錢家韻教授 >  研究方向 > Invited Lectures & 著作摘選>實驗室成員&畢業學生 >Collaborators
　
實驗室

錢嘉韻 教授
Iowa State University,  PhD 1981
 腦功能基因體研究室
護理館二樓214室
電話:2826-7102 或 分機:7102
          傳真:2820-0259
          mailto:acchang@ym.edu.tw           

　

　
研究方向

Research Interest:

1. Revelation of Neural Gene Functions using Transgenic and Knockout Mice Approach

           Functional characterization of novel neural genes and those previously uncovered in CNS areas implicated in cognition are currently 

    underinvestigation both in vitro and in vivo.  The candidate genes are 2 adrenoceptor subtype genes Adra2b and Adra 2c encoding a2B 

    and a 2C adrenoceptor respectively.  a2   adrenoceptor subtypes mediate the specific effect of norepinephrine via G protein-coupled signal 

    transduction pathways in selected areas in CNS.  Luzp is the  gene encoding a putative transcription factor LUZP predominantly expressed 

    in brain areas such as temporal cortex, hippocampus and cerebellum.

     Promoter-reporter transgenic mouse lines of both a2B and a 2C adrenoceptor have been established in which cis-elements-reporter 

constructs linking lacZ  were used to trace the temporal and spatial expression of specific receptor subtypes as directed by different domains 

of regulatory region of its gene.  These models  were employed to facilitate the study of receptor expression regulation. 

     We have also established 3 lines of knock-out mouse models in which the candidate genes; Adra2b, Adra 2c and Luzp, were each 

targeted disrupted and   a  reporter gene lacZ was in-frame inserted downstream to the regulatory region of respective genes.  The 

adrenoceptor subtype deficient mutants provide in  vivo models in which their respective expression atlas in brain may be established

 and their functional significance in emotion regulation (e.g., aggression and addictive behaviors) may be explored.  The LUZP-null mice

 are currently employed to delineate its role in neural tube closure in embryonic brain.  The selectivee

xpression of LUZP in hippocampus prompted the use of heterozygous Luzp-mutant to delineate its role in stress response by 

pharmacogenetic approach. Condition knockout mouse lines will be established employing the Tet-on system and specific

 promoter driven Cre-loxP recombinase system.  The mutant mice with definitive molecular lesion are excellent in vivo models in which 

the functional involvement of each candidate gene at the cellular, system, behavioral and cognitive levels may be assessed.

2. Immortalization and Characterization of Neural Cell Lines

           The myelin deficient (msd) rat is a model system for human demyelinating diseases.

     The mutant is characterized by defective oligodendrocytes , the central myelin synthesizing glia.  We have established and characterized 

    a clonal oligodendrocyte  line CBII.  Further characterization in terms of its functional competence; the capacity to make myelin both in vitro 

    and in vivo systems are  under pursue.  In  addition, we have established a murine neuronal cell line derived from embryonic (E13) 

    mesencephalon and used it as an in vitro model  system for mesolimbic dopaminergic neurons. We are in the process of characterizing its 

    apoptotic response to addictive drugs such that neural protective strategies may be devised.


　
Invited Lectures & 著作摘選
Invited Lectures  

 1. Molecular Cloning and Characterization of  2 Adrenoceptor Subtype Genes Sino-Japan Symposium on Neuroscience ,Jan 27-29, 1992,Taipei, 

     Taiwan, ROC

 2. Development of Embryonic Purkinje Cells Transplanted to Cerebellum of pcd Mutant Mice   Symposium and Workshop on Neurotransplantation ,

    June 27-28, 1992, Taipei, Taiwan, ROC

 3. Establishment and Characterization of a Clonal Oligodendrocyte Cell Line Derived from Rat Cerebellum.   Symposium and Workshop on Brain

    Cell Physiology, Oct. 17-22, 1992, Taipei, Taiwan, ROC

 4. Molecular Approaches to Nervous System Functions Second Annual Meeting of the Society for Basic Neuroscience, Nov. 28, 1993, Taipei, 

     Taiwan, ROC

 5. in vitro and in vivo Approaches to Study the Expression of a2 Adrenoceptor Subtype Genes Second Symposium on Frontiers in Neuroscience,

