 2006
- Huang, L.R., Chen, F.L., Chen, Y.T., Lin, Y.M. and Kung, J.T. Potent induction of long-term CD8+ T cell memory by short-term IL-4 exposure during T cell receptor stimulation. Proc Natl Acad Sci U S A. 97: 3406-11, 2000
- Method using heat shock protein inhibitor for treating hepatitis and hepatoma, Hui-Ching Wang, Ting-Chung Yen, Li-Rung Huang, Patent No.: US9687499B2, Patent date: Jun. 27, 2017
- 熱休克蛋白抑制劑用於製備治療B型肝炎或肝癌之醫藥組合物的用途。王慧菁，顏廷忠，黃麗蓉, 103021TWI , Pending, 2014
- Vaccination strategies, Percy A. Knolle, Mathias Heikenwalder, Ulrike Protzer, Li-Rung Huang, Patent No.: CN105451766 A, Publication date: Mar 30, 2016
- Vaccination strategies, Percy A. Knolle, Li-Rung Huang, Mathias Heikenwalder, Ulrike Protzer, Patent No.: US20160008460 A1, Publication date: Jan 14, 2016
- Vaccination strategy, Percy A. Knolle, Ulrike Protzer, Mathias Heikenwalder, Li-Rung Huang, Patent No.: EP2958587 A1, Publication date: Dec 30, 2015
- Vaccination strategies, Percy A. Knolle, Mathias Heikenwalder, Ulrike Protzer, Li-Rung Huang, Patent No.: CA2902362 A1, Publication date: Aug 28, 2014
- Vaccination strategies, Percy A. Knolle, Mathias Heikenwalder, Ulrike Protzer, Li-Rung Huang, Patent No.: WO2014128305 A1, Publication date: Aug 28, 2014
- Recombinant plasmid and method for expressing hepatitis B viral antigens and virions in vivo, Pei-Jer Chen, Li-Rung Huang, Hui-Lin Wu and Ding-Shinn Chen, Patent No.: US 7,452,696 B2, Patent date: Nov. 18, 2008
- 一種用以於活體中表現b型肝炎病毒抗原的重組質體及方法。 陳培哲, 黃麗蓉，吳慧琳及陳定信, Patent No.: TW 098107943, Patent date: Dec. 20, 2005