謝政哲 博士, Jeng-Jer Shieh Ph.D.

電子郵件: shiehjj@dragon.nchu.edu.tw; shiehjj@vghtc.gov.tw

實驗室位置: 台中榮民總醫院 研究大樓116A (office),201室(Lab.)

實驗室電話: (04)23592525 分機4061

辦公室電話: (04)23592525 分機4052

傳真: (04)23592705

簡要經歷

教授 國立中興大學生物醫學研究所 2016-

副教授 國立中興大學生物醫學研究所 2012 - 2016

助理教授 國立中興大學生物醫學研究所 2009 -2012

助理教授 國立中興大學醫學科技研究所 2006 - 2009

特約研究員 台中榮民總醫院研究部 2016-

特約副研究員 台中榮民總醫院研究部 2006- 2016

助理教授 私立長榮大學醫學研究所 2003 - 2006

兼任研究員 彰化基督教醫院教研部 2003 - 2006

博士後研究 美國國家衛生研究院(NIH, USA) 2000 – 2003

博士後研究 中央研究院生物農業科學研究所籌備處 1998-2000

博士後研究 台北榮民總醫院小兒部 1997-1998

博士 國立陽明大學微生物及免疫研究所 1991-1997


研究方向

類鐸受體7(Toll-like receptor 7)活化劑Imiquimod誘發腫瘤細胞進行細胞凋亡(apoptosis)與細胞自噬(autophagy)之相關性及分子機制。

類鐸受體7活化與能量代謝調控基因表現差異之相關性及調控機制。

老藥新用於癌症治療方法之研究與開發。

乾癬致病機制, 動物模式之建立及藥物篩選。


研究主題

本實驗室研究主題可分為兩大部份:第一部份主要是以細胞分子生物學的角度探討葡萄糖-6-磷酸酶(glucose-6-phosphatase)和其相關蛋白之結構及功能上的關係及其表現與先天免疫活化之關係。第二部份主要是以皮膚癌細胞為生物模式,探討類鐸受體(Toll-like receptor)免疫製劑之抑癌機制及開發新穎之標的基因治療方法。其主要研究重點如下:

(一)發現V型葡萄糖六 磷酸轉移蛋白(vG6PT)的蛋白質較G6PT不穩定,這是因exon 7在選擇性剪接時加入vG6PT mRNA所造成。在小鼠的組織中具有和人類幾乎相同的G6PT mRNA剪接模式。而誘發此G6PT的選擇性剪接可能與在肌肉細胞株的分化過程有關。而類鐸受體之活化可調控葡萄糖-6-磷酸酶(glucose-6-phosphatase)和其相關蛋白在不同組織之表現變化。目前研究重點為G6PT的選擇性剪接在肌肉細胞株中的分子機制及類鐸受體調控葡萄糖-6-磷酸酶(glucose-6-phosphatase)和其相關蛋白之分子機制。發現G6Pase新突變點M121V,證明其與肝醣貯積症第1型之臨床症狀相關性 (Gene, 2012)

(二) 表現Mcl-1S (Mcl-1 之另類剪接異構蛋白)可誘發基底細胞癌細胞凋亡,因此運用Antisense Morpholino oligonucleotides 來促使基底細胞癌細胞株朝向進行Mcl-1S的選擇性剪接,增加促凋亡Mcl-1S表現且同時減少抗凋亡Mcl-1L表現。如此,在基底細胞癌中改變Mcl-1S的剪接型態能誘使細胞產生凋亡,為一可行之基因治療方法(Journal of Investigative Dermatology, 2009)。目前研究重點為Mcl-1S蛋白結構及功能的相關性。

