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饒梓明 博士

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    資料來源：臨床醫學研究科       

    學術經歷：

    高雄榮民總醫院教學研究部 高級助理研究員 (2020/03迄今)

    國立臺灣大學毒理學研究所與臺大醫院內科部 博士後研究員 (2018/04至2020/02)

    日本東京大學慢性腎臟病病態生理學 特任助理教授 (2015/10至2018/03)

    國立臺灣大學醫學檢驗暨生物技術學系 博士後研究員 (2014/07至2015/09)

     

    學歷：

    博士 國立臺灣大學醫學檢驗暨生物技術學系 (2008/09月至2014/06)

    碩士 國立東華大學生物技術研究所 (1998/09月至2000/06)

    學士 淡江大學化學工程學系 (1993/09月至1998/06)

    Art editor Img

    論文著作獎：

    1. 科技部博士後研究人員學術著作獎 (2019)
    2. 臺大醫學檢驗暨生物技術學系系友學術著作獎，獲獎兩次 (2015、2017)

     

    出國研究/開會補助：

    1. 科技部補助從事國外博士後計畫 (千里馬計畫，2015-2016)
    2. 科技部補助出席國際會議，獲獎四次 (2011、2014、2015、2019)
    3. 教育部補助出席國際會議，獲獎二次 (2011、2012)

     

    論文口頭報告獎：

    1. 國際腎臟年會前10%摘要論文獎 (2018)
    2. 第六十屆日本腎臟年會，第一名 (2017)
    3. 第六屆日本慢性腎臟前導會議，傑出研究者獎 (2017)

     

    壁報論文獎：

    1. 第二十九屆生醫年會/臨床生化組，優秀壁報論文獎(2013)
    2. 第十屆台灣醫事檢驗年會，第一名 (2013)
    3. 第六屆亞太醫學檢驗科學國際研討會，優等獎 (2012)
    4. 第十七屆台灣癌症聯合學術年會，基轉組優等獎 (2012)
    5. 台灣基因醫學暨生物標記學會年會暨基因標記暨轉譯醫學應用研討會，第一名 (2012)
    1. 腎臟病與大腸直腸癌轉譯醫學
    2. 能量代謝與疾病
    3. 基因轉殖鼠應用

     

    Contribute to Science                                                                           

    1. Development of novel strategies for intervention of kidney diseases: My previous researches focused on lipotoxicity-induced kidney diseases. The lipid nephrotoxicity hypothesis was first outlined in 1982, however, the molecular mechanisms orchestrating this process are obscure. My study filled up this gap and identified a novel pathological factor, ATF6a, which deranges lipid metabolism of tubular cells and causes subsequent lipid nephrotoxicity in association with interstitial fibrosis via PPARa downregulation (Kidney International. 2019 Jan 10). In addition, we found that palmitate reduces erythropoietin (EPO) production via ATF4 activation and results in chronic kidney disease (CKD) (Kidney International. 2018 Jun 7). My researches also focused on identification of new uremic toxins. We unraveled D-serine as a novel uremic toxin, which exacerbates kidney senescence via GCN2 pathway, a mitochondria-mediated signaling (Scientific. Reports. 2017 Sep 11). My researches also revealed a novel pathway, cGAS-STING, which is activated by cisplatin-induced mitochondrial DNA leakage (Cell Reports. 2019 Oct 29). Thus, targeting lipotoxicity and new identified signaling pathways, including ATF6a-PPARa axis, ATF4, GCN2 and cGAS-STING, may provide alternative strategies for intervention of kidney diseases.

     

    1. Prevention of peritoneal fibrosis and calcification: Currently, my researches focus on discovering novel targets, which can be used for prevention of peritoneal calcification (PC). Frequently peritonitis or long-term peritoneal dialysis (PD) leads to PC. Peritonitis and long-term PD may elevate IL-6 expression in peritoneal cavity, which stimulates osteoblastic differentiation of human omental adipose-derived mesenchymal stem cells and results in PC development. Targeting IL-6 may be a promising therapeutic approach to preventing the progression of PC (Manuscript preparation, first author). My researches also focus on identifying predictive markers of peritoneal fibrosis (PF). We are now analyzing how many types of cells in peritoneal dialysis effluent (PDE) after PD and what pattern of transcriptomic landscape they are. We are delineating cell atlas of cells in PDEs by using single-cell RNA sequencing.

