Chung Yuan Christian University (CYCU) aims to combine “Biotechnology” with “lifelong learning for all” as its core development philosophy. The university has established a “Biotechnology and Project Promotion Committee” to actively promote the development of a dedicated “Biotechnology and Project Building.” The Department of Bioscience Technology focuses on the following research areas:
Traditional Chinese Medicine (TCM): Through the application of biotechnology, we can cultivate and develop high-quality health foods, eliminating the need to rely on wild-grown plants from remote locations. The development of health foods represents a significant area of potential within the current biological science and technology landscape. It is also a key development area for our country. Notably, the department boasts several leading professors in the fields of nutrition and food science. We conduct clinical research and collaborate with the Department of Health at Taoyuan General Hospital.
Bioinformatics: Bioinformatics plays a crucial role in deciphering previously unknown DNA sequences, transforming them into meaningful information. Currently, bioinformatics is a rapidly growing field with a significant global talent shortage. Chung Yuan Christian University has strong departments in Information and Computer Engineering, Business Administration, and Mechanical Engineering. Additionally, the university has faculty members with backgrounds in mathematics, chemistry, and chemical engineering, which are relevant fields for bioinformatics. This combination of strengths positions CYCU well to develop a leading bioinformatics program.
The future prospects for our research are:
Dr. Ming-Wei Chao
Dr. Chao was investigating mechanisms responsible for the induction of cytotoxicity and GPT/APRT mutagenicity in nuclear excision repair (NER) deficient CHO cells. To date he has extensively characterized DNA damage, mutagenesis, and the production of ROS in this system. His pre-doctoral and postdoctoral training and experience was in an outstanding laboratory, in which he employed experimental approaches of direct relevance to his current work.
Dr. Wen-Hsiung Chan
Emodin (1,3,8-trihydroxy-6-methylanthraquinone), a major constituent of rhubarb, has a wide range of therapeutic applications. Previous studies have established that emodin induces apoptosis in the inner cell mass and trophectoderm of mouse blastocysts and leads to decreased embryonic development and viability, indicating a role as an injury risk factor for normal embryonic development. However, the mechanisms underlying its hazardous effects have yet to be characterized. In the current study, we further investigated the effects of emodin on oocyte maturation and subsequent pre- and post-implantation development, both in vitro and in vivo. Notably, emodin induced a significant reduction in the rates of oocyte maturation, fertilization, and in vitro embryonic development. Treatment of oocytes with emodin during in vitro maturation (IVM) led to increased resorption of postimplantation embryos and decreased fetal weight. Experiments using an in vivo mouse model disclosed that consumption of drinking water containing 20–40 μM emodin led to decreased oocyte maturation and in vitro fertilization, as well as early embryonic developmental injury. Notably, pretreatment with a caspase-3-specific inhibitor effectively prevented emodin-triggered injury effects, suggesting that impairment of embryo development occurs via a caspase-dependent apoptotic process.
Dr. Ivy Hsu
Oral cancer has becomes the most prominent cancer disease in recent years in Taiwan. The reason is the betel nut chewing habit combing with smoking and alcohol-drinking lifestyle of people results in oral cancer becomes the fastest growth incident cancer amongst other major cancer diseases. In previous studies showed that photosan, haematoporphyrin derivative (HPD), has demonstrated effective PDT results on human head and neck disease studies. To avoid the systemic phototoxic effect of photosan, this study was designed to use a topical photosan-mediated PDT for treatment of DMBA-induced hamster buccal pouch cancerous lesions. DMBA was applied to one of the buccal pouches of hamsters thrice a week for 10 to 12 weeks. Cancerous lesions were induced and proven by histological examination. These DMBA-induced cancerous lesions were used for testing the efficacy of topical photosan-mediated PDT. Before PDT, fluorescence spectroscopy was used to determine when photosan reached its peak level in the lesional epithelial cells after topical application of photosan gel. We found that photosan reached its peak level in cancerous lesions about 13.5 min after topical application of photosan gel. The cancerous lesions in hamsters were then treated with topical photosan-mediated PDT (fluence rate: 600 mW/cm2; light exposure dose 200 J/cm2) using the portable Lumacare 635 nm fiber-guided light device. Visual examination demonstrated that topical photosan-mediated PDT was an applicable treatment modality for DMBA-induced hamster buccal pouch cancerous lesions.