J Invest Dermatol. 2009; 129(10):2497-506

(三) 發現類鐸受體7活化劑Imiquimod(IMQ)可以直接誘發不同癌細胞細胞自噬(autophagy)及細胞凋亡(apoptosis),自噬性死亡及細胞凋亡是誘發基底細胞癌細胞死亡之主要途徑 (British Journal of Dermatology, 2010)。IMQ可透過活化AMPK之路徑來達成轉錄抑制降低Mcl-1的表現, 進而誘導細胞凋亡而非細胞自噬 (Journal of Dermatological Science, 2012, 2015) 。 數種腫瘤細胞株在IMQ的處理下可誘發HIF-1α表現並使代謝趨向有氧醣解(aerobic glycolysis)途徑,而抑制有氧醣解及HIF-1α則可加強imiquimod毒殺腫瘤能力(Oncotarget, 2014)。 IMQ可在人體皮膚癌細胞中誘導ROS產生並活化ATM及ATR進而造成p53依賴的細胞凋亡(Journal of Dermatological Science, 2016)。IMQ所誘導的ROS亦可刺激ER stress,活化PKR,進而誘導細胞自噬的發生(Journal of Dermatological Science, 2017 )。IMQ所誘導的ROS亦可造成粒線體損傷及斷裂,進而被自噬體吞噬(Journal of Dermatological Science, 2020) 。證明IMQ為一種ICD(immunogenic cell death,免疫性細胞死亡)促進劑,配合2-DG使用可增強癌細胞ICD,並於活體中誘發抗癌細胞專一免疫反應,抑制腫瘤生長,提高活體存活率(Journal of Investigative Dermatology, 2020) 。在癌細胞中,IMQ誘導ROS大量產生可損害溶酶體,降低溶酶體功能,產生溶酶體壓力。為了補償此點,溶酶體生成因子TFEB活化強化溶酶體生成來進行溶酶體調適,其結果聚積更多IMQ於新溶酶體中,進而降低IMQ的細胞毒性。在細胞和動物模式中干擾溶酶體調適,可協同增強IMQ毒殺癌細胞能力 (Journal of Investigative Dermatology, 2021) 。

Brit J Dermatol. 2010; 163(2): 310-20

(四)建立乾癬(Psoriasis)動物模式,並篩選目前臨床用藥對減緩或治癒乾癬的可能性與機制。建立以IMQ誘發乾癬之小鼠動物模式並發現傳統抗生素Azithromycin可在此模式中藉由抑制樹突細胞活化等成功降低乾癬之臨床症狀,抑制IL-17/IL-23作用軸線, 抑低Th17細胞族群( Journal of Dermatological Science, 2016)。發現在糖尿病病人族群中服用抗糖尿病用藥可降低罹患乾癬之風險(Journal of the American Academy of Dermatology, 2015) 。抑鬱症和失眠患者的乾癬及乾癬關節炎病人服用腫瘤壞死因子拮抗劑可有效降低抑鬱症和失眠症狀(Medicine, 2016)

J Dermatol Sci. 2016, 84(1): 59-70

(五) 在臨床統計資料、細胞學實驗及動物活體實驗證實糖尿病用藥AMPK活化劑metformin能藉由活化LKB1、AMPK之路徑,使p21及p27表現增加並使cyclin D1下降,進而使肝癌細胞進入細胞週期G1停滯而減緩肝癌細胞增生。證實糖尿病患者服用metformin能有效降低肝癌之罹患風險 (Gut, 2013) 。而AMPK抑制劑compound C可透過ROS造成DNA損傷,並透過活化ATM/Chk2/p53途徑在p53野生型細胞中誘發細胞凋亡,但在p53突變型細胞中誘發G2/M停滯(Toxicology and Applied Pharmacology, 2013) 。降血脂用藥simvastatin能活化AMPK及抑制STAT3/Skp2路徑分別促進p21基因表現及p27蛋白穩定,使肝癌細胞進入生長週期停滯,減緩肝癌細胞增生(Cell Death and Disease, 2017)。降血脂用藥atrovastatin能透過抑制IL6/STAT3/Telomerase路徑誘導肝癌細胞細胞老化(senescence)(Cell Death Discovery, 2020) 。

Cell Death and Disease. 2017, 8, e262

(六)發現皮膚角質細胞在Th2環境下, Heat shock protein可抑制TSLP表現進而抑制發炎症狀, 此現象可說明Heat shock protein在過敏性皮膚炎可能有療效(Pediatric Allergy and Immunology, 2016)。慢性鐵質過載在THP1巨噬細胞中會造成溶酶體pH值上升, 功能受損進而引起溶酶體生合成失衡, 最後導致THP1巨噬細胞抑菌能力下降, 此機制可以為嚴重地中海型貧血患者因慢性鐵質過載所受損之先天免疫功能提供另一面向之說明(Plos One, 2016)。慢性鐵質過載可驅使THP1巨噬細胞分化為M2-like細胞(Annals of Hematology, 2020) 。


教授科目

分子癌症學(合開)

基礎癌症醫學(合開)

分子細胞生物學(合開)

高等細胞生物學(合開)

生物醫學新知與應用(合開)

基因及幹細胞醫學科技特論 (一, 二)

生物技術在臨床醫學之應用

老化研究特論

細胞自噬特論

先天免疫學特論

專題討論

專題研究

文獻探討


學術著作

期刊論文:(*corresponding author)

Daniel J. Klionsky and 2299 others. Guidelines for the use and interpretation of assays for monitoring autophagy (4rd edition). Autophagy. 2021; 17(1): 1-382. (review; SCI, impact factor: 11.753, Ranking: 15/184 CELL BIOLOGY)

Chung MC, Lin CL, Wu MJ, Chen CH, Shieh JJ, Chung CJ, Li CY, Yu TM. Primary aldosteronism is associated with risk of urinary bladder stones in a nationwide cohort study. Sci Rep. 2021, 11(1):7684.

