聯絡資訊

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學歷

1989-1995 博士 美國威斯康辛大學麥迪遜分校 癌症生物研究所

1985-1987 碩士 陽明大學 生物化學研究所

1981-1985 學士 台灣大學 農業化學系

專長

人類疾病(如癌症及遺傳性疾病)之訊號傳導途徑及基因之調節

經歷

2009.08-2012.07 國立中正大學生命科學系 系主任

2008.02- 國立中正大學生命科學系 教授

2004.08-2008.01 中山醫學大學生物醫學科學 系主任

2003.12-2008.01 中山醫學大學生物醫學科學系 教授

1997.02-2003.11 中山醫學大學生物醫學科學系 副教授

2001.08-2004.07 中山醫學大學貴重儀器行政管理室 主任

1995.09-1997.01 美國北卡大學教堂山校區 博士後研究員

服務之委員會

財團法人中華民國證券櫃檯買賣中心外部審議委員,2012。

國立中正大學校務基金管理委員會委員,2012~2013。

Editorial Board of ISRN Genetics,2012。

國立嘉義大學生化科技系及微藥系教評委員 2011~2012。

國立中正大學人類受試倫理委員會主任委員、貴重儀器管理中心諮詢委員,2010-2012

高雄醫學大學生物醫學暨環境生物學系及生技系98學年度自我評鑑作業評鑑委員,2010

教育部99年度數位學習教材與課程認證審查委員(生命科學類) 2010

“The Journal of Neurological Science”期刊文章審查,2009

中山醫學大學系所評鑑審查小組委員, 2006-2007。

國科會計畫審查委員, 2005-2009。

教育部「大學校務評鑑規劃與實施計劃」評鑑委員 ─ 醫藥衛生類組, 2005。

“Oncogene” 期刊文章審查委員, 2003 & 2005。

“Neuroepidemiology” 期刊文章審查委員, 2004。

“中山醫誌” 期刊文章審查委員,2003-2007。

獎勵

國科會補助大專校院獎勵特殊優秀人才,2011~2012。

國立中正大學理學院”追求學術卓越獎勵” ,2010。

中山醫學大學教學優良教師, 2006。

台中市特殊優良教師, 2005。

Who's Who in Medicine and Healthcare, 5th ed., 2005。

國科會生物處研究獎勵甲種獎, 1999。

James M. Price Award, University of Wisconsin- Madison, Medical School, 1995.

Cremer Scholar of Department of Oncology, University of Wisconsin-Madison, Medical School, 1992-1995.

學術演講

2012 國立嘉義大學生化科技系、中國醫藥大學基礎醫學研究所、雲嘉南神經科季會。

2010 第一屆台灣線蟲年會

2009 國立清華大學生命科學院、中原大學生物科技學系

2008 長庚大學生命科學系

2007 高雄醫學大學、國立中正大學。

2006 國立成功大學。

2004 國立台灣師範大學、第二十屆生物夏令營

2004 中華民國人類遺傳學會暨中華民國遺傳學學會93年度秋季學術研討會、國立中興大學。

2003 東海大學。

2002 國立交通大學。

2001 第二屆臺灣生物技術暨分子診斷研討會。

2000 人類遺傳疾病研討會、第十屆亞洲小兒科醫學會、宜蘭羅東博愛醫院、國立中興大學。

研究計畫

2010-2013 國科會三年期研究計畫主持人

Study of RNA toxicity and underlying molecular mechanism of CAG trinucleotide repeats using C. elegans as a  model organism

2009-2010 國科會「充實研究設備提升生物科技研究能量-中正大學提昇生命科學研究能力計畫」主持人

2009-2011 國家型科技計畫共同主持人

奈米物質毒性評估平台的開發與建立

2008-2011 國科會三年期研究計畫共同主持人

Muscleblind 家族蛋白質的功能研究

2007-2010 國科會三年期研究計畫:

Study of the role of RNA-binding proteins in the pathogenic mechanism of trinucleotide repeats expansion diseases  using C. elegans as a model organism.

2006-2007 教育部顧問室95-96年度生物及醫學科技人才培育先導型計畫-醫衛分子檢驗領域。

2004-2007 國科會三年期研究計畫:

Functional analysis of trinucleotide repeats expansion in the 3’-UTR using C. elegans as a model system.

