生物標誌物研究室 高級助理研究員 
    劉佩芬 (Pei-Feng Liu)


    1. Ph.D. -Department of Life Science, National Tsing Hua University, Hsinchu, Taiwan (2007)
    2. M.S. -Department of Life Science, National Tsing Hua University, Hsinchu, Taiwan. (2001)
    3. B.S. -Department of Biology, Kaohsiung Medical University, Kaohsiung, Taiwan. (1999)

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    1. Senior Assistant Research Fellow-Department of Medical Education and Research, Kaohsiung Veterans General Hospital (2016-present)
    2. Adjunct Assistant Professor- Department of Nursing, Shu-Zen Junior College of Medicine and Management (2017-present)
    3. Postdoctoral Fellow- Department of Medical Education and Research, Kaohsiung Veterans General Hospital (2013-2016)
    4. Adjunct Assistant Professor- Department of Biotechnology, Fooyin University (2012-2017)
    5. Postdoctoral Fellow- College of Medicine, Kaohsiung Medical University (2011-2012)
    6. Visiting Scientist-Sanford-Burnham Medical Research Institute, La Jolla, CA, USA (2011)
    7. Postdoctoral Fellow- Division of Dermatology, University of California, San Diego, USA (2007-2011)
    1. Outstanding Paper Award, Kaohsiung Veterans General Hospital (2014, 2015)
    2. Graduate Student Grade Scholarship, National Tsing Hua University (2007)
    3. Graduate Student International Conference Attendance Scholarship, Ministry of Education (2006)
    4. Graduate Student International Conference Attendance Scholarship, NSC (2006)
    5. Graduate Student Poster Award, the 25th Botanical Society of Republic of China (2004)
    1. Developing diagnostic and prognostic biomarkers for various cancers
      The Cancer Genome Atlas (TCGA) database includes the most comprehensive genetic information of patients for most of cancer types. We have downloaded the database and implanted in SPSS software, which allow us to analyze expression level of any potential oncogenes or tumor suppressor genes. If the candidate genes appear significant difference in tumor development and prognosis, the candidate genes will be verified their function in several cancer cells using overexpression/knockdown experiments. The promising hits will be further examined the role in cell fucntion and tumor xenografted model. We will also obtain tissue microarray from either internal or commercial source to determine if the protein level of candidate genes is associated with tumor development and prognosis
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    2. Developing salivary and serum biomarkers for chronic inflammatory and aging-associated diseases
      Early detection of disease plays a crucial role in successful therapy. In most cases, the earlier the disease is diagnosed, the more likely it is to be successfully cured or well controlled. Managing a disease, especially in the early stage, may dramatically reduce the severity of its impact on the patient’s life, or prevent and/or delay subsequent complications. To overcome this challenge, medical researchers are devoted to finding molecular disease biomarkers that reveal a hidden lethal threat before the disease becomes complicated. These markers could be DNA, RNA, proteins, glucose, hormones or antibodies that act as indicators reflecting particular physiological states. In the past decade, scientists have demonstrated that abnormal molecules have been identified in blood, urine, saliva, and cerebrospinal fluid of patients and demonstrated to be effective biomarkers for diagnostic use. Saliva, a multi-constituent oral fluid, has high potential for the surveillance of general health and disease. Its unique properties include noninvasive accessibility, the presence of plentiful disease biomarkers, and can be easily collected by individuals with modest instruction and it dramatically reduces the discomfort of the tests. It is reported that most of the biomarkers present in blood and urine can also be detected in a sample of saliva. Changes of biomarker in saliva are believed to indicate the wellness of an individual. Furthermore, the concentration of some other disease biomarkers in saliva was found to exceed that in blood, illustrating a further advantage of using saliva for clinical diagnostics. Salivary biomarkers have been identified in many diseases such as oral cancer, periodontitis, dental carie, cardiovascular diseases and diabetes. In the study, salivary transcriptomic biomarkers, salivary protein biomarker (inflammatory cytokines) and salivary glucose from patients will be validated compared to serum biomarkers with by quantitative (q)PCR, enzyme linked immunosorbent assay (ELISA) and glucose colorimetric/fluorometric assay kit. Finally, the association of these salivary and serum biomarkers with the development of diseases especially for chronic inflammatory and aging-associated diseases will be evaluated. 