Chang SH, Wu CY, Chuang KC, Huang SW, Li ZY, Wang ST, Lai ZL, Chang CC, ChenYJ, Wong TW, Kao JK, Shieh JJ*. Imiquimod Accelerated Antitumor Response by Targeting Lysosome Adaptation in Skin Cancer Cells. Journal of Investigative Dermatology. 2021 Mar17:S0022-202X(21)01002-2. doi: 10.1016/j.jid.2021.01.034. (SCI, impact factor: 7.143, Ranking: 3/68 DERMATOLOGY). *Corresponding author.

Chuang KC, Chen FW, Tsai MH*, Shieh JJ*. EGR-1 plays a protective role in AMPK inhibitor compound C-induced apoptosis through ROS-induced ERK activation in skin cancer cells. Oncology Letters. 2021, 21(4): 304. (SCI, impact factor: 2.311, Ranking: 182/244 ONCOLOGY).*Corresponding author.

Chung MC, Yu TM, Wu MJ, Chuang YW, Muo CH, Chen CH, Chang CH, Shieh JJ, Hung PH, Chen JW, Chung CJ. Is combined peritoneal dialysis and hemodialysis redundant? A nationwide study from Taiwan. BMC Nephrol. 2020, 21(1): 348. (SCI, impact factor: 1.43).

Kao JK, Wang SC, Ho LW, Huang SW, Lee CH, Lee MS, Yang RC, Shieh JJ*. M2-like polarization of THP-1 monocyte-derived macrophages under chronic iron overload. Annals of Hematology. 2020, 99(3):431-441. (SCI, impact factor: 2.904, Ranking: 35/76 HEMATOLOGY). *Corresponding author.

Wang ST, Huang SW, Liu KT, Lee TY, Shieh JJ*, Wu CY*. Atorvastatin-induced senescence of hepatocellular carcinoma is mediated by downregulation of hTERT through the suppression of the IL-6/STAT3 pathway. Cell Death Discovery. 2020, 6:17. (SCI, impact factor: 4.114, Ranking: 76/195 Cell Biology) *Corresponding author.

Chuang KC, Chang CR, Chang SH, Huang SW, Chuang SM, Li ZY, Wang ST, Kao JK, Chen YJ, Shieh JJ*. Imiquimod-induced ROS production disrupts the balance of mitochondrial dynamics and increases mitophagy in skin cancer cells. Journal of Dermatological Science. 2020, 98(2): 152-162.(SCI, impact factor: 3.681, Ranking: 12/68 DERMATOLOGY) *Corresponding author.

Huang SW, Wang ST, Chang SH, Chung KC, Wang HY, Kao JK, Liang SM, Wu CY, Kao SF, Chen YJ, Shieh JJ*. Imiquimod exerts antitumor effects by inducing immunogenic cell death and is enhanced by the glycolytic inhibitor 2-deoxy-glucose. Journal of Investigative Dermatology. 2020, 140: 1771-1783. (SCI, impact factor: 7.143, Ranking: 3/68 DERMATOLOGY). *Corresponding author.

Kao JK, Hsu TF, Lee MS, Su TC, Lee CH, Hsu CS, Shieh JJ, Wang JY, Yang RC. Subcutaneous injection of recombinant heat shock protein 70 ameliorates atopic dermatitis skin lesions in a mouse model.Kaohsiung J Med Sci. 2020, 36: 186-195. (SCI, impact factor: 1.737, Ranking: 107/138 MEDICINE, RESEARCH & EXPERIMENTAL) .

Chen YJ*, Ho HJ, Tseng CH, Lai ZL, Shieh JJ, Wu CY. Intestinal microbiota profiling and predicted metabolic dysregulation in psoriasis patients. Exp Dermatol. 2018, 27(12): 1336-1343. (SCI, impact factor: 3.368, Ranking:15/68 DERMATOLOGY) .

Chang SH, Huang SW, Wang ST, Chung KC, Hsieh CW, Kao JK, Chen YJ, Wu CY*, Shieh JJ*. Imiquimod-induced autophagy is regulated by ER stress-mediated PKR activation in cancer cells. Journal of Dermatological Science. 2017, 87(2):138-148. (SCI, impact factor: 3.739, Ranking: 7/61 DERMATOLOGY) *Corresponding author.

