張二荃

張二荃，男，博士，畢業於美國加州大學聖地亞哥分校，北京生命科學研究所研究員。

基本介紹

  • 中文名：張二荃
  • 學位/學歷：博士
  • 職業：教師
  • 任職院校：北京生命科學研究所
個人經歷,學術成果,

個人經歷

教育經歷
2000–2004 美國加州大學聖地亞哥分校分子病理專業博士
1994–1997 復旦大學生物化學專業碩士
1990–1994 華東師範大學環境科學專業學士
工作經歷
2011- 北京生命科學研究所研究員
2006 – 2010 美國諾華製藥加州聖地亞哥研究院高級博士後研究員；兼美國加州大學聖地亞哥分校生物科學學院訪問學者
2004–2006 美國加州斯科瑞普斯研究所博士後

學術成果

研究概述
生物鐘對人類行為與生理有廣泛的調節作用。我們對生物鐘研究領域各個方面都感興趣，主要想回答三大問題：什麼是生物鐘？生物鐘如何進行調控？研究生物鐘有何重要意義？目前我們對以下幾個子課題特別感興趣：
  1. 對於哺乳動物的生物鐘而言，一個簡單的模型就是轉錄因子形成的延遲負反饋系統：轉錄正因子CLOCK和BMAL1結合，激活轉錄負因子PERIOD（包括PER1, PER2, PER3；簡稱PER）和CRYPTOCHROME（CRY1, CRY2；簡稱CRY）。PER與CRY表達積累到一定程度會反過來抑制CLOCK-BMAL1的活性，從而導致PER-CRY表達降低，形成每循環約24小時的負反饋環路。早期的小鼠行為篩選以及最近的全基因siRNA篩選都顯示有更多的生物鐘基因存在。我們準備運用系統生物學結合小鼠遺傳學方法研究新的生物鐘基因及其調控轉錄的分子機理，更深入理解生物鐘振盪器的相位，振幅，及周期。
  2. 視交叉上核（SCN）是負責生物鐘調控的主要器官，位於下丘腦前端。前期研究表明，SCN中存在一種特異性的分子機制暫時不明的耦合機理，促使其內的生物鐘異常強勁。我們準備運用合成生物學方法改造成纖維細胞，外加某種假設的耦合機理，使其變成SCN神經細胞。如獲得成功，我們就不僅解釋了耦合的分子機理，也會提供足夠的材料作生化分析，用以更深層次的解釋何以SCN區別於其它組織而作為生物鐘調控的中心。
  3. 我們對生物鐘如何調節進食行為很感興趣。當前的假說是，在大腦中存在一個獨立於SCN之外的"食物調控振盪器（FEO）"，用以整合生物鐘和食物需求的信息。我們將與清華大學宋森研究員的課題組合作，運用最新穎的光學遺傳學方法來尋找FEO。
  4. 生物鐘失調會導致代謝紊亂。為了充分發揮本研究員以前做高通量篩選（HTS）的特長已及套用NIBS擁有的最先進的HTS設備，我們會用此技術開創幾個探索性課題，用以了解生物鐘對酒精代謝和脂肪肝形成的影響。從這些細胞篩選方法得到的假說，我們會進一步運用小鼠遺傳學等體內方法來加以驗證。
Publications
  1. Zhang, E.E. and Kay, S.A. Clocks Not Winding Down: Unraveling Circadian Networks. (2010) Nature Reviews Molecular Cell Biology 11: 764-776 {Invited Review, 10-year Anniversary Series}
  2. Zhang, E.E.*, Liu, Y.*, Dentin, R., Pongsawakul, P.Y., Liu, A.C., Hirota, T., Nusinow, D.A., Sun, X., Landais, S., Kodama, Y., Brenner, D., Montminy, M. and Kay, S.A. Cryptochrome Mediates Circadian Regulation of cAMP Signaling and Hepatic Gluconeogenesis. (2010) Nature Medicine 16: 1152-1156 {Featured by Nature Medicine, "High glucose, no cry" (News and Views); Highlighted by Faculty of 1000, F1000 Factor = 8.0 (Must Read)}
  3. Hirota, T., Lee, J.W., Lewis, W.G., Zhang, E.E., Breton, G., Liu, X., Garcia, M., Peters, E.C., Etchegaray, J-P., Traver, D., Schultz, P.G. and Kay S.A. High-Throughput Chemical Screen Identifies a Novel Potent Modulator of Cellular Circadian Rhythms and Reveals CKI as a Clock Regulatory Kinase. (2010) PLoS Biology 8: e1000559
  4. Ko, C.H.*, Yamada, R.*, Welsh, D.K.*, Buhr, E.D., Liu, A.C., Zhang, E.E., Ralph, M.R., Kay, S.A., Forger, D. and Takahashi, J.S. Emergence of Noise-induced Oscillations in the Central Circadian Pacemaker. (2010) PLoS Biology 8: e1000513
  5. Zhang, E.E.*, Liu, A.C.*, Hirota, T.*, Miraglia, L.J., Welch, G., Pongsawakul, P.Y., Liu, X., Atwood, A., Huss, J.W.III., Janes, J., Su, A.I., Hogenesch, J.B., and Kay, S.A. A Genome-wide siRNA Screen for Modifiers of the Circadian Clock in Human Cells. (2009) Cell 139: 199-210 {Highlighted by Faculty of 1000, F1000 Factor = 10.0 (Exceptional); Highlighted by Cell, 2012 Collection on Circadian Rhythms}
  6. Hagihara, K.*, Zhang, E.E.*, Ke, Y-H.*, Liu, G., Liu, J-J., Rao, Y. and Feng, G-S. Shp2 acts downstream of SDF-1alpha/CXCR4 in guiding granule cell migration during cerebellar development. (2009) Developmental Biology 334: 276-284
  7. Lv, S.Q., Zhang, K.B., Zhang, E.E., Gao, F.Y., Yin, C.L., Huang, C.J., He, J.Q. and Yang, H. Antitumor Efficiency of the Cytosine Deaminase/5-Fluorocytosine Suicide Gene Therapy System on Malignant Gliomas: an In Vivo Study. (2009) Medical Science Monitor 15: BR 13-20
