Dr. Ting-Fen Tsai

Joint Investigator
Institute of Molecular and Genomic Medicine
tftsai@ym.edu.tw

EDUCATION

Ph.D., Microbiology and Immunology, National Yang-Ming University, Taipei, Taiwan (1995)
M.S., Microbiology and Immunology, National Yang-Ming University, Taipei, Taiwan (1987)
B.S., Biology, Tunghai University, Taichung, Taiwan (1985)

PROFESSIONAL EXPERIENCES

1995-1999 Postdoctoral fellow, Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX USA

1995-1999 Associate, Howard Hughes Medical Institute, Baylor College of Medicine, Houston, TX, USA

1999-2005 Assistant Professor, Department of Life Sciences and Institute of Genome Sciences, National Yang-Ming University, Taipei, Taiwan

2006-2009 Associate Professor, Department of Life Sciences and Institute of Genome Sciences, National Yang-Ming University, Taipei, Taiwan

2004-2008 Joint Assistant Investigator, Institute of Molecular and Genomic Medicine, National Health Research Institute, Zhunan, Miaoli County, Taiwan

2009-2011 Adjunct Associate Investigator, Institute of Molecular and Genomic Medicine, National Health Research Institute, Zhunan, Miaoli County, Taiwan

2001-2010 Adjunct Associate Investigator, Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan

2011-2012 Adjunct Investigator, Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan

2010-2012 Chair, Institutional Animal Care and Use Committee (IACUC) of National Yang-Ming University, Taipei, Taiwan

2012-2015 Director, Department of Life Sciences and Institute of Genome Sciences, National Yang-Ming University, Taipei, Taiwan

2010-present Professor, Department of Life Sciences and Institute of Genome Sciences, National Yang-Ming University, Taipei, Taiwan

2012-present Joint Investigator, Institute of Molecular and Genomic Medicine, National Health Research Institute, Zhunan, Miaoli County, Taiwan

RESEARCH INTERESTS

The long-term objective of Dr. Tsai’s research interest is to apply mouse genetics approach to elucidate basic molecular and biochemical pathways that regulate mammalian development and homeostasis, and to apply this to the development of new prevention and therapeutic agents for human disorders resulting from the dysregulation of these pathways. A common theme is to take an approach involving the flow of information from the study of human cancers and genetic diseases, to the generation and modeling of human diseases in genetically modified mice, to the testing of hypotheses and evaluation of the phenotypic consequences of gain-of-function of transgenes and/or loss-of-function of endogenous genes, and finally, to the development of treatment protocols using these mouse models.

Dr. Tsai’s lab has contributed to the characterization of a longevity candidate gene, Cisd2, which is located within the longevity region on human chromosome 4q. Using a mouse genetics approach, the lab had demonstrated for the first time that Cisd2 is involved in mammalian lifespan control. Cisd2 deficiency drives premature aging and causes mitochondria-mediated defects in mice. Dr. Tsai’s lab effectively links Cisd2 gene function, mitochondrial integrity and aging in mammals. Furthermore, Dr. Tsai’s group demonstrated that a persistent level of Cisd2 extends healthy lifespan and delays aging in mice. Current studies are focused on (1) exploring the possibility of drug-stimulated Cisd2 expression in mammals; (2) investigating the molecular mechanism underlying the control of lifespan by Cisd2 in mammals; (3) dissect the primary and secondary effects of Cisd2 on phenotypes using tissue-specific knockout mice; and (4) examining the Cisd2 expression levels in various human populations during the aging process, and specifically to compare gene activity and/or protein function between normal populations and long-lived centenarian groups.

Dr. Tsai’s lab is also focused on the study of cancers and cell cycle dysregulation under in vivo physiological condition with particular emphasis on the hepatocellular carcinoma, liver regeneration and liver pathogenesis in mice. Examples of current projects are (1) unraveling the effects of HBV gene products, e.g. X protein, mutant surface antigens, on liver pathogenesis and cancer development; (2) investigating the haplo-insufficient effects of Cisd2 on HCC development in Cisd2 transgenic and knockout mice; (3) developing a platform by using mouse models established in the lab for evaluating and/or screening of chemoprevention and therapeutic agents.

HIGHLIGHTS OF RECENT RESEARCH

CISD2 mediates life span in mammals

CISD2 gene is located within the candidate region on chromosome 4q where a genetic component for human longevity has been mapped. Dr. Tsai’s lab found that mouse Cisd2 deficiency drives premature aging and causes mitochondria-mediated defects in mice (G&D 2009). Interestingly, an age-dependent decrease in mouse Cisd2 expression has been detected during normal aging. Furthermore, Dr. Tsai’s lab demonstrated that a persistent level of Cisd2 achieved by transgenic expression in mice extends their median and maximum lifespan without any apparent deleterious side effects. Cisd2 also ameliorates age-associated degeneration of the skin, skeletal muscles and neurons. Moreover, Cisd2 protects mitochondria from age-associated damage and functional decline as well as attenuating the age-associated reduction in whole-body energy metabolism. These results suggest that Cisd2 is a fundamentally important regulator of lifespan, and provide an experimental basis for exploring the candidacy of CISD2 in human longevity (HMG, 2012).

