醫學研究科

[醫研科行政業務] [動物研究實驗室]

[心臟血管研究室] [神經結構與功能研究室] [流行病學研究室]

[細胞藥理學研究室] [基因工程研究室] [感染疾病與免疫學研究室] [癌症基因體研究室] 

實驗室主持人

華 瑜 教授 (Julie Y.H. Chan, Ph.D.)   

 專長     學歷      經歷     學術資歷      獲獎與榮譽      研究主軸

目前正在進行之研究工作      研究論文目錄      會議或研討會發表論文

專長：神經科學、訊息傳遞、心臟血管生理學、氧化壓力   　

學歷：

• 1979　國立師範大學生物系理學士
• 1980　美國印地安那州立大學生命科學研究所碩士
• 1989　美國華盛頓州立大學神經科學研究所博士
• 1990　美國華盛頓州立大學神經科學研究所博士後研究員

經歷：

• 1990-1996 台北榮總教學研究部副研究員
• 1990-1996 國立陽明大學生理學研究所兼任副教授
• 1990-1996 國立陽明大學神經科學研究所兼任副教授
• 1996-1998 台北榮總教學研究部研究員
• 1996-  國立陽明大學生理學研究所兼任教授
• 1996-  國立陽明大學神經科學研究所兼任教授
• 1998-  高雄榮總教學研究部研究員
• 2002-  國立中山大學生命科學系兼任教授
• 2006- 高雄榮總基礎醫學研究科 科主任

學術資歷  

1. 世界自主神經科學會理事
2. 華人腦研究協會副會長
3. 中國生理學會理事
4. 台灣藥理學會理事
5. 中華民國基礎神經科學學會理事
6. 美國神經科學學會會員
7. 中國生理學會 理事長 (2008.05.05~)

獲獎與榮譽:

• 1991 -   青年獎章獲獎人
• 1992 -   國科會優等研究成果獎勵
• 1993 -   國科會優等研究成果獎勵
• 1995 -   中華藥理學會優秀論文獎
• 1996 -   行政院退除役官兵輔導委員會研究發展成果特優獎
• 1998 - 2001  香港大學醫學院生理系博士論文校外委員
• 2000 - 2001  香港醫政署專題研究計畫審查委員
• 2000 - 2003  國際自主神經科學學會理事
• 2001 -   台灣藥理學會傑出研究獎獲獎人
• 2002 -   中華民國基礎神經科學學會王世濬院士傑出研究獎座
• 2003 - 2005  國科會生物處生理學門召集人
• 2003 -   行政院科技類傑出研究獎獲獎人
• 2004 - 2008  國科會《生物醫學期刊》副主編
• 2005 -   行政院退除役官兵輔導委員會研究發展成果特優獎
• 2004 - 2007  國科會傑出研究獎獲獎人

研究主軸:  

   結合分子細胞生物學研究技術與系統功能表徵，本研究室研究宗旨在探討中樞神經系統參與生理與病理狀況下，腦部各區域結構與功能運作之基礎與致病之原因。探討之主軸包括高血壓神經機轉、脊髓受傷細胞分子病變、腦幹死亡分子機制與氧化傷害對腦部結構與功能之影響。研究領域橫向涵蓋分子生物學、基因調控、訊息傳遞機制、神經解剖、神經生理、神經化學等學門，縱向則以細胞、組織到系統功能，進行多元化、跨領域之整合性研究。

目前正在進行之研究工作:  