     July 5, 1995, Taipei, Taiwan, ROC

 6. PCR Applications for Neuroscientists 16th Conference of the Hong-Kong Society of Neruoscience, Dec. 14-15, 1995  , The University of Hong-Kong, 

     Hong Kong

 7. Approaches to Study the Expression of a2 Adrenoceptor Subtype Genes 16th Conference of the Hong-Kong Society of Neruoscience, Dec. 14-15, 1995,

     The University of Hong-Kong, Hong Kong

   8. Tracing the Expression of a2 Adrenoceptor in Transgenic Mice

        Symposium on Neuroscience, Section on ”Molecular Approaches to Neuroscience” March 8-10, 1997, NHRI, Taipei, Taiwan, ROC

    9. Spatial and Temporal Expression of a 2C 2 Adrenoceptor

        The 2nd Across the Taiwan Strait Symposium on Cell Biology ,Section on ”Molecular Developmental Biology”, Jan 26-28, 1999, NHRI, Taipei, Taiwan,

        ROC

  10. Molecular Characterization of a2 Adrenoceptor Subtype Genes University of Tokyo, Graduate Institut of Medicine, April 25, 2001, Tokyo, Japan

  11. Unraveling Neural Genes in Brain Areas Implicated in Cognition Symposium on ”Human Brain Project: Genomics, Functions and Diseases”, Oct. 18-20,

        2001, National Yang-Ming Univeristy, Taipei , Taiwan , ROC

  12. Establishment of Mutant Mouse Models to Study the Expression and Functions of Neural Genes ”Frontiers in Neuroscience 2001” Center for 

        Neuroscience, National Sun Yat-sen Univeristy.  Dec 21, 2001, Tainan, Taiwan

  13. Exploring the Function of Neural Genes in Mutant Mice Symposium on ”New Vistas for the Plasticity of Brain”, National Yang-Ming University Feb. 

       21-22, 2004, National Yang-Ming Univeristy, Taipei, Taiwan, ROC

  14. Norepinephrine Modulation of Emoitonal Memory: Lessons from Adra2b- and Adra 2c -Null Mice  The First TMU Neuroscience Synposium, Sept. 

       17-18, 2004, Taipei Medical University, Taipei, Taiwan

  15. Exploring the Role of Norepinephrine in Emotion as Defined by a2 Adrenoceptor The 20th Joint Conference of Biomedical Sciences, March 26-27, 

        2005, National Defense Medical Center , Taipei , Taiwan

  16. Modulation of Hippocampus Plasticity by Norpinephrine Unveiled in a 2C -Null Mice The Second NHRI Conference on Neuroscience, Sept. 29-30, 

       2005, Chu-Nan, Taiwan

Publications

    1.Chien A, DB Edgar and JM Trela (1976)  DNA polymerase from the extreme thermophile Thermus aquaticus.   J Bact. 127(3): 1550-1557.

     First to Discover and Report the Purification and Characterization of DNA polymerase of Thermus aquaticus (Taq polymerase)--  

     Taq polymerase  is Key to the Sucessful Application of Polymerase Chain Reaction (PCR)

     2.Chang AC and HD Dellmann (1981)  Biosynthesis and axoplasmic transport of neurophysins in the hypothalamo-neurohypophsyial system of the grass frog Rana pipiens. in  ”Neurosecretion: Molecules, Cells, System” DF Farner & K Lederis (eds), Plenum Press, New York, pp. 473-474.

     3.Chang AC and HD Dellmann. (1981)  Light and electron microscopic observations in the hypothalamo- neurohypophysial system of the grass frog Rana pipiens 

        after microiontophoresis of vinblastine into the median eminence. in “Neurosecretion: Molecules, Cell, Systems” DF Farner & K Lederis (eds),

Plenum Press, New York , pp. 471-472.

     4.Chang AC and HD Dellmann. (1984) A fine structure study of the formation of temporary swellings

(Herring bodies) and reversible degeneration of neurosecretory axons following microiontophoretic ejection of vinblastine into the hypothalamo-neurohypophysial tract of the frog Rana pipiens.   Exp Brain Res 53: 357-369.