Fig 1 - TFTemptyFig 2 - TFT

HONORS & AWARD

2010 Award of Far Eastern Y. Z. Hsu Science and Technology Memorial Foundation
2009-2012 Distinguished Research Award of National Science Council
2007-2011 Distinguished Research Award of National Yang-Ming University
2011-2013 Distinguished Research Award of National Yang-Ming University
2013-2015 Distinguished Research Award of National Yang-Ming University
2015-2017 Distinguished Research Award of National Yang-Ming University

Societies

The American Society of Human Genetics (ASHG) member
American Association for Cancer Research (AACR) member
Asian Association of Aging Research (AAAR) member
Asia-Pacific Developmental Biology Network (APDBN) member
Taiwan Society of Developmental Biology (Life Member)
Neuroscience Society of Taiwan (Life Member)
Taiwan Society for Mitochondrial Research and Medicine (TSMRM) member
Taiwan Association for the Study of the Liver (TASL) member
The Chinese Taipei Society of Laboratory Animal Sciences (Life Member)

Public Committee Member

2002-present, Advisory Committee, Transgenic Core Facility, Institute of Molecular Biology, Academia Sinica.
2006-present, User’s Committee, (A4) Transgenic Mouse Models Core, National Science Council.
2012-present, User’s Committee, (A8) Genetic Engineered Murine Model Services (GEMMS), National Science Council.
2003-2009, User’s Committee, (A1) National Mouse Mutagenesis Program Core Facility, National Research Program for Genomic Medicine.
2008-2012, User’s Committee, (A7) Taiwan Mouse Clinic (TMC) – National Phenotyping Center, National Science Council.

SELECTED PUBLICATIONS

    1. Teng YC, Shen ZQ, Kao CH, Tsai TF. HCC mouse models: HBV-associated hepatocarcinogenesis and haploinsufficient tumor suppressor genes. World Journal of Gastroenterology 2016, 22(1):300-325.
    2. Wang CH, Chen YF, Wu CY, Wu PC, Huang YL, Kao CH, Lin CH, Kao LS, Tsai TF, Wei YH. Cisd2 modulates differentiation and functioning of adipocytes by regulating intracellular Ca2+ homeostasis. Human Molecular Genetics 2014, 23(18):4770-4785.
    3. Wu CY, Chen YF, Wang CH, Kao CH, Zhuang HW, Chen CC, Chen LK, Kirby R, Wei YH, Tsai SF, Tsai TF. A persistent level of Cisd2 extends healthy lifespan and delays aging in mice. Human Molecular Genetics 2012, 21(18):3956-3968.
    4. Lin HC, Chen YF, Hsu WH, Yang CW, Kao CH, Tsai TF. Resveratrol helps recovery from fatty liver and protects against hepatocellular carcinoma induced by hepatitis B virus X protein in a mouse model. Cancer Prevention Research 2012, 5(7):952-962.
    5. Chen YF, Kao CH, Chen YT, Wang CH, Wu CY, Tsai CY, Liu FC, Yang CW, Wei YH, Hsu MT, Tsai SF, Tsai TF. Cisd2 deficiency drives premature aging and causes mitochondria-mediated defects in mice. Genes & Development 2009, 23:1183-1194 (Cover Story).
    6. Li CC, Chu HY, Yang CW, Chou CK, Tsai TF. Aurora-A overexpression in mouse liver causes p53-dependent premitotic arrest during liver regeneration. Molecular Cancer Research 2009, 7(5):678-688 (Highlight Article).
    7. Tsai CY, Chou CK, Yang CW, Lai YC, Liang CC, Chen CM, Tsai TF. Hurp deficiency in mice leads to female infertility caused by an implantation defect. Journal of Biological Chemistry 2008, 283(39):26302-26306.
    8. Wu YF, Fu SL, Kao CH, Yang CW, Lin CH, Hsu MT, Tsai TF. Chemopreventive effect of silymarin on liver pathology in HBV X protein transgenic mice. Cancer Research 2008, 68(6): 2033-2042 (Highlight Article).
    9. Bressler J, Tsai TF, Wu MY, Tsai SF, Ramirez MA, Armstrong D, Beaudet AL. The SNRPN promoter is not required for genomic imprinting of the Prader-Willi/Angelman domain in mouse. Nature Genetics 2001, 28:232-239.
    10. Tsai TF, Armstrong D, Beaudet AL. Necdin deficient mice do not show lethality or the obesity and infertility of Prader-Willi syndrome. Nature Genetics 1999, 22:15-16.

PATENT

  1. Tsai TF, Chen YF, Tsai SF, and Chen YT. CISD2-Konckout Mice and Uses Thereof. Application type: Provisional United States Patent 20080104719. Application Number 11/866374. Filing date Oct. 2, 2007. Publication date May 1, 2008. United States Patent.
  2. Tsai TF, Chen YF, Wu CY, Wang CH, and Tsai SF. Methods and compositions for the treatment and prevention of aging-associated conditions. Application type: Provisional United States Patent. Docket number N023-0003USP1. Filing date Nov. 3, 2011. United States Patent.
  3. Tsai TF, Chen YF, Wu CY, Wang CH, and Tsai SF. Filing date Oct. 2012. Methods and compositions for the treatment and prevention of aging-associated conditions. People’s Republic of China; Docket number 27713.
  4. Tsai TF, Chen YF, Wu CY, Wang CH, and Tsai SF. Filing date Oct. 2012. Methods and compositions for the prevention of aging-associated skin conditions. Taiwan; Docket number 2011RDPA013.

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