2001-2004 國科會三年期研究計畫:

Study of pathogenic mechanism of myotonic dystrophy using transgenic C. elegans as a model system.

1999-2001 國科會二年期研究計畫:

Genetic study of CTG trinucleotide expansion mutation in myotonic dystrophy locus.

1998-1999 國科會研究計畫:

Genetic analysis and study of pathogenic mechanism of myotonic dystrophy in Taiwan.

1997-1998 中山醫學院研究計畫:

Molecular study of myotonic dystrophy.

研究領域

我的研究興趣及主題是與人類疾病-如癌症和遺傳疾病-有關之訊號傳導途徑及基因表達之調節。細胞的增殖、分化、與死亡是生物體發育過程中三種非常重要之機制,疾病的發生常是因為調節這些機制之分子失去它們原有的功能所致。目前實驗室的研究主題以三聯核酸重複序列擴增造成之神經肌肉疾病,特別是強直型肌肉萎縮症(DM)為主。此外我們對於遺傳性肌強直症以及膽結石成因也有興趣。

三聯核酸重複序列神經肌肉疾病

利用細胞和線蟲作為模式生物我們探討轉譯區及非轉譯區內三聯核酸重複序列擴增對於體壁肌肉細胞及觸覺神經元功能之影響以及致病機制。其中,RNA結合蛋白質相關基因之選殖、生理功能、表達調節、下游目標基因確認、其表現代謝調控機轉及genetic modifiers的篩選是現階段研究重點。所利用技術包括基因選殖、基因轉殖、顯微注射、RNA干擾(RNAi)、免疫沉澱、螢光原位雜合(FISH)、細胞培養、啟動子活性調節分析等等。

先天性肌強直症

利用全基因掃瞄找出先天性肌強直症患者chloride基因變異(包括多型性及突變),配合核酸點突變技術以爪蟾卵母細胞作為模式系統進行電生理分析來調查基因型改變對chloride channel protein功能以及其對藥物反應之影響,未來並希望進一步探討chloride channel protein之轉譯後修飾對離子通道蛋白質功能之調節作用。利用技術包括DNA抽取、PCR、site-directed mutagenesis, cRNA synthesis等等。

膽結石成因

膽結石是一常見疾病,形成因素包括代謝以及遺傳。透過結石成份分析及家族資料檢體收集,希望找出結石形成相關基因變異。

研究興趣 | Research Interests

實驗室的研究主題以強直型肌肉萎縮症(DM)為主。強直型肌肉萎縮症是一種體染色體顯性遺傳之神經肌肉疾病,主要是因為DMPK基因3’端非轉譯區(3’-UTR)內一段CTG重複序列擴增所造成。疾病基因轉錄表達含擴增CUG序列的RNA,此RNA會改變CUG RNA結合蛋白質,包括muscleblind-like protein (MBNL) 及CUG-BP1,的活性進而影響多個基因的剪接或表現造成多系統的症狀。利用臨床病例收集及分子遺傳分析方法我們發現台灣地區DM盛行率甚低,符合罕見疾病之定義(<1/100,000)。在DM致病機轉研究方面,我們建立線蟲疾病動物模式,證明CUG序列RNA的生理效應隨序列長度增長及個體發育而愈來愈明顯並發現擴增的 CUG RNA可以將muscleblind隔離在核內形成聚集使其失去作用。以RNA干擾方法我們確認muscleblind表現量下降會造成與擴增的 CUG RNA類似的毒性效應。目前的研究著重在尋求能改善CUG RNA毒性的修飾基因,以及muscleblind作用機制的探討。