  8. Krajewska, M., Banares, S., Zhang, E.E., Huang, X., Scadeng, M., Jahla, U.S., Feng, G-S. and Krajewski, S. Development of Diabesity in Mice with Neuronal Deletion of Shp2 Tyrosine Phosphatase. (2008) American Journal of Pathology 172: 1312-1324
  9. Liu, A.C., Tran, H.G., Zhang, E.E., Priest, A., Welsh, D.K. and Kay, S.A. Redundant Function of REV-ERBα and β and Non-Essential Role for Bmal1 Cycling in Transcriptional Regulation of Intracellular Circadian Rhythms. (2008) PLoS Genetics 4: e1000023
  10. Pan, Y., Carbe, C. Powers, A., Zhang, E.E., Esko, J.D., Grobe, K., Feng, G-S. and Zhang, X. Bud Specific N-Sulfation of Heparan Sulfate Regulates Shp2-Dependent FGF Signaling during Lacrimal Gland Induction. (2008) Development 135: 301-310
  11. Ke, Y.*, Zhang, E.E.*, Hagihara, K., Wu, D., Pang, Y., Klein, R., Curran, T., Ranscht, B. and Feng, G-S. Deletion of Shp2 in the Brain Leads to Defective Proliferation and Differentiation in Neural Stem Cells and Early Postnatal Lethality. (2007) Molecular and Cellular Biology 27: 6706-6717
  12. Liu, A.C.*, Welsh, D.K.*, Ko, C.H., Tran, H.G., Zhang, E.E., Priest, A., Buhr, E.D., Singer, O., Meeker, K., Verma, I.M., Doyle, F.J.III., Takahashi, J.S. and Kay, S.A. Intercellular Coupling Confers Robustness Against Mutations in the SCN Circadian Clock Network. (2007) Cell 129: 605-616
  13. Nguyen, T.V., Ke, Y., Zhang, E.E. and Feng, G-S. Conditional deletion of Shp2 tyrosine phosphatase in thymocytes suppresses both pre-TCR and TCR signals. (2006) Journal of Immunology 177: 5990-5996
  14. Bard-Chapeau, E.A., Yuan, J., Dronin, N., Long, S., Zhang, E.E., Nguyen, T.V. and Feng, G-S. Concerted Functions of Gab1 and Shp2 in Liver Regeneration and Hepatoprotection. (2006) Molecular and Cellular Biology 26: 4664-4674
  15. Ke, Y., Lesperance, J., Zhang, E.E., Bard-Chapeau, E.A., Oshima, R.G., Muller, W.J. and Feng, G-S. Conditional deletion of Shp2 in the mammary gland leads to impaired lobulo-alveolar outgrowth and attenuated Stat5 activation. (2006) Journal of Biological Chemistry 281: 34374-34378
  16. pdong, p=
  17. Bard-Chapeau, E.A., Hevener, A.L., Long, S., Zhang, E.E., Oliesky, J. and Feng, G-S. Deletion of Gab1 in the Liver Leads to Enhanced Glucose Tolerance and Improved Hepatic Insulin Action. (2005) Nature Medicine 11: 567-571
  18. Zhang, E.E., Chapeau, E., Hagihara, K. and Feng, G-S. Neuronal Shp2 Tyrosine Phosphatase Controls Energy Balance and Metabolism. (2004) Proceedings of the National Academy of Sciences U.S.A. 110: 16064-16069
  19. Lai, L.A., Zhao, C., Zhang, E.E. and Feng, G-S. Chapter 14: The Shp-2 Tyrosine Phosphatase. Topics in Current Genetics: Protein Phosphatases by J. Arino and D. Alexander, (2004) Heidelberg: Springer-Verlag Publisher, ISBN: 3-540-20560-8, pp275-299 {book Chapter}
  20. Chen, Y., Wen, R., Yang, S., Schuman, J., Zhang, E.E., Yi, T., Feng, G-S. and Wang, D. Identification of Shp2 as a Stat5A Phosphatase. (2003) Journal of Biological Chemistry 278: 16520-16527
Patent Application:
  1. Feng, G-S. and Zhang, E.E. "Modulators of Shp2 tyrosine phosphatase and their use in the treatment of body weight disorders". USPTO Publication Document No. 20080058431; PCT Publication No. WO/2005/094314; Int'l Application No. PCT/US2005/010380; Priority Data 60/556,564 26-03-2004 US

熱門詞條

聯絡我們