張以承博士
合聘副研究員
- 02-23123456 ext 88656 (NTU) (Lab) (Room No: 343)
- 02-33936523 (Fax)
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Specialty:
- Diabetes and Obesity
- Genetic epidemiology
Education and Positions:
Education:
M.D. -National Taiwan University
Ph.D. -Academia Sinica and National Taiwan University Joint Ph.D. Program of Translational Medicine
Position:
- Associate Professor, Graduate Institute of Medical Genomics and Proteomics, Medical College, National Taiwan University
- Attending Physician, Department of Endocrinology and Metabolism, National Taiwan University Hospital
- Vice CEO, Center for Bariatric and Metabolic Surgery, National Taiwan University Hospital
實驗室主要研究重點是（1）第2型糖尿病、肥胖、血壓、腎功能的基因研究, 特別是東亞特有之遺傳位點（2）第2型糖尿病、肥胖、血壓、腎功能的轉譯研究: 以轉殖基因小鼠模型中進一步驗證人類基因研究所找到的第 2 型糖尿病、肥胖、血壓、與腎功基因位點、闡明分子機制、並開發藥物, 進行臨床試驗。
1. 第2型糖尿病、肥胖、血壓、腎功能的人類和小鼠基因研究
(1) 東亞族群在基因體學上,為相對獨立的族群。我們首度探討TCF7L2基因變異與糖尿病在華人的關連與機制(Diabetes 56:2631-7, 2007; Diabetes 56:e23, 2007; Journal Clinical Endocrinology Metabolism 94:3575-82, 2009; Journal of Molecular Medicine 88:183-92, 2010 )。以及FTO基因多型性與肥胖在東亞族群的相關((Diabetes 56:2631-7, 2007; Diabetes 56:e23, 2007; Journal Clinical Endocrinology Metabolism 94:3575-82, 2009; Journal of Molecular Medicine 88:183-92, 2010; Diabetologia 55:981-95, 2012)，發展並驗證「臺灣糖尿病風險預測指標」，預測糖尿病風險達75%準確度 (Diabetes Care 32: 2294-6, 2009; Diabetes Care 33:e26, 2010)，後來並加入polygenic score建立起華人第一個糖尿病多基因預測預測指標(Clinical Endocrinology 76:365-72, 2012; PLoS One 9(4):e95045, 2014;)，我們也與賴台軒教授團隊, 中研院熊嘉妮老師合作找尋到華人腎功能與白蛋白尿的新位點(American Journal of Nephrology 2024; 21:1-13. Am J of Nephrology 2023;54(9-10):359-3692. Mayo Clinic Proceedings 2023;98(4):513-521.)。
(2) 參與大規模東亞全基因體掃描合作計畫, 如Trans-Omics for Precision Medicine WGS-About TOPMed (TOPMed), Stanford-Asian Pacific Program in Hypertension and Insulin Resistance (SAPPHIRe)，發現許多新穎的東亞糖尿病致病基因如ALDH2, G6PD (Nature Genetics 44:67-72, 2011; Nature Genetics 46: 234–244, 2014; Human Molecular Genetics. 23:1108-1119, 2014; Am J Hum Genet. 109(1):81-96, 2022; Nature. 586: 763–768, 2020; Nat Genet.52:969-983, 2020; Nat Communications 12:2182, 2021; Nat Genet. 53:840-860, 2021; Nature 590:290-299,2021; Clin J Am Soc Nephrol. 16:287-289,2021 Nat Commun. 12:3626. 2021; Nat Genet. 53:1504-1516,2021 ;BMC Genomics 23:148,2022.)。並以台灣人體生物資料庫找尋到決定血清中FGF21, FGF23, 昇糖素以及影響退褪黑激素之基因位點 (Scientific Reports 10:14578, 2020; Scientific Reports 12:8025, 2022) 。
(3) 東亞糖尿病病患以發病年齡早, 併發症提前發生為特徵 (Asian Phenotype), 我們與敏盛醫院合作, 以次世代定序找尋早發型糖胖症(Diabesity)家族之基因。並找尋預測減重手術效果之基因位點。
(4) 我們與賓州大學團隊合作, 發現特定粒線體單套型與肥胖有關(Biochim Biophys Acta Bioenergetics 1859:878-892, 2018)。