論文與著作

  1. Tsai Y.-C.*, Tseng C.-P., Hsiao K.-M., and Chen L.-Y. (1988). Production and characterization of D-aminoacylase from Alcaligenes denitrificans and taxonomic study of the strain. Appl. Environ. Microbio. 54: 984-989. (SCI)
  2. Yang Y.-B., Hsiao K.-M., Li H., Yano H., Tsugita A., and Tsai Y.-C.* (1992). Characterization of D-aminoacylase from Alcaligenes denitrificans DA181. Biosci. Biotech. Biochem. 56: 1392-1395. (SCI)
  3. Hsiao K.-M., Chou S.-Y., Shih S.-J., and Ferrell J. E. Jr.* (1994). Evidence that inactive p42 mitogen-activated protein kinase and inactive Rsk exist as a heterodimer in vivo. Proc. Natl. Acad. Sci. USA 91: 5480-5484. (SCI)
  4. Hsiao K.-M., McMahon S. L., and Farnham P. J.* (1994) Multiple DNA elements are required for the growth regulation of the mouse E2F1 promoter. Genes & Dev. 8: 1526-1537. (SCI)
  5. Verma A. K.*, Hsiao K.-M., Ahrens H., Suganuma M., Fujiki H., Matsufuji S., and Hayashi H. (1996) Superinduction of mouse epidermal ornithine decarboxylase activity by repeated 12-o-tetradecanoylphorbol-13-acetate treatments. Mol. Cell. Biochem. 155(2): 139-151. (SCI)
  6. van Ginkel P. R., Hsiao K.-M., Schjerven H., and Farnham P. J.* (1997) E2F-mediated growth regulation requires transcription factor cooperation. J. Biol. Chem. 272(29): 18367-18374. (SCI)
  7. Phelps D. E., Hsiao K.-M., Li Y., Hu N., Franklin D. S., Westphal E., Lee E. Y.-H. P., and Xiong Y*. (1998) Coupled transcriptional and translational control of cyclin-dependent kinase inhibitor p18INK4c expression during myogenesis. Mol. Cell. Biol. 18: 2334-2343. (DEP and KMH contributed equally to this paper) (SCI)
  8. Hsiao K.-M., Lin H.-M., Pan H., Li T.-C., Chen S.-S., Jou S.-B., Chiu Y.-L., Wu M.-F., Lin C.-C., and Li S.-Y.* (1999). Application of FTA® sample collection and DNA purification system on the determination of CTG trinucleotide repeat size by PCR-based Southern blotting. J. Clin. Lab. Anal. 13:188-193. (SCI)
  9. Hsieh M.* , Lin S.-J., Chen J.-F., Lin H.-M., Hsiao K.-M., Li S.-Y., Li C., and Tsai C.-J. (2000) Identification of the spinocerebellar ataxia type 7 mutation in Taiwan: application of PCR-based Southern blot. J. Neurol. 247: 623-629. (SCI)
  10. Jou S.-B., Lin H.-M., Pan H., Chiu Y.-L., Li S.-Y., and Hsiao K.-M.* (2001). Delineation of CTG repeats and clinical features in Taiwanese Myotonic Dystrophy family. Proc. Natl. Sci. Council, ROC. 25: 40-44.
  11. Pan H., Lin H.-M., Ku W.-Y., Li T.-C., Li S.-Y., Li C.-C., and Hsiao K.-M.* (2001). Haplotype analysis of the myotonic dystrophy type 1 (DM1) locus in Taiwan: implications for low prevalence and founder mutations of Taiwanese myotonic dystrophy type 1. Eu. J. Hum. Genet. 9: 638-641. (SCI)
  12. Pan H., Li Y.-Y., Li T.-C., Tsai W.-T., Li S.-Y., and Hsiao K.-M.* (2002) Increased (CTG/CAG)n lengths in the myotonic dystrophy type 1 and Machado-Joseph disease genes in idiopathic azoospermia patients. Hum. Reprod. 17: 1578-1583. (SCI)
  13. Hsiao M.-C., Kuo H.-C., Huang C.-C.*, Chiang S.-Y., and Hsiao K.-M. (2002) A posterior fossa cystic lesion in myotonic dystrophy: report of a case. J Acta Neurol. Taiwanica 11(3): 144-148. (SCI)
  14. Hsiao K.-M.* (2002) Reported relationship between increased CTG repeat lengths in myotonic dystrophy and azoospermia. Hum Reprod. 17(11):3004. (SCI)