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    3. Developing vaccines and diagnostic biomarkers for infectious diseases
      Traditionally, the administration of a vaccine usually requires one or more needle injections performed by trained medical personnel.  The concept of a needle-free noninvasive technology may reduce medical costs by allowing personnel with limited medical training to administer the vaccine.  Moreover, the use of non-invasive routes for vaccine delivery such as nasal cavity with a large surface area, an excellent blood supply and a highly permeable epithelial membrane has the advantage of eliciting both local and systemic antibody response.  In addition, expression of antigenic proteins in bacterial culture may be the simplest and fastest strategy for generating large quantities of new vaccines.  Recombinant vaccines produced in bacteria, free of other viral and cellular components, can reduce pyogenic reaction and Guillain-Barre syndrome.  Furthermore, use of intact Escherichia coli (E. coli) particles as vaccine (E. coli-delivered vaccine) eliminates the time-consuming and deleterious requirement for the biochemical purification of antigens, the hazard of contemporary adjuvants, and the intrinsic problems associated with needle injections. Our research has been demonstrating that animals can be effectively immunized by intranasal vaccines produced in bacteria.  We have been generating many novel E. coli-vectored intranasal vaccines targeting periodontal infection and halitosis caused by Fusobacterium nucleatum (F. nucleatum), skin infection caused by Methicillin Resistant Staphylococcus aureus (MRSA) and Propionibacterium acnes (P. acnes).  Some of these studies have been published in international journals.  In the future, we will identify more potential diagnostic markers and preventive vaccines for infectious diseases.
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    4. Investigating interactions of bacterial virulence factors and host defenses
      Autophagy is an evolutionarily conserved process that catabolizes damaged proteins and organelles for sustaining ATP production during times of nutrient deprivation in the cells.  This evolutionarily conserved process plays an important role in many diseases, particularly in cancer development and infectious diseases.  Autophagy can function as an intracellular innate defense pathway in response to infection with a variety of bacteria and viruses. Autophagy serves as an antimicrobial defense mechanism that eliminates invading bacteria (a process called xenophagy) and plays a crucial role in host cell resistance to infection.  Numerous bacterial pathogens have developed the ability to invade host cells or to subvert host autophagy to establish a persistent infection. Although the precise mechanisms of autophagy on bacteria remain unclear, autophagosomes and phagosomes are involved in recruiting intracellular bacteria into lysosomes for bulk degradation.  In contrast, invading bacteria express virulence factors that attenuate host autophagic flux and allow escape from host attack: for example, IcsB of Shigella flexneri and the deubiquitinase SseL of Salmonella Typhimurium.  In our study, we observed elevated levels of IsaB, a virulence factor, in transmissible MRSA.  Elevated IsaB inhibits host autophagic flux and promotes MRSA inflammation and virulence. The study has been published in international journal.  Next, we will determine the detailed mechanisms of bacterial virulence factors on biofilm formation, autophagy regulation and inflammatory response in host cells.
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    (A.) Research Articles

    *: corresponding author
    1. PF Liu, CJ Hsu, WL Tsai, JS Cheng, JJ Chen, IF Huang, HH Tseng, HW Chang, CW Shu* (2017) “Ablation of ATG4B suppressed autophagy and activated AMPK for cell cycle arrest in cancer cells” Cellular Physiology and Biochemistry 44:728-740. (IF=5.104)
    2. PF Liu, Y Wang, CM Huang*, RG Ulrich, CW. Simmons, JS. VanderGheynst, and RL Gallo (2017) “Leaf-Encapsulated Vaccines: Agroinfiltration and Transient Expression of the Antigen Staphylococcal Endotoxin B in Radish Leaves” Journal of Immunology Research (In Press)
    3. Huang JS #, Yang CM # (co-equal first author), Wang JS, Liou HH, Hsieh IC, Li GC, Huang SJ, Shu CW, Fu TY, Lin YC, Ger LP, PF Liu * (2017) ” Caspase-3 Expression in Tumorigenesis and Prognosis of Buccal Mucosa Squamous Cell Carcinoma” Oncotarget 8(48):84237-84247. (IF=5.168)
    4. PF Liu, YC Hu, BH Kang, YK Tseng, PC Wu, CC Liang, YY Hou, TY Fu, HH Liou, IC Hsieh, LP Ger*, CW Shu*(2017) “Expression Levels of Cleaved Caspase-3 and Caspase-3 in Tumorigenesis and Prognosis of Oral Tongue Squamous Cell Carcinoma “PLoS One 12(7):e0180620.