Wu CY, Chang YT, Juan CK, Shieh JJ, Lin YP, Liu HN, Lin JT, Chen YJ. Risk of inflammatory bowel disease in rosacea patients: results from a nationwide cohort study. Journal of the American Academy of Dermatology. 2017, 76: 911-917. (SCI, impact factor: 5.621, Ranking: 3/61 DERMATOLOGY)

Kao JK, Shieh JJ, Lee CH, Lee MS, Hsu TF, Yang RC. Potential treatments for atopic dermatitis. Journal of Antivirals and Antiretrovirals. 2017, Accepted. (review)

Wang ST, Ho HJ, Lin JT, Shieh JJ*, Wu CY*. Simvastatin-induced cell cycle arrest though inhibition of STAT3/SKP2 axis and activation of AMPK to promote p27 and p21 accumulation in hepatocellular carcinoma cells. Cell Death and Disease. 2017, 8, e2626. (SCI, impact factor: 5.378, Ranking: 38/187 Cell Biology) *Corresponding author.

Huang SW, Chen YJ, Wang ST, Ho LW, Kao JK, Takahashi M, Narita M, Wu CY, Cheng HY, Shieh JJ*. Azithromycin Impairs TLR7 Signaling in Dendritic Cells and Improves the Severity of Imiquimod-Induced Psoriasis-Like Skin Inflammation in Mice. Journal of Dermatological Science. 2016, 84(1): 59-70. (SCI, impact factor: 3.739, Ranking: 7/61 DERMATOLOGY) *Corresponding author.

Kao JK, Wang SC, Ho LW, Huang SW, Chang SH, Yang RC, Ke YY, Wu CY, Wang JY*, Shieh JJ*. Chronic Iron Overload Results in Impaired Bacterial Killing of THP-1 Derived Macrophage through the Inhibition of Lysosomal Acidification. Plos One. 2016, 11(5): e0156713 (SCI, impact factor: 3.234, Ranking: 9/57 MULTIDISCIPLINARY SCIENCES) *Corresponding author.

Wu CY, Chang YT, Juan CK, Shen JL, Lin YP, Shieh JJ, Liu HN, Chen YJ*. Depression and insomnia in patients with psoriasis and psoriatic arthritis taking tumor necrosis factor antagonists. Medicine. 2016, 95(22):e3816. (SCI, impact factor: 5.723, Ranking: 15/153 MEDICINE, GENERAL & INTERNAL)

Huang SW, Chang SH, Mu SW, Jiang HY, Wang ST, Kao JK, Huang JL, Wu CY, Chen YJ, Shieh JJ*. Imiquimod activates p53-dependent apoptosis in a human basal cell carcinoma cell line. Journal of Dermatological Science. 2016, 81(3): 182-91. (SCI, impact factor: 3.419, Ranking: 9/62 DERMATOLOGY) *Corresponding author.

Daniel J. Klionsky and 2170 others. Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition). Autophagy. 2016; 12(1): 1-222. (review; SCI, impact factor: 11.753, Ranking: 15/184 CELL BIOLOGY)

Kao JK, Lee CH, Lee MS, Hsu CS, Tsao LY, Tsai YG, Shieh JJ*, Yang RC*. Heat shock pretreatment reduces expression and release of TSLP from keratinocytes under Th2 environment. Pediatric Allergy and Immunology. 2016; 27(1): 62-9. (SCI, impact factor: 3.397, Ranking: 9/119 PEDIATRICS) *Corresponding author.

Wang ST, Huang SW, Kao JK, Liang SM, Chen YJ, Chen YY, Wu CY, Shieh JJ*. Imiquimod-induced AMPK activation causes translation attenuation and apoptosis but not autophagy. Journal of Dermatological Science. 2015; 78(2)108~116 (SCI, impact factor: 3.335, Ranking: 9/61 DERMATOLOGY)*Corresponding author.

Chang CH, Chan PC, Li JR, Chen CJ, Shieh JJ, Fu YC, Chen HC, Wu MJ. Gab1 is essential for membrane translocation, activity and integrity of mTORCs after EGF Stimulation. Oncotarget. 2015; (6)3:1478~1489 (SCI, impact factor: 6.627, Ranking: 17/202 ONCOLOGY)

Wu CY, Shieh JJ, Shen JL, Liu YY, Chang YT, Chen YJ. Association between anti-diabetic drugs and psoriasis risk in diabetic patients: results from a nationwide nested case control study. Journal of the American Academy of Dermatology. 2015; 72(1):123~130. (SCI, impact factor: 5.004, Ranking: 3/61 DERMATOLOGY)

Huang SW, Kao JK, Wu CY, Wang ST, Lee HC, Liang SM, Chen YJ, Shieh JJ*. Targeting aerobic glycolysis and HIF-1 alpha expression enhance imiquimod0induced apoptosis in cancer cells. Oncotarget, 2014 , 5(5): 1363-1381.(SCI, impact factor: 6.636, Ranking: 21/197 ONCOLOGY) *Corresponding author.