  15. Kuo H.-C., Huang C.-C.*, Chu C.-C., Wai Y.-Y., Chiang S.-Y., and Hsiao K.-M. (2002) Brain magnetic resonance images and molecular genetic analysis in myotonic dystrophy. J Acta Neurol. Taiwanica 11(4): 187-193.
  16. Pan H.*, Liao S.-J., Lai W.-Y., Lu H.-C., and Hsiao K.-M. (2002) Overexpression but lack of mutation and methylation of p73 in hepatocellular carcinoma. Acta Oncol. 41: 550-555. (SCI)
  17. Pan H.*, Dung H.-N., Hsu H.-M., Hsiao K.-M., and Chen L.-Y. (2003) Cloning and developmental expression of p73 cDNA in zebrafish. Biochem Biophys Res Commun. 307(2):395-400. (SCI)
  18. Hsiao K.-M.*, Chen S.-S., Li S.-Y., Lin H.-M.,. Chiang S.-Y., Pan H., Huang C.-C., Kuo H.-C., Jou S.-B., Su C.-C., Ro L.-S., Liu C.-S., Lo M.-C., Chen C.-M., and Lin C.-C. (2003) Epidemiological and genetic studies of myotonic dystrophy type 1 in Taiwan. Neuroepidemiology 22(5):283-289. (SCI)
  19. Kuo H.-C., Huang C.-C.*, Chu C.-C., Chiang S.-Y., and Hsiao K.-M. (2003) Autosomal dominant myotonia congenita in a Taiwanese family and beneficial response to mexiletine. J Acta Neurol. Taiwanica 12(3): 130-135.
  20. Jou S.-B., Chang L.-I., Pan H., Chen P.-R., and Hsiao K.-M.* (2004) Novel CLCN-1 mutations in Taiwanese patients with myotonia congenita. Journal of Neurology 251: 666-670. (SCI)
  21. Li Y.-C., Cheng Y.-M., Hsieh L.-J., Ryder O.-A., Yang F., Liao S.-J., Hsiao K.-M., Tsai F.-J., Tsai C.-H., and Lin C.-C.* (2005) Karyotypic evolution of a novel cervid satellite DNA family isolated by microdissection from the Indian muntjac Y-chromosome. Chromosoma 114(1):28-38. (SCI)
  22. Kuo H.-C., Hsiao K.-M., Chen C.-J., Hsieh Y.-C., and Huang C.-C.* (2005) Brain magnetic resonance image changes in a family with congenital and classic myotonic dystrophy. Brain Dev. 27(4):291-296. (SCI)
  23. Kuo H.-C., Hsiao K.-M., Chang L.-I., You T.-H., Yeh T.-H., and Huang C.-C*. (2006) Novel mutations at carboxyl terminus of CIC-1 channel in myotonia congenita. Acta Neurol Scand. 113: 342–346. (SCI)
  24. Kuo H.-C., Huang C.-C., Chu C.-C., Wai Y.-Y., Hsiao K.-M., and Chu N.-S. (2006) Congenital myotonic dystrophy: variability in muscle involvement and histopathological process. J Acta Neurol. Taiwanica 15(1): 13-20.
  25. Lin M.-J., You T.-H., Pan H., and Hsiao K.-M.* (2006) Functional characterization of CLCN1 mutations in Taiwanese patients with myotonia congenita via heterologous expression. Biochem Biophys Res Commun. 351(4): 1043-1047. (SCI)
  26. Chen K.-Y., Pan H., Lin M.-J., Li Y.-Y., Wang L.-C., Wu Y.-C., and Hsiao K.-M.*. (2007) Length-dependent toxicity of untranslated CUG repeats on Caenorhabditis elegans. Biochem Biophys Res Commun. 352(3):774-779. (SCI)
  27. Chang T.-Y., Kuo H.-C., Hsiao K.-M., and Huang C.-C.* (2007) Phenotypic variability of autosomal dominant myotonia congenita in a Taiwanese family with muscle chloride channel (CLCN1) mutation. J Acta Neurol. Taiwanica 16(4): 214-220.
  28. Lin M.-J., Huang R.-Y., Pan H., and Hsiao K.-M.* (2008) Functional studies of the effect of NO donor on human CLCN1 polymorphism/ mutants expressed in Xenopus laevis oocytes. Biochem Biophys Res Commun. 365(4): 724-728. (SCI)