1. 中樞神經系統位於延腦腹外側之rostral ventrolateral medulla (RVLM)，為腦部調節血壓重要神經核之一，本研究室研究成果發現此核神經元與誘導性一氧化氮合成 酶(nNOS or iNOS)產生之一氧化氮(nitric oxide, NO)，在生理狀況下經由動態平衡，參與中樞調控心臟血管調節；而iNOS其蛋白質表現減少與功能衰竭，為造成神 經性高血壓之重要原因之一。目前研究著重iNOS基因調節與蛋白質代謝ubiquitin-proteosome system之研究，以進一步瞭解iNOS在RVLM引起高血壓之分子機轉。
2. 細胞內粒線體除為個體能量主要來源外，也是細胞超氧陰離子(superoxide anion)製造之主要胞器，超氧陰離子產生過剩或鏟除此離子之歧化酶功能失調，均為細胞氧化壓力(oxidative stress)之主要原因，也是造成個體氧化傷害之根本。本研究室先前實驗證明RVLM氧化壓力，為造成高血壓之重要角色，目前正進一步探討粒線體功能失調與超氧陰離子分解滯礙，在氧化壓力造成高血壓之細胞與分子機制。
3. 脊髓受損後，受傷細胞經由細胞壞死(necrosis)與凋亡(apoptosis)引起功能喪失，如何保護已受傷之脊髓細胞，避免其持續惡化步入細胞凋亡，為本研究室另一研究方向。目前研究重點放在粒線體功能保護、抗發炎與神經滋養因子等分子，並建立脊髓受損動物模式，由基因調控到功能修復，探討各種因素之重要性，研發可能保護策略。
4. 敗血性休克引起多器官衰竭，目前仍為重症病患導致病危之原因之一，本研究室過去實驗成果證明，除周邊循環系統功能衰竭外，中樞調節心臟血管功能失調，尤其是 RVLM神經核區活性喪失，在敗血性休克惡化過程中，佔有舉足輕重地位，而NO與氧化傷害兩者在此現象上均有參與。目前研究以iNOS及超氧陰離子為著眼點，探討此兩物質之重要性，並以此為根據，研發可能改善敗血性休克之策略。

研究論文目錄: (2002-2008發表論文如下)  

1.      Kung LC, Chan SH, Wu KLH, Ou CC, Tai MH, Chan JYH. (2008) Mitochondrial Respiratory Enzyme Complexes in Rostral Ventrolateral Medulla as Cellular Targets of Nitric Oxide and Superoxide Interaction in the Antagonism of Antihypertensive Action of eNOS Transgene.    Mol Pharmacol . [Epub ahead of print]

2.      Chen CH, Liu K, Chan JYH. (2008) Anesthetic preconditioning confers acute cardioprotection via up-regulation of manganese superoxide dismutase and preservation of mitochondrial respiratory enzyme activity. Shock . 29(2):300-8.

3.      Chen CH, Chuang JH, Liu K, Chan JYH. (2008) Nitric oxide triggers delayed anesthetic preconditioning-induced cardiac protection via activation of nuclear factor-kappaB and upregulation of inducible nitric oxide synthase. Shock . 30(3):241-9.

4.      Chan J.Y.H., C.H.Y. Wu, C.Y. Tsai, H.L. Cheng, K.Y. Dai, S.H.H. Chan and A.Y.W. Chang (2007) Transcriptional upregulation of nitric oxide synthase II by nuclear factor-kB at rostral ventrolateral medulla in mevinphos intoxication model of brain stem death. Journal of Physiology, in press.
doi: 10.1113/jphysiol.2007.130872

5.      Chan S.H.H., L.L. Wang, H.L. Tseng and J.Y.H. Chan (2007) Upregulation of AT₁ receptor gene on activation of PKCb-NADPH Oxidase-ERK1/2-c-fos signaling cascade mediates long-term pressor effect of angiotensin II in rostral ventrolateral medulla. Journal of Hypertension, in press.

6.      Chan J.Y.H., H.L. Cheng, J.L.J. Chou, F.C.H. Li, K.Y. Dai, S.H.H. Chan and A.Y.W. Chang (2007) Heat shock protein 60 or 70 activates NOS I- and inhibits NOS II-associated signaling, and depresses mitochondrial apoptotic cascade during brain stem death. Journal of Biological Chemistry, 282:4585-4600.