    5. PF Liu, BH Kang, YM Wu, JH Sun, LM Yen, TY Fu, YC Lin, HH Liou, YS Lin, HC Sie, IC Hsieh, YK Tseng, CW Shu, YD Hsieh, LP Ger* (2017) “Vimentin is a Potential Prognostic Factor for Tongue Squamous Cell Carcinoma among Five Epithelial–mesenchymal Transition-related Proteins “PLoS One 12(6):e0178581.  
    6. PF Liu, Y Wang, YT Liu, CM Huang*. Vaccination with Killed but Metabolically Active E. coli Over-expressing Hemagglutinin Elicits Neutralizing Antibodies to H1N1 Swine Origin Influenza A Virus (2017). “Vaccination with Killed but Metabolically Active E. coli Over-expressing Hemagglutinin Elicits Neutralizing Antibodies to H1N1 Swine Origin Influenza A Virus” Journal of Nature and Science. 3(2). pii:e317.
    7. HH Tseng, YK Tseng, JJ You, BH Kang, TH Wang, CM Yang, HC Chen, HH Liou, PF Liu, LP Ger*, KW Tsai* (2017) “Next-generation Sequencing for microRNA Profiling: MicroRNA-21-3p Promotes Oral Cancer Metastasis” Anticancer Res. 37(3):1059-1066.
    8. TY Fu, CN Wu, HC Sie, JT Cheng, YS Lin, HH Liou, YK Tseng, CW Shu, KW Tsai, LM Yen, HW Tseng, CJ Tseng, LP Ger, PF Liu * (2016) “Subsite-specific Association of DEAD Box RNA Helicase DDX60 with the Development and Prognosis of Oral Squamous Cell Carcinoma” Oncotarget 7(51):85097-85108. (IF=5.168)
    9. CW Shu, HT Chang, CS Wu, CH Chen, S Wu, Chang HW, Kuo SY, Fu E, PF Liu* and Hsieh YD (2016)RelA-mediated BECN1 Expression is Required for Reactive Oxygen Species-Induced Autophagy in Oral Cancer Cells Exposed to Low-Power Laser Irradiation” PLoS One 11(9):e0160586.
    10. HW Chen, PF Liu, YT Liu, S Kuo, XQ Zhang, RT Schooley, H Rohde, RL Gallo, CM Huang *. (2016) “Nasal commensal Staphylococcus epidermidis counteracts influenza virus”. Scientific Reports 6:27870. (IF=5.228)
    11. CM Yang, TH Wang, HC Chen, SC Li, MC Lee, HH Liou, PF Liu, YK Tseng, YL Shiue, LP Ger* and KW Tsai* “Aberrant DNA hypermethylation-silenced SOX21-AS1 gene expression and its clinical importance in oral cancer “(2016) Clinical Epigenetics 8:129.
    12. YY Ho, JJ You, CM Yang, HW Pan, HC Chen, JH Lee, YS Lin, HH Liou, PF Liu, LP Ger* and KW Tsai*. (2016) “Aberrant DNA Hypomethylation of miR-196b Gene Contributes to Migration and Invasion of Oral Cancer” Oncology Letters 11: 4013-4021.
    13. PF Liu, JS Cheng, CL Sy, WC Huang, HC Yang, RL. Gallo, CM Huang and CW Shu* (2015) “IsaB Inhibits Autophagic Flux to Promote Host Transmission of Methicillin-Resistant Staphylococcus aureus” Journal of Investigative Dermatology 135(11):2714-22. (IF=7.216)
    14. WZ Liang#, PF Liu# (co-equal first author), E Fu, HS Chung, C-R Jan, CH Wu, CW Shu* and YD Hsieh* (2015) “Selective Cytotoxic Effects of Low-Power Laser Irradiation on Human Oral Cancer Cells” Lasers in  Surgery and Medicine 47(9):756-64.
    15. IF Huang¶, IC Lin¶, PF Liu, YC Liu, YD Hsieh, JJ Chen,CL Chen, HW Chang and CW Shu* (2015) “Lactobacillus Acidophilus Attenuates Salmonella-induced Intestinal inflammation via TGF-β signaling” BMC Microbiology 15(1):203.
    16. PF Liu, YD Hsieh, YC Lin, A Two, CW Shu* and CM Huang* (2015) Propionibacterium acnes in the Pathogenesis and Immunotherapy of Acne Vulgaris” Current Drug Metabolism 16(4):245-54.
