Chi-Chang K. Shieh, M.D., Ph.D.
Joint-appointed Associate Investigator
Division of Infectious Diseases
EDUCATION-Ph.D., Immunology, Graduate Schools of Arts and Sciences, Harvard University, USA
-M.D., Medical School, College of Medicine, National Taiwan University, Taiwan
PROFESSIONAL EXPERIENCES- Joint-appointed Associate Investigator, Division of Clinical Research, National Health Research Institutes, Taiwan (2005-present)
- Associate Professor, Department Microbiology & Immunology and Pediatrics, National Cheng Kung University Medical College, Taiwan (2002-present)
- Director, Department of Pediatric Allergy and Immunolgy, National Cheng Kung University Hospital, Taiwan (2002- 2004)
- Assistant Professor, Department Microbiology & Immunology and Pediatrics, National Cheng Kung University Medical College, Taiwan (1998 -2002)
- Attending Physician, Department of Pediatric Allergy and Immunolgy, National Cheng Kung University Hospital, Taiwan (1997-present)
RESEARCH INTERESTSAs a clinician taking care of patients with immunological problems, Dr. Shieh is interested in finding the pathogenic mechanism underlying the diseases. Immunoregulation (e.g. ROS mediated modification of leukocyte function) and susceptibility for infectious diseases (e.g. tuberculosis and enterovirus) are among the main foci of research in his laboratory.
RESEARCH ACTIVITIES & ACCOMPLISHMENTSDuring my second year as an attending pediatrician in this University Hospital, I diagnosed the first patient with chronic granulomatous disease (CGD) in Tainan area. Using a flow cytometric method to measure leukocyte respiratory burst, I then helped to identify two more new patients with CGD in NTUH and VGH. I went on to identify novel mutations in the genes of NADPH oxidase in these patients. Detailed molecular characterization revealed that these mutations affect the molecular stability or the maturation process and lead to the phenotype of molecular deficiency in NADPH oxidase and failure to produce reactive oxygen intermediates (ROSs). The paper for this part of the research has been reviewed as "a valuable contribution to the field" and published in the journal of Biophysica Biochemica Acta (Molecular quality control machinery contributes to the leukocyte NADPH oxidase deficiency in chronic granulomatous disease. 2002). The study on these CGD mutations not only made it possible for prenatal diagnosis, but also opened the door for further investigation on the role of superoxide and other ROS in tissue inflammation.
As superoxide and ROS were recently recognized as regulatory mediators in inflammatory tissues, we employed our systems for measuring cell adhesion and ROS production to study the effects of ROS production and integrin mediated binding in leukocytes. Our data suggested that superoxide affect the integrin mediated binding of leukocytes to vascular adhesion molecule-1 (VCAM-1). This novel mechanism may contribute to the pathogenesis of asthma and allergic rhinitis (European Journal of Immunolgy, 2003).
By investigating the cross-talk between different integrins on integrins, we found that there is a previously unknown pathway with which LFA-1 integrin sends a signal through activation of NADPH oxidase and inhibits the activation of VLA-4 integrin (Blood, 2004).
- Liu YH, Chou HH, Jan RL, Liang CC, LIN HJ, Wang JY, Wu YC, Shieh CC (corresponding). Comparison of two specific allergen screening tests in different patient groups. Acta Paediatrica Taiwanica. 47:116-22, 2006.
- Wu YC, Huang YF, Lin CH, Shieh CC (corresponding). Detection of defective granulocyte function with flow cytometry in newborn infants. J Microbiol Immunol Infect. 38(1):17-24, 2005.
- Wang SM, Shieh CC, Liu CC. Successful treatment of Paecilomyces variotii splenic abscesses: a rare complication in a previously unrecognized chronic granulomatous disease child. Diagn Microbiol Infect Dis. 53:149-152, 2005.
- Wu YC, Haung YF, Lin CF, Shieh CC. Detection of Defective Granulocyte Function with Flow Cytometry in Newborn Infants. Journal of Microbiology Immunology and Infection. 38: 17-24, 2005.
- Chiou YY, Shieh CC, Cheng HL, Tang MJ. Intrinsic expression of Th2 cytokines in urothelium of congenital ureteropelvic junction obstruction. Kidney Internal. 67: 638-646, 2005.
- Chuang KP, Huang YF, Hsu YL, Liu HS, Chen HC, Shieh CC (corresponding). Ligation of lymphocyte function-associated antigen-1 on monocytes decreases very late antigen-4-mediated adhesion through a reactive oxygen species dependent pathway. Blood. 104: 4046-4053, 2004.
- Chuang KP, Tsai WS, Wang YJ, Shieh CC (corresponding). Superoxide Activates Very Late Antigen-4 on an eosinophil cell line and increases cellular binding to Vascular Cell Adhesion Molecule-1. Eur.J.Immunol. 33:645-655, 2003.