7.      Chan J.Y.H., A.Y.W. Chang, L.L. Wang, C.C. Ou and S.H.H. Chan (2007) Protein Kinase C-Dependent Mitochondrial Translocation of Pro-apoptotic Protein Bax On Activation of Inducible Nitric Oxide Synthase in Rostral Ventrolateral Medulla Mediates Cardiovascular Depression During Experimental Endotoxemia. Molecular Pharmacology, 71:1129-1139.

8.      Sheh Y.L., C. Hsu, S.H.H. Chan and J.Y.H. Chan (2007) NADPH oxidase- and mitochondrion-derived superoxide at rostral ventrolateral medulla in endotoxin-induced cardiovascular depression. Free Radical Biology & Medicine, 42:1610-1624.

9.      Wu K.L.H., C. Hsu and J.Y.H. Chan. (2007) Impairment of the mitochondrial respiratory enzyme activity triggers sequential activation of apoptosis-inducing factor-dependent and caspase-dependent signaling pathways to induce apoptosis after spinal cord injury. Journal of Neurochemistry, in press.
doi:10.1111/j.1471-4159.2006.0445.x

10.  Tai M.H., M.T. Weng, W.C. Lo, J.Y.H. Chan, C.J. Lin, H.C. Lam and C.J Tseng (2007) Role of nitric oxide in a-MSH-induced hypotension in the nucleus tractus solitarii of the spontaneously hypertensive rats. Journal of Pharmacology and Experimental Therapeutics, 321:455-461.

11.  Liu, G.S., L.F. Liu, C.J. Lin, J.C. Tseng, M.J. Chuang, H.C. Lam, J.K. Lee, L.C. Yang, J.Y.H. Chan, S.L. Howng and M.H. Tai. (2006) Gene transfer of pro-opiomelanocortin prohormone suppressed the growth and metastasis of melanoma: involvement of a-MSH-mediated inhibition of NF-kB/COX-2 pathway. Molecular Pharmacology, 69:440-451.

12.  Chan, S.H.H., M.H. Tai, C.Y. Li and J.Y.H. Chan. (2006) Reduction in molecular synthesis or enzyme activity of superoxide dismutases and catalase contributes to oxidative stress and neurogenic hypertension in spontaneously hypertensive rats. Free Radical Biology and Medicine, 40:2028-2039.

13.  Chang, A.Y.W., J.Y.H. Chan, Jimmy L.J. Chou, Faith C.H. Li, Kuang-Yu Dai, and S.H.H. Chan. (2006) Heat shock protein 60 in rostral ventrolateral medulla reduces cardiovascular fatality during endotoxemia in the rat. Journal of Physiology, 574:547-564.

14.  Chan, J.Y.H., S.H.H. Chan, K.Y. Dai, H.L. Cheng, J.L.J. Chou, and A.Y.W. Chang. (2006) Cholinergic receptor-independent dysfunction of mitochondrial respiratory chain enzymes, reduced mitochondrial transmembrane potential and ATP depletion underlie necrotic cell death induced by the organophosphate poison mevinphos. Neuropharmacology, 51:1109-1119.

15.  Chan, J.Y.H., S.H.H. Chan, F.C.H. Li, H.L. Cheng and A.Y.W. Chang. (2005) Phasic cardiovascular responses to mevinphos are mediated through differential activation of cGMP/PKG cascade and peroxynitrite via nitric oxide generated in the rat rostral ventrolateral medulla by NOS I and II isoforms. Neuropharmacology, 48:161-172.

16.  Tai, M.H., L.L. Wang, K.L.H. Wu and J.Y.H. Chan. (2005) Increased superoxide anion in rostral ventrolateral medulla contributes to hypertension in spontaneously hypertensive rats via interactions with nitric oxide. Free Radical Biology and Medicine, 38:450-462.

17.  Yen, D.H.T., J.Y.H. Chan, C.I. Huang, C.H. Lee, S.H.H. Chan and A.Y.W. Chang. (2005) Coenzyme Q10 confers cardiovascular protection against acute mevinphos intoxication by ameliorating bioenergetic failure and hypoxia in the rostral ventrolateral medulla of the rat. Shock, 23:353-359.