Yang SY, Wang HM, Wu TW, Chen YJ, Shieh JJ, Lin JH, Ho TF, Luo RJ, Chen CY, Chang CC. Chang CC. Subamolide B Isolated from Medicinal Plant Cinnamomum subavenium Induces Cytotoxicity in Human Cutaneous Squamous Cell Carcinoma Cells through Mitochondrial and CHOP-Dependent Cell Death Pathways. Evid Based Complement Alternat Med. 2013;2013:630415.(SCI, impact factor: 4.774, Ranking: 1/22 INTEGRATIVE & COMPLEMENTARY MEDICINE)

Huang SW, Wu CY, Wang YT, Kao JK, Lin CC, Chang CC, Mu SW, Chen YY, Chiu HW, Chang CH, Liang SM, Chen YJ, Huang JL, Shieh JJ*. p53 modulates the AMPK inhibitor compound C induced apoptosis in human skin cancer cells. Toxicology and Applied Pharmacology. 2013, 267: 113-124. (SCI, impact factor: 4.447, Ranking:10/83 TOXICOLOGY) *Corresponding author.

Shieh JJ, Lu YH, Huang SW, Huang YH, Sun CH, Chiou HJ, Liu C, Lo MY, Lin CY, Niu DM. Misdiagnosis as steatohepatitis in a family with mild glycogen storagedisease type 1a. Gene. 2012; 509(1): 154-7 (SCI, impact factor: 2.341, Ranking: 92/157 GENETICS & HEREDITY)

Chen HP#, Shieh JJ#, Chang CC, Chen TT, Lin JT, Wu MS, Lin HJ, Wu CY. Metformin decreases hepatocellular carcinoma risk in a dose-dependent manner: population-based and in vitro studies. Gut. 2013; 62(4):606-615. (SCI, impact factor: 10.614, Ranking: 3/72 GASTROENTEROLOGY & HEPATOLOGY) #Co-first auther.

Daniel J. Klionsky and 1268 others. Guidelines for the use and interpretation of assays for monitoring autophagy. Autophagy. 2012; 8(4): 445-544. (review; SCI, impact factor: 6.643, Ranking: 34/178 CELL BIOLOGY)

Hsieh HY, Shieh JJ, Chen CJ, Pan MY, Yang SY, Lin SC, Chang JS, Lee AY, Chang CC. Prodigiosin down-regulates SKP2 to induce p27(KIP1) stabilization and antiproliferation in human lung adenocarcinoma cells. Br J Pharmacol. 2012; 166:2095-2108 (SCI, impact factor:4.925, Ranking: 19/252 Pharmacology & pharmacy)

Huang SW, Chang CC, Lin CC, Tsai JJ, Chen YJ, Wu CY, Liu KT, Shieh JJ*. Mcl-1 determines the imiquimod-induced apoptosis but not imiquimod-induced autophagy in skin cancer cells. Journal of Dermatological Science. 2012; 65(3):170-8 (SCI, impact factor: 3.712, Ranking: 7/54 DERMATOLOGY)

Wu CS#, Chen YJ#, Chen JJ, Shieh JJ, Huang CH, Lin PS, Chang GC, Chang JT, Lin CC. Terpinen-4-ol Induces Apoptosis in Human Nonsmall Cell Lung Cancer In Vitro and In Vivo. Evid Based Complement Alternat Med. 2012; 2012:818261 (SCI, impact factor: 2.964, Ranking: 3/19 Integrative & Complementary Medicine) #Co-first auther.

