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專任教師

張永祺 助理教授

聯絡電話:02-23123456 轉 88892

E-mail: yungchiychang@ntu.edu.tw

個人資料

專長:

Host-pathogen interaction, Innate immunology

學歷:

Doctor of Philosophy
Department of Microbiology and Immunology, National Yang-Ming University, Taiwan

經歷:

Assistant project scientist (2012/8-2014/7)
Department of Pediatrics, University of California, San Diego, USA
Postdoctoral fellow (2007/12-2012/7)
Department of Pediatrics, University of California, San Diego, USA
Postdoctoral fellow (2006/7-2007/12)
Department of Microbiology and Immunology, National Yang-Ming University

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目前進行研究

In mammalian cells, sialic acid (Sia) is usually the terminal sugar residue on the oligosaccharide chains of cell-surface or serum glycoconjugates, where it functions in recognition and anti-recognition phenomena ranging from the regulation of complement activation to the control of cell–cell apposition. A key emerging concept in sialic acid (Sia) biology is the function of Siglecs (Sialic acid-binding immunoglobulin superfamily lectins) –the largest group of intrinsic Sia receptors mainly expressed by cells of the hematopoietic system. Siglecs are divided into two groups: an evolutionarily conserved sub-group (Siglecs-1, -2, -4 and -15) and a CD33/Siglec-3-related (CD33rSiglec) sub-group which appear to be rapidly evolving. A functional role for CD33rSiglecs in regulating innate immunity is suggested by the presence of tyrosine-based signaling motifs in their cytoplasmic tails, including a canonical ITIM (Immunoreceptor Tyrosine-based Inhibitory Motif (ITIM) motif. Negative regulation of immune functions by Siglecs with ITIMs has been reported in the realms of cell expansion, cytokine production, cellular activation and induction of apoptosis. Because of the abundance of sialic acid ligands on erythrocytes, plasma proteins and endothelial surfaces, Sia is proposed to act as self-associated molecular patterns (SAMPs), which are recognized by the inhibitory CD33rSiglec and serve to maintain a baseline non-activated state of innate immune cells, and help to counter-regulate inflammatory responses activated upon sensing of danger associated molecular patterns (DAMPs) or pathogen associated molecular patterns (PAMPs).

We seek to understand what happens when the glycobiological homeostasis of the mammalian host is perturbed by the intrinsic or exogenous factors introduced by infection or inflammation. Specifically, we want to examine innate and inflammatory functions of myeloid cells (neutrophils and macrophages) upon challenge by infectious microbes that either able to target host Siglecs or host sialoglycoproteins. A molecular genetic approach will be applied in the proposal to generate precise, live isogenic bacterial reagents that differ only by the gene of interest. Deploying this unique suite of tools, in which the host-pathogen equation is carefully manipulated in a controlled fashion from both sides, we will study infectious disease pathogenesis and innate immune responses in in vitro and in vivo models of myeloid cells.

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研究室成員

碩士班學生:李紹暳、曹靜怡、張鈞琪、劉昭賢、陳逸萱
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研究成果

1. Chang YC*, Nizet V (2014, Sep). The interplay between Siglecs and sialylated pathogens. Glycobiology, 24(9), 818-825.
2. Chang YC*, Olsen J, Louie A, Crocker PR, Varki A, Nizet V (2014, May). Role of macrophage sialoadhesin in host defense against the sialylated pathogen group B Streptococcus. Journal of Molecular Medicine, 10.1007/s00109-014-1157-y.
3. Padler-Karavani V, Hurtado-Ziola N, Chang YC*, Sonnenburg JL, Ronaghy A, Yu H, Verhagen A, Nizet V, Chen X, Varki N, Varki A, Angata T (2014, Mar). Rapid evolution of binding specificities and expression patterns of inhibitory CD33-related Siglecs in primates. FASEB Journal, 28(3), 1280-1293.
4. Chang YC*, Olson J, Beasley FC, Tung C, Zhang J, Crocker PR, Varki A, Nizet V (2014, Jan). Group B Streptococcus uses sialic acid mimicry to subvert host innate immune responses through engagement of inhibitory leukocyte receptor Siglec-E. PLoS Pathogen, 10(1), e1003846.
5. Angata T, Ishii T, Motegi T, Oka R, Taylor RE, Soto PC, Chang YC*, Secundino I, Gao CX, Ohtsubo K, Kitazume S, Nizet V, Varki A, Gemma A, Kida K, Taniguchi N (2013, Sep). Loss of Siglec-14 reduces the risk of chronic obstructive pulmonary disease exacerbation. Cellular and Molecular Life Sciences, 70(17), 3199-3210.
6. Huang ZM, Kang JK, Chen CY, Tseng TH, Chang CW, Chang YC*, Tai SK, Hsieh SL, Leu CM (2012, Jun). Decoy Receptor 3 suppresses TLR2-demiated B cell activation by targeting NK-kB. Journal of Immunology, 188(12), 5867-5876.
7. Chang YC*, Uchiyama S, Varki A, Nizet V (2012, Jan). Leukocyte inflammatory responses provoked by pneumococcal sialidase. MBio, 3(1), e00220-11.
8. Chang YC*, Wang Z, Flax LA, Xu D, Esko JD, Nizet V, Baron MJ (2011, Jun). Glycosaminoglycan binding facilitates entry of a bacterial pathogen into central nervous systems. PLoS Pathogen, 7(6), e1002082.
9. Tai SK, Yang MH, Chang SY, Chang YC*, Li WY, Tsai TL, Wang YF, Chu PY, Hsieh SL (2011, Apr). Persistent Kruppel-like factor 4 expression predicts progression and poor prognosis of head and neck squamous cell carcinoma. Cancer Science, 102(4), 895-902.
10. Carlin AF, Chang YC*, Areschoug T, Lindahl G, Hurtado-Ziola N, King CC, Varki A, Nizet V (2009, Aug). Protein-Mediated Engagement of Human Siglec-5 by the Pathogen Group B Streptococcus. Journal of Experimental Medicine, 206(8), 1691-1699.
11. Eguchi A, Meade BR, Chang YC*, Fredrickson CT, Willert K, Dowdy SF (2009, Jun). Efficient siRNA delivery into primary cells by a peptide transduction domain-dsRNA binding domain fusion protein. Nature Biotechnology, 27(6), 567-571.
12. Carlin AF, Uchiyama S, Chang YC*, Lewis AL, Nizet V, Varki A (2009, Apr). Molecular mimicry of host sialylated glycans allows a bacterial pathogen to engage neutrophil Siglec-9 and dampen the innate immune response. Blood, 113(14), 3333-3336.
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