President & Secretary-general
The 18th - Current
Director / Distinguished Investigator Institute of Molecular and Genomic Medicine
Lo, S. H
EDUCATION
1993 Ph.D., Cell and Developmental Biology at Harvard Medical School, Harvard University, Cambridge, MA, USA
1986 BS, Department of Agricultural Chemistry. National Taiwan University, Taipei, Taiwan
PROFESSIONAL EXPERIENCES
2024/10 present Distinguished Investigator & Director, Institute of Molecular and Genomic Medicine, National Heath Research Institutes, Taiwan
2024- present YuShan Scholar, Cancer and Immunology Research Center, National Yang Ming Chiao Tung University, Taiwan
2024- present Professor Emeritus, Department of Biochemistry and Molecular Medicine, University of California-Davis, Davis, CA
2023/3-5 Visiting scholar. Institute of Biomedical Sciences, Academia Sinica, Taiwan
2013/11-12 Visiting scholar. Institute of Biological Chemistry, Academia Sinica, Taiwan
2009- 2024 Professor, Department of Biochemistry and Molecular Medicine, University of California-Davis, Davis, CA
2007/5-8 Visiting scholar. Department of Molecular Medicine, Max Planck Institute for Biochemistry, Martinsreid. Germany
2007-2009 Associate Professor, Center for Tissue Regeneration and Repair, Department of Biochemistry and Molecular Medicine, University of California-Davis, Davis, CA
2005-2007 Associate Professor, Center for Tissue Regeneration and Repair, Department of Orthopaedic Surgery, University of California Davis, Davis, CA
2005-2024 Member of the graduate group of the Comparative Pathology (now GGIP) University of California-Davis
2003-2024 Member of the graduate group of Pharmacology and Toxicology University of California-Davis
1998-2024 Member of the Cancer Center, University of California-Davis
1998-2024 Member of the graduate group of Cell and Developmental Biology (now BMCDB) University of California-Davis
1998-2005 Assistant Professor, Center for Tissue Regeneration and Repair, Department of Orthopaedic Surgery, University of California Davis-Davis, CA, USA
1994-1998 Postdoctoral Fellow, Howard Hughes Medical Institute, Department of Molecular Genetics and Cell Biology, The University of Chicago, IL, USA
RESEARCH INTERESTS
My overall research interest is to understand how cells communicate with each other and with their environments. These communications include both outside-in and inside-out signals and are essential for numerous biological events. In a multicellular organism, cell-cell interactions and cell-matrix interactions play critical roles in cellular communication. Focal adhesions are integrin-mediated junctions that attach various cell types to their underlying substratum. They are signal transduction organelles mediating diverse biological processes, including cell proliferation, attachment, migration, death, polarization, homeostasis, and differentiation. As such, focal adhesion dysfunction is known to have profound repercussions in embryogenesis, tissue development and repair, as well as in many pathological conditions, including various forms of cancer and kidney diseases. My contributions to understanding the focal adhesion tensin family, the DLC1 family, and their associated networks span over 30 years, during which I have participated in nearly all the major breakthroughs in the field (publications listed below: #2, 5, 10, 20, 27, 32, 49, 54, 62, 65). This includes the identification of all four genes of the tensin family (4, 13, 17, 18, 21), in vitro characterization of the molecules (1, 3, 8, 16, 19, 23, 30, 48, 56, 57, 64), functional analyses of knockout/knockin animal models (9, 15, 22, 38, 55, 59, 60, 64), their various roles in cancer or other diseases (7, 11, 12, 28, 31, 33, 35, 39, 40, 43, 45, 47, 50, 51, 52, 53, 58, 63, 67), and the application of nanotechnology for research (34, 41, 42, 44, 61).
In addition to cancer and renal diseases, my recent research program also includes phase separation of focal adhesion proteins. Although previous reports suggest that phase separation of focal adhesion proteins may serve as precursors for focal adhesion assembly, our live cell studies indicate that phase separation of TNS1 is involved in focal adhesion disassembly, and the presence of TNS1 condensates is regulated by mitosis (66). These observations open many new research directions in the field of phase separation in conjunction with focal adhesions, and our model offers an excellent system for these studies.
In my new role at IMGM, we will apply genomic, genetic, and molecular approaches to understand the causes, develop strategies, and ultimately reduce the number of patients or the disease burden in those suffering from common diseases, as well as other understudied diseases in Taiwan. This will involve large teamwork and, more critically, collaboration with patients and experts in relevant fields.
Secretary-general
Li-Rung Huang
學歷
Ph.D., Microbiology, National Taiwan University (2007)
M.S. Immunology, National Taiwan University (1998)
B.V.M. Veterinary Medicine, National Chung Hsing University (1996)
經歷
2021/01 – present
Associate Investigator, Institute of Molecular and Genomic Medicine, National Health Research Institutes
2017/02 – present
Adjunct Assistant professor, Graduate Institute of Clinical Medicine, National Taiwan University, Taipei, Taiwan
2013/04 – 2020/12
Assistant Investigator, Institute of Molecular and Genomic Medicine, National Health Research Institutes
2008/03 – 2013/03
Postdoctoral fellow, Institute of Molecular Medicine and Experimental Immunology, University of Bonn, Germany
2007/02 – 2008/01
Postdoctoral fellow, Graduate Institute of Clinical Medicine, National Taiwan University, Taipei, Taiwan
1998/07 – 2000/06
Research assistant, Institute of Molecular Biology, Academia Sinica, Taipei, Taiwan
研究興趣
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.
榮譽與獲獎
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
2018 Gilead Sciences Research Scholars Program in Liver Disease-Asia