Huang SW, Liu KT, Chang CC, Chen YJ, Wu CY, Tsai JJ, Lu WC, Wang YT, Liu CM, Shieh JJ*. Imiquimod simultaneously induces autophagy and apoptosis in human basal cell carcinoma cells. Brit J Dermatol. 2010; 163(2): 310-20 (SCI, impact factor: 4.351, Ranking: 3/54 DERMATOLOGY)

Shieh JJ*, Liu KT, Huang SW, Chen YJ, Hsieh TY. Modification of alternative splicing of Mcl-1 pre-mRNA using antisense morpholino oligonucleotides induces apoptosis in basal cell carcinoma cells. J Invest Dermatol. 2009; 129(10):2497-506 (SCI, impact factor: 6.270, Ranking: 1/53 DERMATOLOGY)

Lin MT, Shieh JJ, Chang JHM, Chang SW, Chen TC, Hsu WH. Early detection of adrenocortical carcinoma in a child with Li-Fraumeni syndrome. Pediatric Blood & Cancer. 2009; 52(4): 541-544. (SCI, impact factor:2.134, Ranking: 25/94 PEDIATRICS)

Chiou YL, Shieh JJ, Lin CY. Blocking of Akt/NF-kappaB signaling by pentoxifylline inhibits platelet-derived growth factor-stimulated proliferation in Brown Norway rat airway smooth muscle cells. Pediatr Res. 2006;60(6):657-62. (SCI, impact factor: 2.607, Ranking:14/94 PEDIATRICS)

Tsai YG, Chien JW, Chen WL, Shieh JJ, Lin CY. Induced apoptosis of TH2 lymphocytes in asthmatic children treated with Dermatophagoides pteronyssinus immunotherapy. Pediatr Allergy Immunol. 2005;16(7):602-8. (SCI, impact factor: 2.676, Ranking:11/94 PEDIATRICS )

Nguyen AD, Pan CJ, Shieh JJ, Chou JY: Increased cellular cholesterol efflux in glycogen storage disease type Ia mice: a potential mechanism that protects against premature atherosclerosis. FEBS letters 2005; 579(21):4713-8.(SCI, impact factor: 3.541, Ranking: 20/74 BIOPHYSICS)

Shieh JJ, Pan CJ, Mansfield BC, Chou JY: In islet-specific glucose-6-phosphatase-related protein, the beta cell antigenic sequence that is targeted in diabetes is not responsible for the loss of phosphohydrolase activity. Diabetologia. 2005; 48(9):1851-9. (SCI, impact factor: 6.551, Ranking: 9/105 ENDOCRINOLOGY & METABOLISM )

Shieh JJ, Pan CJ, Mansfield BC, Chou JY : A potential new role for muscle in blood glucose homeostasis. J Biol Chem 2004; 279(25):26215-26219. (SCI, impact factor: 5.328, Ranking: 48/283 BIOCHEMISTRY & MOLECULAR BIOLOGY )

Shieh JJ, Pan CJ, Mansfield BC, Chou JY: The islet-specific glucose-6-phosphatase-related protein, implicated in diabetes, is a glycoprotein embedded in the endoplasmic reticulum membrane. FEBS letters 2004; 562:160-164. (SCI, impact factor: 3.541, Ranking: 20/74 BIOPHYSICS )

Ghosh A, Shieh JJ, Pan CJ, Chou JY: Histidine-167 is the phosphate acceptor in glucose-6-phosphatase-beta forming a phosphohistidine-enzyme intermediate during catalysis. J Biol Chem 2004; 279(13): 12479-12483. Co-first auther. (SCI, impact factor: 5.328, Ranking: 48/283 BIOCHEMISTRY & MOLECULAR BIOLOGY)

Shieh JJ, Pan CJ, Mansfield BC, Chou JY: A glucose-6-phosphate hydrolase, widely expressed outside the liver, can explain age-dependent resolution of hypoglycemia in glycogen storage disease type Ia. J Biol Chem 2003; 278(47): 47098-47103. (SCI, impact factor: 5.328, Ranking: 48/283 BIOCHEMISTRY & MOLECULAR BIOLOGY)

Wang JH, Liang CM, Peng JM, Shieh JJ, Jong MH, Lin YL, Sieber M, Liang SM: Induction of immunity in swine by purified recombinant VP1 of foot-and-mouth disease virus. Vaccine 2003; 21:3721-9. (SCI, impact factor: 3.616, Ranking: 20/92 MEDICINE, RESEARCH & EXPERIMENTAL)

Chen LY, Shieh JJ, Lin B, Pan CJ, Gao JL, Murphy PM, Roe TF, Moses S, Ward JM, Lee EJ, Westphal H, Mansfield BC, Chou JY: Imapired glucose homeostasis, neutrophil recruitment, chemokine action and calcium flux in glycogen storage disease type 1b mice. Hum Mol Genet 2003; 12: 2547-2558. #Co-first auther. (SCI, impact factor: 7.386, Ranking: 13/144 GENETICS & HEREDITY)

Chen LY, Pan CJ, Shieh JJ, Chou JY: Structure-function analysis of the glucose-6-phosphate transporter deficient in glycogen storage disease type Ib. Hum Mol Genet 2002; 11: 3199-3207. (SCI, impact factor: 7.386, Ranking: 13/144 GENETICS & HEREDITY)