18.  Wang, L.L., C.C. Ou and J.Y.H. Chan. (2005) Receptor-independent activation of GABAergic neurotransmission and receptor-dependent nontranscriptional activation of phosphorydylinositol-3-kinase/protein kinase Akt pathway in acute cardiovascular actions of dexamethasone at the nucleus tractus solitarii of the rat. Molecular Pharmacology, 67:489-498.

19.  Li, F.C.H., J.Y.H. Chan, S.H.H. Chan and A.Y.W. Chang. (2005) Heat shock protein 70 (HSP70), but not HSP90, in the rostral ventrolateral medulla confers neuroprotection against fatal endotoxemia via augmentation of nitric oxide synthase I (NOS I)/protein kinase G signaling pathway and inhibition of NOS II/peroxynitrite cascade. Molecular Pharmacology, 68:179-192.

20.  Chan, S.H.H., K.L.H. Wu, L.L. Wang and J.Y.H. Chan. (2005) Nitric oxide- and superoxide-dependent mitochondrial signaling in endotoxin-induced apoptosis in the rostral ventrolateral medulla of rats. Free Radical Biology and Medicine, 39:603-618.

21.  Chan, S.H.H., K.S. Hsu, C. C. Huang, L.L. Wang, C.C. Ou and J.Y.H. Chan. (2005) NADPH oxidase-derived superoxide anion mediates angiotensin II-induced pressor effect via activation of p38 mitogen-activated protein kinase in the rostral ventrolateral medulla. Circulation Research, 97:772-780.

22.  Chan, J.Y.H., A.Y.W. Chang and S.H.H. Chan. (2005) New insights on brain
stem death: From bedside to bench. Progress in Neurobiology, 77:396-425.

23.  Tai, M.-H., M. Hsiao, J.Y.H. Chan, W.-C. LO, F. S. Wang, G.S. Liu, S. L. Howng and C.J. Tseng. (2004) Gene Delivery of eNOS into NTS induces biphasic response in cardiovascular functions of hypertensive rats. American Journal of Hypertension, 17:63-70.

24.  Chan, J.Y.H., S.H.H. Chan and A.Y.W. Chang. (2004) Contribution of cGMP but not peroxynitrite to negative feedback regulation of penile erection elicited by nitric oxide in the hippocampal formation of the rat. Neuropharmacology, 46:126-132.

25.  Chan, S.H.H., K.F. Chang, C.C. Ou and J.Y.H. Chan. (2004) Nitric oxide regulates c-fos expression in nucleus tractus solitarii induced by baroreceptor activation via cGMP-dependent protein kinase and CREB phosphorylation. Molecular Pharmacology, 65:319-325.

26.  Chan, J.Y.H., S.H.H. Chan and A.Y.W. Chang. (2004) Differential contribution of NOS isoforms in the rostral ventrolateral medulla to cardiovascular responses associated with Mevinphos intoxication in the rat. Neuropharmacology, 48: 1184-1194.

27.  Yen, D.H.T., J.Y.H. Chan, H.P. Tseng, C.I. Huang, C.H. Lee, S.H.H. Chan and A.Y.W. Chang. (2004) Depression of mitochondrial respiratory enzyme activity in rostral ventrolateral medulla during acute Mevinphos intoxication in the rat. Shock, 21:358-363.

28.  Chan, J.Y.H., C.C. Ou, L.L. Wang and S.H.H. Chan. (2004) Heat shock protein 70 confers cardiovascular protection during endotoxemia via inhibition of nuclear factor-kB activation and inducible nitric oxide synthase expression in the rostral ventrolateral medulla. Circulation, 110:3560-3566.

29.  Chan, S.H.H., L.L. Wang, K.F. Chang, C.-C. Ou and J.Y.H. Chan. (2003) Altered temporal profile of heat shock factor 1 phosphorylation and heat shock protein 70 expression induced by heat shock in nucleus tractus solitarii of spontaneously hypertensive rats. Circulation, 107:339-345.