Dr. Ting-Yu Chin To clarify the involvement of autophagy in neuronal differentiation, the effect of rapamycin, an mTOR complex inhibitor, on the dibutyryl cAMP (dbcAMP)-induced differentiation of NG108-15 cells was examined. Treatment of NG108-15 cells with 1 mM dbcAMP resulted in induction of differentiation, including neurite outgrowth and varicosity formation, enhanced voltage-sensitive Ca2+ channel activity and expression of microtubule-associated protein 2, and these effects involved phosphorylation of cAMP-response element binding protein (CREB) and extracellular signal regulated kinase (ERK). Simultaneous application of dbcAMP and rapamycin synergistically increased and accelerated differentiation. mTOR or raptor silencing with siRNA had a similar effect to rapamycin. Rapamycin and silencing of mTOR or raptor evoked autophagy, while blockade of autophagy by addition of 3-methyladenine or beclin 1 or Atg5 silencing prevented the potentiation of differentiation. Silencing of rictor also evokes autophagy, at a level 55% of that induced by raptor silencing and enhancement of differentiation is proportional. Rapamycin also caused increased ATP generation and cell cycle arrest in G0/G1 phase, but had no effect on CREB and ERK phosphorylation. dbcAMP also induced ATP generation, but not autophagy or cell cycle arrest. These results suggest that the increased autophagy, ATP generation and cell cycle arrest caused by mTOR inhibition promotes the dbcAMP-induced differentiation of NG108-15 cells.
Dr. Chung-Der Hsiao Zebrafish skin is composed of enveloping and basal layers which form a first-line defense system against pathogens. Zebrafish epidermis contains ionocytes and mucous cells that aid secretion of acid/ions or mucous through skin. The killer/testing line binary system established in the current study demonstrates a nitroreductase/metrodinazole system that can be utilized to conditionally perform skin ablation in a real-time manner, and provides a valuable tool to visualize and quantify the anti-apoptotic potential of interesting target genes in vivo. The current work identifies a potential use for transgenic zebrafish as a high-throughput platform to validate potential apoptosis modulators in vivo.
Dr. Shu-Rung Lin The liver architecture plays an important role in maintaining hemodynamic balance, but the mechanisms that underlie this role are not fully understood. Hepsin, a type II transmembrane serine protease, is predominantly expressed in the liver, but has no known physiological functions. Here, we report that hemodynamic balance in the liver is regulated through hepsin. Deletion of hepsin (hepsin−/−) in mice resulted in enlarged hepatocytes and narrowed liver sinusoids. Using fluorescent microbeads and antihepsin treatment, we demonstrated that metastatic cancer cells preferentially colonized the hepsin−/− mouse liver as a result of the retention of tumor cells because of narrower sinusoids. The enlarged hepatocytes expressed increased levels of connexin, which resulted from defective prohepatocyte growth factor (pro-HGF) processing and decreased c-Met phosphorylation in the livers of hepsin−/− mice. Treatment of hepsin−/− mice with recombinant HGF rescued these phenotypes, and treatment of wild-type mice with an HGF antagonist recapitulated the phenotypes observed in hepsin−/− mice. Conclusion: Our findings show that the maintenance of hepatic structural homeostasis occurs through HGF/c-Met/connexin signaling by hepsin, and hepsin-mediated changes in liver architecture significantly enhance tumor metastasis to the liver.