    17. PF Liu, CM Leung, YH Chang, JS Cheng, JJ Chen, CJWeng, KW Tsai, CJ Hsu, YC Liu, PC Hsu, HW Pan and CW Shu* (2014). ATG4B Promotes Colorectal Cancer Growth Independent of Autophagic Flux. Autophagy 10(8):1454-65. (IF= 11.753)
    18. PF Liu, IF Huang, CW Shu* and CM Huang* (2013) “Halitosis Vaccines Targeting FomA, a Biofilm-bridging Protein in Fusobacteria nucleatumCurrent Molecular Medicine 13(8):1358-67. (IF= 4.197)
    19. WS Chen, TW Chen, TH Yang, LY Hu, HW Pan, CM Leung, SC Li, MR Ho, CW Shu, PF Liu, SY Yu, YT Tu, WC Lin, TT Wu* and KW Tsai* (2013). Co-modulated Behavior and Effects of Differentially Expressed miRNA in Colorectal Cancer. BMC Genomics 14 (Suppl 5):S12. (IF= 4.041)
    20. CW Shu*, PF Liu and CM Huang* (2012) ”High-Throughput Screening for Drug Discovery of Autophagy Modulators” Combinatorial Chemistry & High Throughput Screening 15(9):721-9  
    21. PF Liu, T Nakatsuji, W Zhu, RL Gallo and CM Huang* (2011) “Passive Immunoprotection Targeting a Secreted CAMP Factor of Propionibacterium acnes as a Novel Immunotherapeutic for Acne Vulgaris.”Vaccine 29(17), 3230-3238.
    22. PF Liu, WY Shi, WH Zhu, JW Smith, SL Hsieh, RL Gallo and CM Huang* (2010) “Vaccination Targeting Surface FomA of Fusobacterium nucleatum against Bacterial Co-Aggregation: Implication for Treatment of Periodontal Infection and Halitosis.” Vaccine 28(19), 3496-3505.
    23. CHs Chen, XQ Zhang, CW Lo, PF Liu, YT Liu, RL Gallo, MF Hsieh*, RT Schooley* and CM Huang* (2010) “The Essentiality of Alpha-2-Macroglobulin in Human Salivary Innate Immunity against New H1N1 Swine Origin Influenza A Virus.” Proteomics 10(12), 2396-2401. (IF=4.815)
    24. YK Wang, WC Chang, PF Liu, MK Hsiao, CT Lin, SM Lin and RL Pan* (2010).“Ovate Family Protein 1 as A Plant Ku70 Interacting Protein Involving in DNA Double-Strand Break Repair”. Plant Molecular Biology 74(4-5), 453-466.
    25. PF Liu, WH Zhu and CM Huang* (2009) “Vaccines and Photodynamic Therapies for Oral Microbial-Related Diseases.” Current Drug Metabolism 10(1), 90-94. (IF=4.350)
    26. PF Liu, SK Haake, RL. Gallo and CM Huang* (2009) “A Novel Vaccine Targeting Fusobacterium nucleatum against Abscesses and Halitosis.” Vaccine 27(10), 1589-1595.
    27. PF Liu, CW Lo, CH Chen, MF Hsien and CM Huang* (2009) “Use of Nanoparticles as Therapy for Methicillin-Resistant Staphylococcus aureus Infections.” Current Drug Metabolism 10 (8), 875-884. (IF=4.350)
    28. SH Hsu, YY Hsiao, PF Liu, SM Lin, YY Luo, and RL Pan* (2009) “Purification, Characterization, and Spectral Analyses of Histidine-Tagged Vacuolar H+-Pyrophosphatase Expressed in Yeast”. Botanical Studies 50, 291-301.
    29. JY Fang, PF Liu and CM Huang* (2008) “Decreasing Systemic Toxicity via Transdermal Delivery of Anticancer Drugs.” Current Drug Metabolism 9(7), 592-597. (IF=4.490)
    30. PF Liu, YK Wang, WC Chang, HY Chang and RL Pan* (2008) “Regulation of Arabidopsis thaliana Ku Genes at Different Developmental Stages under Heat Stress.” Biochimica et Biophysica Acta- Gene Regulatory Mechanisms 1779 (6-7), 402-407.
    31. CW Shu, FC Sun, JH Cho, CC Lin, PF Liu, PY Chen, MDT Chang, HW Fu and YK Lai* (2008) “GRP78 and Raf-1 Cooperatively Confer Resistance to Endoplasmic Reticulum Stress-Induced Apoptosis.” Journal of Cellular Physiology 215, 627-635. (IF=4.313)
    32. WC Chang#, YK Wang#, PF Liu, YF Tsai, LR Kong, CK Lin, CH Yang and RL Pan* (2008) “Regulation of Ku Gene Promoters in Arabidopsis by Hormones and Stress.” Functional Plant Biology 35, 265-280.