Sun MS, Pan CJ, Shieh JJ, Ghosh A, Chen LY, Mansfield BC, Ward JM, Byrne BJ, Chou JY: Sustained hepatic and renal glucose-6-phosphatase expression corrects glycogen storage disease type Ia in mice. Hum Mol Genet 2002; 11: 2155-2164. (SCI, impact factor: 7.386, Ranking: 13/144 GENETICS & HEREDITY)

Ghosh A, Shieh JJ, Pan CJ, Sun MS, Chou JY: The catalytic center of glucose-6-phosphatase: His176 is the nucleophile forming the phosphohistidine-enzyme intermediate during catalysis. J Biol Chem 2002; 277: 32837-32842. (SCI, impact factor: 5.328, Ranking: 48/283 BIOCHEMISTRY & MOLECULAR BIOLOGY )

Shieh JJ, Teraioglu M, Hirawa H, Marsh J, Pan CJ, Chen LY, Chou JY: The molecular basis of glycogen storage disease type 1a: structural and functional analysis of mutants in glucose-6-phosphatase. J Biol Chem 2002; 277: 5047-5053. (SCI, impact factor: 5.328, Ranking: 48/283 BIOCHEMISTRY & MOLECULAR BIOLOGY )

Shieh JJ, Liang CM, Chen CY, Lee F, Jong MH, Lai SS, Liang SM: Enhancement of the immunity to foot-and-mouth disease virus by DNA priming and protein boosting immunization. Vaccine 2001; 19: 4002-4010. (SCI, impact factor: 3.616, Ranking: 20/92 MEDICINE, RESEARCH & EXPERIMENTAL)

Shieh JJ, Lin CY: A frequent mutation in Chinese patients with infantile type of GSD II in Taiwan: Evidence for a founder effect. Hum Mutat 1998; 11:306-312. (SCI, impact factor: 6.887, Ranking: 16/144 GENETICS & HEREDITY)

Shieh JJ, Lin CY: Identification of a small deletion in one allele of patients with infantile form of glycogen storage disease type II. Bioche Biophy Res Commu 1996; 219: 322-326. (SCI, impact factor: 2.548, Ranking: 40/74 BIOPHYSICS)

Lin CY, Shieh JJ: Molecular study on the infantile form of Pompe disease in Chinese in Taiwan. Acta Paed Sin 1996; 37:115-121.

Lin CY, Shieh JJ: Identification of a de novo point mutation resulting in infantile form of Pompe’s disease. Bioche Biophy Res Commu 1995; 208:886-893. (SCI, impact factor: 2.548, Ranking: 40/74 BIOPHYSICS)

Shieh JJ, Wang LY, Lin CY: Point mutation in Pompe disease in Chinese. J Inher Metab Disease 1994; 17:145-148. (SCI, impact factor: 3.598, Ranking: 44/144GENETICS & HEREDITY)


International Conference Presentation:

Shieh, J.J., Huang, S.W., The TLR7 agonist imiquimod triggers immunogenic cell death in cancer cells. In: 2017 the Japanese Society of Medical Oncology Annual Meeting. Kobe, Japan, July 27-29, 2017.

Chang, S.H., Shieh, J.J., Imiquimod induces ER stress and PKR-mediated autophagy via ROS production in cancer cells. In: Frontiers in Cancer Science 2015. Singapore, November 2-4, 2015.

Wang, S.T., Shieh, J.J., Wu, C.Y., Statins inhibit hepatocellular carcinoma progression: population-based and in vitro studies. In: Frontiers in Cancer Science 2015. Singapore, November 2-4, 2015.

Huang, S.W., Wang, S.T., Wu, C.Y., Chen, Y.J., Shieh, J.J., Imiquimod activates p53-dependent apoptosis in human skin cancer cells. In: Frontiers in Cancer Science 2015. Singapore, November 2-4, 2015.

Huang, S.W., Shieh, J.J., The antibiotic azithromycin improves the severity with imiquimod-induced psoriasis like skin inflammation in mice. In: 39th Annual Meeting of the Japanese Society for Investigative Dermatology. Osaka, Japan, December 12-14, 2014.

Wang, S.T., Shieh, J.J., Huang, S.W., Wu, C.Y., IMQ induced AMPK activation causes translation inhibition and apoptosis but not autophagy. In: 39th Annual Meeting of the Japanese Society for Investigative Dermatology. Osaka, Japan, December 12-14, 2014.

Chang, S. H., Shieh, J.J., Huang, S.W., Imiquimod induces STAT3-mediated autophagy via ROS production in cancer cells. In: 39th Annual Meeting of the Japanese Society for Investigative Dermatology. Osaka, Japan, December 12-14, 2014.