Dr. Liang-Yi Wu Insulin and (−)-epigallocatechin gallate (EGCG) are reported to regulate obesity and fat accumulation, respectively. This study investigated the pathways involved in EGCG modulation of insulin-stimulated glucose uptake in 3T3-L1 and C3H10T1/2 adipocytes. EGCG inhibited insulin stimulation of adipocyte glucose uptake in a dose- and time-dependent manner. The concentration of EGCG that decreased insulin-stimulated glucose uptake by 50-60 % was approximately 5-10 µM for a period of 2 h. At 10 µM, EGCG and gallic acid were more effective than (−)-epicatechin, (−)-epigallocatechin, and (−)-epicatechin 3-gallate. We identified the EGCG receptor [also known as the 67-kDa laminin receptor (67LR)] in fat cells and extended the findings for this study to clarify whether EGCG-induced changes in insulin-stimulated glucose uptake in adipocytes could be mediated through the 67LR. Pretreatment of adipocytes with a 67LR antibody, but not normal rabbit immunoglobulin, prevented the effects of EGCG on insulin-increased glucose uptake. This suggests that the 67LR mediates the effect of EGCG on insulin-stimulated glucose uptake in adipocytes. Moreover, pretreatment with an AMP-activated protein kinase (AMPK) inhibitor, such as compound C, but not with a glutathione (GSH) activator, such as N-acetyl-L-cysteine (NAC), blocked the antiinsulin effect of EGCG on adipocyte glucose uptake. These data suggest that EGCG exerts its anti-insulin action on adipocyte glucose uptake via the AMPK, but not the GSH, pathway. The results of this study possibly support that EGCG mediates fat content.
Dr. Tzong-Yuan Wu Host protein synthesis is shut down in the lytic baculovirus expression vector system (BEVS). This also affects host proteins involved in routing secretory proteins through the endoplasmic reticulum (ER)-Golgi system. It has been demonstrated that a secretory alkaline phosphatase–EGFP fusion protein (SEFP) can act as a traceable and sensitive secretory reporter protein in BEVS. In this study, a chaperone, calreticulin (CALR), and the translation initiation factor eIF4E were co-expressed with SEFP using a bicistronic baculovirus expression vector. We observed that the intracellular distribution of SEFP in cells co-expressing CALR was different from co-expressing eIF4E. The increased green fluorescence emitted by cells co-expressing CALR had a good correlation with the abundance of intracellular SEFP protein and an unconventional ER expansion. Cells co-expressing eIF4E, on the other hand, showed an increase in extracellular SEAP activity compared to the control. Utilization of these baculovirus expression constructs containing either eIF4E or CALR offers a significant advantage for producing secreted proteins for various Biotechnological and therapeutic applications.
Dr. Chung-Yung Chen Bone marrow hematopoietic stem cells (HSCs) are crucial to maintain lifelong production of all blood cells. HSCs divide can differentiate into many kinds of blood cell types such as T cells, B cells and macrophages. HSCs originate during a differentiation period of active epigenetic remodeling. DNA methylation patterns are likely to be critical for their self-renewal, development and differentiation. Aberrant methylation of CpG islands is associated with transcriptional inactivation of genes involved in cell development, such as cell-cycle control, apoptosis signalling and DNA repair. Clinical trials of epigenetic therapies are now in progress, and epigenetic profiling using DNA methylation will provide guidance on optimization of the use of these therapies with conventional chemotherapy, as well as helping to identify patient populations who may particularly benefit from such approaches. To understand epigenetic patterns of differentiation, the PCR selective suppression hybridization strategy was designed to fetch all of genes that were changed their methylation statuses in CpG islands. After analysis of HSCs and CD8+ T cells using this approach, hundreds of methylated genes were recovered during comparison of HSCs and CD8+ T cells. Thus, this technology is able to detect methylation of CpG islands as high sensitivity and specificity and help to reveal the epigenetic CpG island evens during differentiation.