    33. PF Liu, WC Chang, YK Wang, HY Chang and RL Pan* (2008) “Signaling Pathways Mediating the Suppression of Arabidopsis thaliana Ku Gene Expression by Abscisic Acid.” Biochimica et Biophysica Acta-Gene Regulatory Mechanisms 1779(3), 164-174.
    34. PF Liu, WC Chang, YK Wang, SB Munisamy, SH Hsu, HY Chang, SH Wu and RL Pan* (2007)“Differential regulation of Ku gene expression in etiolated mung bean hypocotyls by auxins.” Biochimica et Biophysica Acta- Gene Regulatory Mechanisms 1769(7-8), 443-454.
    35. YY Hsiao, YJ Pan, SH Hsu, YT Huang, TH Liu, CH Lee, JH Li, PF Liu, WC Chang, YK Wang, LF Chien and RL Pan* (2007) “Identification of Essential Arg Residues Located in the Active Pocket of Mung Bean Vacuolar H+-Pyrophosphatase.” Biochimica et Biophysica Acta- Bioenergetics 1767, 965-973.
    36. SY Kuo, LF Chien, RC Van, KH Yan, PF Liu, WC Chang, JK Wang and RL Pan* (2005) “Purification and Subunit Determination of H+-Pyrophosphatase from Endoplasmic Reticulum-Enriched Vesicles of Mung Bean Seedlings.” Plant Science 169, 847-853.
    37. SY Kuo, LF Chien, YY Hsiao, RC Van, KH Yan, PF Liu, SJ Mao and RL Pan* (2005) “Proton Pumping Inorganic Pyrophosphatase of Endoplasmic Reticulum-Enriched Vesicles from Etiolated Mung Bean eedlings.” Journal of Plant Physiology 162, 129-138.
    38. KH Yan, PF Liu, HT Tzeng, WC Chang, WG Chou and RL Pan* (2004) “Characterization of DNA End-Binding Activities in Higher Plants.” Plant Physiology and Biochemistry 42, 617-622.

    (B) Conference Abstracts

    1. PF Liu, JS Cheng, CL Sy, WC Huang, HC Yang, RL Gallo, CM Huang, CW Shu* (2015). IsaB promotes host transmission of methicillin-resistant Staphylococcus aureus by inhibiting autophagy. The 7th International Symposium on Autophagy. HuangShan. China, P-54.
    2. PF Liu, CM Leung, YS Chang, JS Cheng, JJ Chen, CJ Weng, KW Tsai, CJ Hsu, YC Liu, PC Hsu, HW Pan, CW Shu * (2014). ATG4B promotes colorectal cancer growth independent of autophagic flux. Autophagy Keystone Symposium. TX, USA, P-3014.
    3. CW Shu*, PF Liu and JC Reed* (2013) High Throughput Screening Kinase Activators of Atg4B for Cancer Therapy. American Association Cancer Research, Washington D.C., USA, LB-128.
    4. CW Shu, A Pinkerton, MH, P Godoi, PF Liu, Charitha Madiraju, Dayong Zhai, Paul Diaz, Renata Sano and John C. Reed* (2011) “High-Throughput Screening for Small Molecule Inhibitors of Autophagins/Atg4 .”Autophagy Keystone Symposia, Whistler, Canada, P331.
    5. PF Liu, T Nakatsuji, RL Gallo and CM Huang* (2009) “Leaf-encapsulated Acne Vaccines: Agroinfiltration and Transient Expression of Propionibacterium acnes CAMP Virulence Factor as An Antigen in Radish Leaves.” 69th Annual Meeting of the Society for Investigative Dermatology, Montreal, Quebec, Canada, P124.
    6. PF Liu, WC Chang, YK Wang, MJ Juang and RL Pan*. (2006) “Involvement of Arabidopsis Ku in Heat Stress.” Plant & Animal Genomes XIV Conference, San Diego, CA, USA, P839.
    7. PF Liu, WC Chang, YK Wang and RL Pan*. (2006) “Regulation of Arabidopsis thaliana Ku Gene Expression by Abscisic Acid.” The American Society of Cell Biology, 46th Annual Meeting, San Diego, CA, USA, B17.
    8. WC Chang, PF Liu, YK Wang, MJ Juang and RL Pan*. (2006) “Using Fluorometric and Histochemical Methods to Detect the Gene Expression in Plant.” 1st European Chemistry Congress USING, Budapest, Hungary, Europe.