(5) 我們也發現東亞特有之乙醛去氫酶(ALDH2)變異，在Aldh2小鼠嵌入鼠模式中，會導致肥胖、血糖異常、脂肪肝與腎功能異常，這些發現陸續被後來的大規模的人類全基因組掃描所證實。我們也與史丹佛大學團隊與製藥公司合作，發展出可以降低有害酫類的口服、水溶性、高度專一性ALDH2促進劑，可預防高脂高蔗糖餵食小鼠的體重增加、改善血糖與脂肪肝。 除此之外, ALDH2促進劑也可有效治療多種急性腎損傷模式，並可預防小鼠糖尿病慢性腎病變，改善糖尿病心肌病變, 其中急性腎衰竭之預防效果 (BMC Cardiovascular Disorders 29;12:58, 2012; Antioxidants 2021, 10(3), 450; Nature Communication 2023; 14(1):5971)。
(6) 我們發現Gpx7基因剔除鼠產生肥胖，此研究証實氧化壓力在脂肪細胞分化具有正向的調控角色，以及N-acetylcysteine的減重效果 (EMBO Molecular Medicine 5:1165–1179, 2013), 並探討此基因抗氧化之分子機轉(Molecular Cell 48:747-59, 2012)
(7) 我們經由大規模家族血壓之連鎖分析, 發内質網蛋白基因RRBP1與血壓有關, 並發現RRBP1會調節腎素在內質網的運輸, 為腎素調節之新機轉。
(8) 我們與史丹佛大學團隊合作, 我們發現模擬廣東型蠶豆症的基因嵌入鼠，易產生肥胖、高血糖, 脂肪肝, 心臟衰竭, 與腎小管壞死, 將以G6PD促進劑AG1, 驗證其療效。
(9)基因相關研究發現血癌基因TRIB2會影響脂肪分布，並與人類遷徙與產熱有關，我們與中研院生醫所嚴仲陽合作, 以Trib2基因剔除鼠印證此發現。
(9) 我們與分醫所劉雅雯老師合作發現調GSK3α控肌肉細胞葡萄糖攝取之新機轉, 並以小分子抑制劑與基因剔除鼠驗證。
(10) 我們與中研院基因體中心洪上程老師, 合作發現葡萄糖高分子聚合物，可以有效吸腸道油脂，達成小鼠減重與降血脂效果。
3. 代謝內分泌的臨床與流行病學研究
(1) 我們和敏盛醫院李威傑老師, 合作Taiwan Diabesity Study,追蹤肥胖糖尿病患接受減重手術2年後各種糖尿病併發症, 發現接受手術者腎臟功能與神經病變均有改善, 基於一系列減重手術的研究(Asian J Surg 42:244-250, 2019; Obesity Surgery 31:117-126, 2021; BMJ Open 5:e006964, 2015), 於2016年於美國糖尿病年會受邀invited lecture。我們也發現胃繞道手術相對於限制型手術, 有獨立於體重脂降血糖與降血脂效果, 我們正針對膽胰脂(bilio-pancreatic limb)與膽酸的作用進一步探討
(2)我們與公衛學院杜裕康老師與張家勳教授合作, 發現即使是正常值以內的甲狀腺功能偏低, 都與代謝症候群以及腎功能有關(J Clin Med 8, 817, 2019; Scientific Reports 8: 2031, 2018; Am J Nephrol 49:41–51, 2019)
(3)我們與公衛學院林先和老師合作, 研究糖尿病前期與肥胖對於感染的作用(Open Forum Infectious Diseases 8(1) ofaa545,2021; Scientific Reports. 10:4475, 2020; Clinical Infectious Disease 66:699-705.2019)以及結核菌感染風險(International Journal of Epidemiology 52(3):932-941, 2022) 。
(4)我們與台大眼科部廖述朗老師與竹北分院呂菁老師合作, 以質譜儀分析甲狀腺病變病患眼部發炎脂肪之變化, 初步發現與前列腺素代謝有關。
期刊 136
專書 5
期刊 136 專書 5
- (Chang Yi-Cheng), Hsieh Meng-Lun, Lee Hsiao-Lin, Hee Siow-Wey, Chang Chi-Fon, Yen Hsin-Yung, Chen Yi-An, Chen Yet-Ran, Chou Ya-Wen, Li Fu-An, Ke Yi-Yu, Chen Shih-Yi, Hung Ming-Shiu, Hung Alfur Fu-Hsin, Huang Jing-Yong, Chiu Chu-Hsuan, Lin Shih-Yao, Shih Sheue-Fang, Hsu Chih-Neng, Hwang Juey-Jen, Yeh Teng-Kuang, Rachel Cheng Ting-Jen, Liao Karen Chia-Wen, Laio Daniel, Lin Shu-Wha, Chen Tzu-Yu, Hu Chun-Mei, Vogel Ulla, Saar Daniel, Kragelund Birthe B., Tsou Lun Kelvin, Tseng Yu-Hua, Chuang Lee-Ming Identification of PTGR2 inhibitors as a new therapy for diabetes and obesity. EMBO MOLECULAR MEDICINE (2024-12-20) [JCR] [WOS]
- Lin, H. H., Yu, I. S., Cheng, M. S., Chang, T. J., Lin, H. Y., (Chang, Y. C.), [...], Huang, H. P., Lee, M. S. Spint1 disruption in mouse pancreas leads to glucose intolerance and impaired insulin production involving HEPSIN/MAFA. NATURE COMMUNICATIONS 15(1), 15-10537 (2024-12-03) [JCR] [WOS]