Shieh, J.J., Huang, S.W., Imiquimod Induces HIF-1 alpha Expression and Aerobic Glycolysis to Protect Imiquimod-induced Apoptosis in Cancer Cells. In: The 6th Annual Asian Oncology Summit (AOS) and 10th Annual Conference of the Organisation for Oncology and Translational Research (OOTR), Kuala Lumpur, Malaysia, April 11-13, 2014.

Chen, Y.J., Huang S.W., Wang, S.T., Cheng, H.Y., Shieh, J.J. Azithromycin improves imiquimod-induced psoriasis-like skin inflammation. In:The 8th International Congress on Cutaneous Adverse Drug Reactions and The 39th Annual Meeting of the Taiwanese Dermatological Association. Chang-Gung University, Taiwan, November 16-17, 2013.

Huang, S.W., Chen, Y.J., Cheng, H.Y., Wang, S.T., Shieh, J.J. Antibiotic Azithromycin improves the severity of mice with imiquimod-induced psoriasis like skin inflammation. In: 2013 Asia Pacific Congress of Allergy, Asthma and Clinical Immunology. Taipei, Taiwan, November 14-17, 2013.

Shieh, J.J., Huang, S.W., The glucose availability and the induction of HIF-1 alpha expression determine thee imiquimod induced apoptosis in cancer cells. In: 37th Annual Meeting of the Japanese Society for Investigative Dermatology. Okinawa, Japan, December, 7-9, 2012.

Shieh, J.J., Huang, S.W., Mu, S.W., Chen, Y.Y. p53 modulates the AMPK inhibitor compound C induced apoptosis in human skin cancer cells. In: 36th Annual Meeting of the Japanese Society for Investigative Dermatology. Kyoto, Japan, December, 9-11, 2011.

Huang, S.W., Shieh, J.J. Mcl-1 over-expression causes resistance to imiquimod-induced apoptosis but not imiquimod-induced autophagy in basal cell carcinoma cells. In 22nd World Congress of Dermatology.Seoul, Korea, May, 24-29, 2011. (Silver Award of E. Poster)

Huang, S.W., Liu, K.T., Shieh, J.J. The Interplay between Imiquimod Induced Autophagy and Apoptosis in Human Basal Cell Carcinoma Cells. In: 34th Annual Meeting of the Japanese Society for Investigative Dermatology. Fukuoka, Japan, December, 4-6, 2009.

Shieh, J.J., Chen, C.T., Huang, W.R. The variant glucose-6-phosphate transporter decreases protein stability and requires MyoD-dependent alternative splicing during myogenesis of muscle cells. Experimental Biology 2007 Annual Meeting. Washington D.C., USA, April 28-May 2, 2007.

Shieh, J.J., Lin, C.Y. Identification of novel splicing variants of the human Na+/Pi cotransporter 4 in human kidney. Experimental Biology 2005 Annual Meeting and the XXXV International Congress of Physiological Sciences. San Diego, California, USA, April 2-6, 2005.

Shieh, J.J., Terzioglu, M., Pan, C.J., Chen, L.Y., Hirawa, H., Chou, J.Y. The Molecular basis of glycogen storage disease type 1a: structural and functional analysis of mutations in glucose-6-phosphatase. The 51st Annual Meeting of the American Society of Human Genetics. San Diego, California, USA, October 12-16, 2001.

Shieh, J.J., Liang, C.M., Wang, J.H., Kao, K., Chen, C.Y., Yang, N.S., Liang, S.M. Immune responses induced by FMDV VP1 DNA priming and protein boosting. 1999 Winter Biotechnology Conference at Cold Spring Harbor Meeting on Molecular Approaches to Vaccine Design. Cold Spring Harbor, New York, USA, December 2-5, 1999.

Shieh, J.J., Lin, C.Y. Frequent mutation in Chinese patients with infantile type of GSD II in Taiwan: evidence for a founder effect. Acid Maltase Deficiency Association Conference. San Antonio, Texas, USA, June 23-25, 1997.

Shieh, J.J., Lin, C.Y. Molecular study of Pompe’s disease in Chinese. The 6th International Congress of Inborn Errors of Metabolism. Milano, Italy, May 27-31, 1994.

專利/技術轉移

1. Liang SM, Wang JH, Shieh JJ (2007): VP1 of foot-and-mouth disease virus. (US patent 7,217,784).

2. Liang SM, Wang JH, Shieh JJ (2007): VP1 of foot and mouth disease. (中華民國專利 I-285111號).