     5.Chang AC and HD Dellmann. (1984)  Biosynthesis and axoplasmic transport of neurophysins in the hypothalamo-neurohypophysial system of Rana pipiens.

  J Neurosci 4(7): 1840-1849.

     6.Chang AC, CJ Alyea, LC Triarhou, WC Low and B Ghetti. (1988)  Expression of the developmentally regulated polypeptide PEP-19 by Purkinje cells transplanted to the cerebellum of pcd mutant mice. Anat Rec 220(4): 20-21.

     7.Chang AC, LC Triarhou, CJ Alyea, WC Low and B Ghetti. (1988)  Reactive gliosis in the cerebellum of pcd mutant host does not prevent the survival and differentiation of transplanted Purkinje cells. J Neuropathol Exp Neurol 47(3): 384.

     8.Chang AC, LC Triarhou, CJ Alyea, WC Low and B Ghetti. (1989)  Developmental expression of polypeptide PEP -19 in cerebellar cell suspensions transplanted into the cerebellum of pcd mutant mice. Exp Brain Res 76(3): 639-645

     09.Ghetti B, LC Triarhou, CJ Alyea, WC Low and AC Chang. (1990)  Timing of neuronal replacement in cerebellar degenerative ataxia of Purkinje cell type. Prog  Brain Res 82: 197-202.

     10.Chang AC, TF Ho and NC Chang.  (1990)  In vitro amplification by polymerase chain reaction of a partial gene encoding the third subtype of ��2 adrenergic   

          receptor in human. Biochem Biophys Res Commun 172(2): 817-823.  

     11.Chang AC, YH Lin, RL chou, GY Liao and NC Chang, (1992) Characterization of a glial associated antigen GA-1 by monoclonal antibody. Neurosci Lett  

          140: 192-196.

     12.Chen WM, AC Chang, BJ Shie, YH Chang and NC Chang. (1992)  Molecular cloning and characterization of a mouse�n�� 2C 2 adrenoceptor subtype  

           gene. Biochim Biophys Acta 1171: 219-223.        

     13.Sun SH and AC Chang. (1992)  Effects of sodium butyrate on phospholipid metabolism in a clonal rat brain oligodendrocyte cell line CB-II.  J Chin

          Biochem  21(2): 51-60.

   14.Chang YH , NC Chang, WM Chen and AC Chang. (1993)  Molecular characterization of a murine homologue of �� 2C 4 adrenoceptor subtype gene.    

           Biochem Mol Biol Internatl 29(3): 467-474

    15.Chang AC and B Ghetti. (1993)  Embryonic cerebellar graft development during acute phase of gliosis in the cerebellum of pcd mutant mice.  Chinese J  

           Physiol 36(3): 141-149

    16. Chang NC , Jenkins NA, Gilbert DJ, Copeland NG, Chang YH, Chen, WM and Chang AC. (1994)  Assignment of two ��2 adrenoceptor subtype genes 

           to murine chromosomes. Neuroscience Lett 167: 105-108.

    17. Wu SC , Chang NC, Chang AC, Chen WK, Yang TS, Shem PC and Lee KH. (1995)  Establishment of the technique of mouse embryo pronucleus  

           microinjection. J Chinese Soc Animal Sci 24(2): 181-189.                                                        

     18.Chen WM, AC Chang, CM Wang, CC Lin and NC Chang. (1996)  Characterization of the regulatory region of murine 2C 2 gene.  Neurosci Lett 210: 33

          -36.

    19.Sun DS, AC Chang, NA Jenkins, DJGilbert, NG Copeland and NC Chang. (1996)  Identification, molecular characterization and chromosomal 

          localization of  the cDNA encoding a novel leucine zipper motif-containing protein.  Genomics 36: 54-62.

     20.Fan SS, Chang NC , Chang AC and Yin HS. (1997) Differential expression of the GABAA receptor �nsubunit in developing brain.  NeuroReport 8: 2399- 

                 2404.