- Wu Cyun-Ming, Li Hao-Yun, Li Wen-Yi, Hsu Chih-Neng, Yang Wei-Shun, Chuang Gwo-Tsang, Che Tony Pan-Hou, Lee Tung-Yuan, Lee Hsiao-Lin, Hee Siow-Wey, Lee Jiin-Horng, Liao Daniel, Liao Karen Chia-Wen, Liu Ya-Wen, Hsuan Chin-Feng, Chang Yi-Cheng, Chu Shao-Lun Protocol to measure glucose utilization in mouse tissues using radiolabeled 2-deoxy-D-glucose. STAR Protocols 5(4), 103478 (2024-12) [JCR] [WOS]
- Chuang Gwo-Tsann, Hsiung Chia-Ni, Che Tony Pan-Hou, Chang Yi-Cheng Discovering Novel Loci of Chronic Kidney Disease via Principal Component Analysis-Based Multiple-Trait Genome-Wide Association Study. American Journal of Nephrology Online ahead of print., 1-13 (2024-10-21) [JCR] [WOS]
- Liu Chia-Ju, Chen Jien-jiun, Wu Jo-Hsuan, Chung Yao-Te, Chen Jin-Wun, Liu Meng-Tsun, Chiu Chu-Hsuan, Chang Yi-Cheng, Chang Sheng-Nan, Lin Jou-Wei, Hwang Juey-Jen Association of exosomes in patients with compromised myocardial perfusion on functional imaging. Journal of the Formosan Medical Association 123(9), 968-974 (2024-09) [JCR] [WOS]
- Takahashi Nagahide, Nishimura Tomoko, Okumura Akemi, Harada Taeko, Iwabuchi Toshiki, Rahman Md Shafiur, Liu Pi-Hua, Chuang Gwo-Tsann, Chang Yi-Cheng, Nomura Yoko, Tsuchiya Kenji J. Association between genetic risk of melatonin secretion and attention deficit hyperactivity disorder. Psychiatry Research Communications 4(3), 100188 (2024-07-30) [JCR] [WOS]
- Keener R, [...], Chang YC, [...], Battle A. Validation of human telomere length multi-ancestry meta-analysis association signals identifies POP5 and KBTBD6 as human telomere length regulation genes. NATURE COMMUNICATIONS 15(1), 15-4417 (2024-05-24) [JCR] [WOS]
- Tsao Hsiao-Mei, Lai Tai-Shuan, (Chang Yi-Cheng), Hsiung Chia-Ni, Tsai I-Jung, Chou Yu-Hsiang, Wu Vin-Cent, Lin Shuei-Liong, Chen Yung-Ming A multi-trait GWAS identifies novel genes influencing albuminuria. Nephrology Dialysis Transplantation 40(1), 123-132 (2024-05-21) [JCR] [WOS]
- Hee Siow-Wey, Chang Yi-Cheng, Su Lynn, Chen Ing-Jung, Jeng Yung-Ming, Hsieh Meng-Lun, Chang Yu-Chia, Li Fu-An, Liao Daniel, Chen Shiau-Mei, Chuang Lee-Ming 15-keto-PGE2 alleviates nonalcoholic steatohepatitis through its covalent modification of NF-κB factors. iScience 26(10), 107997 (2023-10) [JCR] [WOS]
- Chang Yi-Cheng, Lee Hsiao-Lin, Yang Wenjin, Hsieh Meng-Lun, Liu Cai-Cin, Lee Tung-Yuan, Huang Jing-Yong, Nong Jiun-Yi, Li Fu-An, Chuang Hsiao-Li, Ding Zhi-Zhong, Su Wei-Lun, Chueh Li-Yun, Tsai Yi-Ting, Chen Che-Hong, Mochly-Rosen Daria, Chuang Lee-Ming A common East-Asian ALDH2 mutation causes metabolic disorders and the therapeutic effect of ALDH2 activators. Nature Communications 14(1), 1-16 (2023-09-25) [JCR] [WOS]
- 博士後研究 -
李曉苓