  29. Wang L.-C., Hung W.-T., Pan H*., Chen K.-Y., Wu Y.-C., Liu Y.-F., and Hsiao K.-M.* (2008) Growth-dependent effect of muscleblind knockdown on Caenorhabditis elegans. Biochem Biophys Res Commun. 366 (3): 705-709. (SCI)
  30. iu Y.-F., Liu H.-Y., Tu L.-C., Lin C.-W., Hsiao K.-M.*, and Pan H.* (2008) Zebrafish muscleblind genes: identification, structure features and expression. Comp. Biochem. Phys. B 151: 118-124.
  31. Chuang H.-N., Cheng H.-Y., Hsiao K.-M., Lin C.-W., Lin M.-L. and Pan H.*. (2010) The zebrafish homeobox gene irxl1 is required for brain and pharyngeal arch morphogenesis. Dev. Dyn. 239:639-650. (IF: 2.864; 2/19=10.5%)
  32. Hsiao K.-M., Huang R.-Y., Tang P.-H., and Lin M.-J.* (2010) Functional study of CLC-1 mutants expressed in Xenopus oocytes reveals that a C-terminal region Thr891-Ser892-Thr893 is responsible for the effects of protein kinase C activator. Cell Physiol Biochem 25:687-694. (IF: 3.585; 18/78=23%)
  33. Huang S.-M.,Yao C.-C., Cheng Y.-W., Chen L.-Y., Pan H*., Hsiao K.-M., Yang M.-D., Wu C.-W., and Lui W.-Y. (2010) Laparoscopic primary closure of common bile duct combined with percutaneous cholangiographic drainage for treating choledocholithiasis. Am. Surgeon. 76:517-521 (IF: 1.363; 84/188=45%)
  34. Huang S.-M. #,Yao C.-C. #, Pan H*, Hsiao K.-M. #, Lai T-J, and Huang S-D. (2010) The pathophysiologic significance of gallbladder volume changes in gallstone diseases. World Journal of Gastroenterology 16(34):4341-4347 (IF: 2.24; 33/72=49%, #equal contribution)
  35. Huang S.-M. #, Hsiao K.-M. #,Yao C.-C., Lai T.-J., Chen L.-Y., Pan H.*, Wu C.-W., and Lui W.-Y. (2011) Overcoming the difficulties in the laparoscopic management of contracted gallbladders with gallstones – possible role of fundus-down approach. Surgical Endoscopy 25(1): 284-291. (IF: 3.436, 15/188=7.97% in SURGERY, #equal contribution)
  36. Wang L.-C.#, Chen K.-Y.#, Pan H.#, Wu C.-C., Chen P.-H., Liao Y.-T., Li C., Huang M.-L., and Hsiao K.-M.* (2011) Muscleblind participates in RNA toxicity of expanded CAG and CUG repeats in Caenorhabditis elegans. Cell. Mol. Life Sci. 68:1255-1267. (IF: 7.047; 35/286=12.2% in BIOCHEMISTRY & MOLECULAR BIOLOGY)
  37. Hsu R.-J.#, Hsiao K.-M.#, Lin M.-J., Li C.-Y., Wang L.-C., Chen L.-K., and Pan H.* (2011) Long Tract of Untranslated CAG Repeats is Deleterious in Transgenic Mice. PLoS ONE. 6 (1): e16417.( IF:4.411; 12/86=13.9% in BIOLOGY) doi:10.1371/journal.pone.0016417 (January 21, 2011)
  38. Lee JD, Lee TH, Huang YC, Chang YJ, Chang CH, Hsu HL, Lin YH, Wu CY, Lee M, Huang YC, Ryu SJ, Hsiao K.-M.* (2011) ALOX5AP genetic variants and risk of atherothrombotic stroke in the Taiwanese population. J Clin Neurosci. Dec;18(12):1634-8. (IF:10165; 139/185=75% in CLINICAL NEUROLOGY)
  39. Lee JD, Lee TH, Kuo YW, Huang YC, Hsu HL, Lin YH, Wu CY, Huang YC, Lee M, Hsiao K.-M.* (2012) Polymorphisms at the LDLR Locus May Be Associated With Ischemic Cerebrovascular Disease Independent of Lipid Profile. Curr Neurovasc Res. Aug. (IF:3.047; 55/185=29.7% in CLINICAL NEUROLOGY)
  40. Yu JK#, Pan H#, Huang SM*, Huang NL, Yao CC, Hsiao K.-M., Wu CW (2012) Calcium content of different compositions gallstones and pathogenesis of calcium carbonate gallstones. Asian Journal of Surgery (in press).