     21.Chang NC, Hung SI, Hwa KY, Kato I, Chen JE, Liu CH and Chang AC. (2001) A macrophage protein Ym1 transiently expressed during inflammation is 

          a novel mammalian lectin. J Biol Chem 276: 17497-17506

     22.Sun YJ, Chang , NC , Hung SI, Chang AC, Chou CC and Hsiao CD. The crystal structure of a novel mammalian lectin, Ym1 suggests a 

          saccharide binding site. J. Biol Chem 276: 17507-17514 (2001)

     23.Lee MWY, Chang AC, Sun DS, Hsu CY and Chang NC. Restricted expression of LUZP in neural lineage cells: a study in embryonic stem cells. 

          J Biomed Sci. 8: 504-511 (2001)

    24.Hung SI, Chang AC, Kato I and Chang NC . Transient expression of Ym1, a heapin-binding lectin, during developmental hematopoiesis and

          inflammation.  J Leukoc Biol 72(1): 72-82 (2002)

     25.Wang GS, Chang NC , Wu SC and Chang AC. Regulated expression of a2B adrenoceptor during development. Dev Dynamics 225:142-152 (2002)

     26.Chen WK, Chang NC, Chang YH, Chang, KC, Wu SC , Yang TS, Wu SM and Chang AC.

     Characterization of the regulatory region of Adra 2c , the gene encoding the murine a 2C adrencoeptor subtype. J Biomed Sci. 11: 886-901 (2004)

　

Manuscript in Preparation:

 

       1.Chang AC, Wang GS, Lee KH and Chang NC. Construction of an expression atlas of a2B adrenoceptor in the CNS using Adra2b-KO/lacZ-KI mutant 

           model. 

        2.Chang AC, Huang CC, Chen SJ, Lin SH, Liang KC, Lee KH and Chang NC. 

    Correlation of the spatial expression of a 2C adrenoceptor and aggressive behaviors in Adra 2c -KO/lacZ-KI mutant mice.

       3.Chang AC, Kung YJ, Chen WR, Linag KC and Chang NC.

   Emotional Episode-Elicted Hippocampus Plasticity Unveiled in a 2C -Null Mice

      4.Lin SH, Liang KC, Chen LS, NC Chang and Chang AC. 

  Role of  norepinephrine in ventral striatum unveiled by altered response to cocaine in Adra 2c -KO mice.

    5.Chang NC , ÕHsu CY, Lee, M.W., Lai SH, Lee KH and Chang AC.

  LUZP is crucial for neural tube closure: functional implication in the choreography of neurulation.

     6.Chang AC, Chiu JJ, Cheng MH, Hsu CY, Chou YC and Chang NC.

 Expression regulation of LUZP in hippocampus under stress.  

    7.JW Chang and Chang AC.

Characterization of a dopaminergic cell line (DM) derived from murine mesencephalon.

 
　
實驗室成員&畢業學生

Lab Members (2000-與本校微免所 張南驥教授共同指導)

  Ph.D. students  

  Institute of Neuroscience

王桂馨   Baylor College of Medicine, USA   Post Doc.

許家宜   Ph.D. Candidate

林星宏   Ph.D. Candidate

 Institute of Microbiology and Immunololgy

孫德姍   慈濟大學   助理教授

李婉瑩   國科會 生物處

洪舜郁   中研院 基因體中心

陳文貴   服役中

　

   M.S. Students
   Institute of Neuroscience

黃正球  Ph.D. Program, Baylor College of Medicine

鄭梅馨  Ph.D. Program, 國防大學

龔雍任  服役中

周志任 

陳麗仙

陳煒溶

林蕙竹

王穎之

楊玉綉

朱政吉

Institute of Microbiology and Immunololgy

劉姿吟 Ph.D. Program, University of Tubergen , Germany

陳勢杰 理律師事務所 (Patent Law)

黃聖傑 中研院 國防役


　
Collaborators

　

張南驥教授             國立陽明大學微免所 

                   信望愛臍帶血基金會 執行長

梁庚辰教授             國立台灣大學 心理學系及研究所主任

                   神經科學及認知科學研究中心  

吳信志助理教授     國立台灣大學  畜產系

李坤雄研究員         台灣動物科技研究所

蘇東平教授         台北榮總精神部主任

                   國立陽明大學神經科學研究所兼任教授

周元華 醫師        台北榮總精神部

陳景宗教授         長庚大學基礎醫學研究所生理藥理科主任

 林慶波助理教授      國立陽明大學神經科學研究所