李曉苓
- E-mail:
- 研究助理 -
- 學生 -
李東原
李東原
- Tel: 02-2652-3071
- E-mail:
莊國璨
莊國璨
- Tel: 02-2652-3071
楊為舜
楊為舜
- Tel: 02-23123456 ext 88666
- E-mail: weishun.yang@gmail.com
謝奔浩
謝奔浩
- Tel: 02-23123456 ext 88666
- E-mail: tonyche12o5@gmail.com
- 昔日夥伴 -
1. 1998 臺灣大學醫學系書卷獎
2. 2004 臺大內科住院醫師學術優異獎
3. 2006 國衛院醫師攻讀臨床在職專班獎助
4. 2007 中華民國糖尿病學會默沙東優秀論文獎
5. 2008 Peter Bennett’s Award, IDF/WPR Asia-Pacific Diabetes Epidemiology and
Education Training Course
6. 2008 Human Genome Organization (HUGO) Young Investigator Award
7. 2008 華夏內分泌學會年輕傑出研究獎
8. Top 10 Cited Paper (2010) Metabolism: Clinical and Experimental
9. 2013 中華民國糖尿病學會輝瑞優秀論文獎
10. 2014 中華民國糖尿病學會諾和諾德糖尿病傑出研究獎
11. 2016 臺大醫學院研究生優秀著作獎
12. 2016, 2020 年中華民國糖尿病學會研究計劃獎勵
13. 2016 跨世紀醫療促進基金會醫學研究獎
14. 2015,2017, 2018, 2021學年台灣大學學術研究績效獎勵
15. 2019 科技部未來科技突破獎 (台灣大學與國家衛生研究院團隊)
16. 2019臺灣醫學會雜誌年度最佳審查人獎
17. 臺大醫學院及臺大醫院兩院轉譯醫學2005, 2019, 2021,2022, 2023 獲獎團隊
18. 2024台灣大學資深優良教師
19. 2024中華民國糖尿病學會傑出研究獎
1. Academic Performance Award, National Taiwan University (1998)
2. Distinguished Academic Achievement Award of Residents, Department of Internal Medicine, National Taiwan University Hospital (2004)
3. Medical Research Award for Physicians in Working Professional Master’s Program, National Health Research Institutes, Taiwan (2006)
4. MSD Distinguished Research Paper Award, Diabetes Association of Taiwan (2007)
5. Peter Bennett’s Award, IDF/WPR Asia-Pacific Diabetes Epidemiology and Education Training Course (2008)
6. Young Investigator Award, Human Genome Organization (HUGO) (2008)
7. Young Investigator Award, 5th Huaxia Congress of Endocrinology (2008)
8. Top 10 Cited Paper of Metabolism (2010)
9. Pfizer Distinguished Research Paper Award, Diabetes Association of Taiwan (2013)
10. Novo Nordisk Distinguished Research Award, Diabetes Association of Taiwan (2014)
11. Outstanding Research Award for Graduate Students of National Taiwan University School of Medicine (2016)
12. Research Program Award of the Diabetes Society of the Republic of China (Taiwan) (2016, 2020)
13. Outstanding Research Award of the New Century Health Care Promotion Foundation (2016)
14. Academic Research Performance Award, National Taiwan University (2015, 2017, 2018, 2021)
15. Future Technology Breakthrough Award, Ministry of Science and Technology, Taiwan (2019)
16. Best Reviewer Award, Journal of Formosan Medical Association 2019
17. Translational Research Award of National Taiwan University Medical College and National Taiwan University (2018.2019, 2021, 2022, 2023)
18. Senior Excellent Teacher Award, National Taiwan University (2024)
19. Distinguished Research Award, Diabetes Association of Taiwan (2024)