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.