30.  Chan, S.H.H., L.L. Wang and J.Y.H. Chan. (2003) Differential engagement of glutamate and GABA receptors in cardiovascular actions of endogenous nNOS or iNOS at rostral ventrolateral medulla of rats. British Journal of Pharmacology, 138:584-593.

31.  Chan, J.Y.H., L.L. Wang, Y.M. Chao and S.H.H. Chan. (2003) Down-regulation of basal iNOS at rostral ventrolateral medulla is innate in SHR. Hypertension, 41:563-570.

32.  Chang, A.Y.W., J.Y.H. Chan and S.H.H. Chan. (2003) Differential distribution of nitric oxide synthase isoforms in rostral ventrolateral medulla of the rat. Journal of Biomedical Science, 10:285-291.

33.  Chuang, Y.-C., J.Y.H. Chan, A.Y.W. Chang, M. Sikorska, C.-W. Liou and S.H.H. Chan. (2003) Neuroprotective effects of coenzyme Q10 at rostral ventrolateral medulla against fatality during experimental endotoxemia in the rat. Shock, 19:427-432.

34.  Shih, C.D., L.C. Au and Chan, J.Y.H. (2003) Differential role of leptin receptors at the hypothalamic paraventricular nucleus in tonic regulation of food intake and cardiovascular functions. Journal of Biomedical Science, 10:367-378.

35.  Chan, J.Y.H., L.L. Wang, C.C. Ou and S.H.H. Chan. (2003) Downregulation of angiotensin subtype 1 receptor in rostral ventrolateral medulla during endotoxemia. Hypertension, 42:103-109.

36.  Wu, K.L.H., S.H.H. Chan, Y.M. Chao and J.Y.H. Chan. (2003) Expression of pro-inflammatory cytokine and caspase genes promotes neuronal apoptosis in pontine reticular formation after spinal cord injury. Neurobiology of Disease, 14:19-31.

37.  Chan S.H.H., K.F. Chang, C.C. Ou and J.Y.H. Chan. (2002) Up-regulation of glutamate receptors in nucleus tractus solitarii underlies potentiation of baroreceptor reflex by heat shock protein 70. Molecular Pharmacology, 61: 1097-1104.

38.  Chan, A.Y.W., C.M. Huang, F.J. Kao, J.Y.H. Chan and S.H.H. Chan. (2002) Involvement of nitric oxide generated by nNOS and iNOS at hippocampal formation in negative feedback regulation of penile erection in the rat. British Journal of Pharmacology, 136: 1-8.

39.  Chan, S.H.H., Y.M. Chao, C.J. Tseng and J.Y.H. Chan. (2002) Down-regulation of basal Fos expression at nucleus tractus solitarii underlies restoration of baroreflex response after antihypertensive treatment in spontaneously hypertensive rats. Neuroscience, 112: 113-120.

40.  Chuang, Y.C., J.L. Tsai, A.Y.W. Chang, J.Y.H. Chan, C.W. Liou and S.H.H. Chan. (2002) Dysfunction of mitochondrial respiratory chain in rostral ventrolateral medulla during experimental endotoxemia in the rat. Journal of Biomedical Science, 9: 542-548.

41.  Chan, J.Y.H., L.L. Wang, H.-Y. Lee and S.H.H. Chan. (2002) Augmented up-regulation by c-fos of angiotensin subtype 1 receptor in NTS of SHR. Hypertension, 40: 335-341.

42.  Chan, S.H.H., L.L. Wang, C.-C. Ou and J.Y.H. Chan. (2002) Contribution of peroxynitrite to fatal cardiovascular depression induced by overproduction of nitric oxide in rostral ventrolateral medulla of the rat. Neuropharmacology, 43:889-898.

43.  Lo, W.C., J.Y.H. Chan, C.S. Tung and C.J. Tseng. (2002) Carbon monoxide and metabotropic glutamate receptors in rat nucleus tractus solitarii: participation in cardiovascular effect. European Journal of Pharmacology, 454:39-45.

會議或研討會發表論文：  

由1980年開始至今發表180篇論文(目錄未附)。