     

    1. Molecular cancer biology: My previous researches also focused on translational research of colorectal cancer (CRC). We, for the first time, identified PCDH10, SHISA3, NDST4 and CNTN4 as novel tumor suppressor genes (TSGs) on chromosome 4 in CRC and their downregulation predicted poor survival of patients with CRC (Annals of Surgical Oncology. 2015 Dec; 22 Suppl 3:S1481-9), (PLOS one 2013; 8(6): e67040). Ectopic PCDH10 suppresses tumor proliferation, migration, invasion in vitro, as well as tumorigenesis and liver metastasis in vivo (International Journal of Cancer. 2014; 135(11): 2593-2603). Applying transcriptomic approach combined with LC-MS/MS, we identified PCDH10-interacting protein, EGFR, in CRC cells. This is the first report revealing PCDH10-EGFR interaction (Cell Reports, submitted, first author). On the other hand, we established Ndst4 knockout mice and revealed its role in the differentiation of colonic epithelium. This is the first article reporting the physiological function of Ndst4 (Oncotarget. 2016 Dec 20; 7(51): 84938-84950).

     

    1. Virology: Despite tremendous efforts having been made to improve the methodology for constructing flavivirus cDNAs, the cause of toxicity of flavivirus cDNAs in bacteria remains unknown. We developed a novel strategy to construct dengue virus type 2 and Japanese encephalitis virus infectious clones using reverse genetic methodology. This report could be applied to other flaviviruses or pathogenic RNA viruses to facilitate research in virology, viral pathogenesis, and vaccine development (Journal of Virology 2011; 85: 2927-2941).

    1. 分子及細胞生物學：

    Molecular cloning, Lentivirus production, Stable clone generation

    2. 基因體學：

    RNA-seq, Single cell RNA-seq, Immunoprecipitation-mass spectrometry, GSEA analysis

    3. 小鼠疾病模式：

    Acute/chronic kidney disease, Subcutaneous/liver metastasis models of colorectal cancer

    Original articles

    1. Hiroshi Maekawa, Tsuyoshi Inoue, Tzu-Ming Jao, Reiko Inoue, Hiroshi Nishi, Rie Fujii, Fumiyoshi Ishidate, Tetsuhiro Tanaka, Yosuke Tanaka, Nobutaka Hirokawa, Masaomi Nangaku, Reiko Inagi. Mitochondrial DNA leakage causes inflammation via cGAS-STING signaling in cisplatin-induced acute kidney injury. Cell Reports. 2019 Oct 29;29(5):1261-1273.e6. (SCI, Rank 29/193, IF: 7.815)
    2. Tzu-Ming Jao, Masaomi Nangaku, Chia-Hsien Wu, Mai Sugahara, Hisako Saito, Hiroshi Maekawa, Mari Aoe, Yu Ishimoto, Tetsuhiro Tanaka, Bart Staels, Kazutoshi Mori and Reiko Inagi. ATF6a downregulation of PPARa promotes lipotoxicity-induced tubulointerstitial fibrosis. Kidney International. 2019 Jan 10. (SCI, Rank 5/80, IF: 8.306).
    3. Thitinun Anusornvongchai, Masaomi Nangaku, Tzu-Ming Jao, Chia-Hsien Wu, Yu Ishimoto, Hiroshi Maekawa, Tetsuhiro Tanaka, Akira Shimizu, Masayuki Yamamoto, Norio Suzuki, Ryoji Sassa and Reiko Inagi. Palmitate deranges erythropoietin production via ATF4 activation of unfolded protein response. Kidney International. 2018 Jun 7. (SCI, Rank 5/80, IF: 8.306).
    1. Akira Okada, Masaomi Nangaku, Tzu-Ming Jao, Hiroshi Maekawa, Yu Ishimono, Takahisa Kawakami and Reiko Inagi. D-serine, a novel uremic toxin, induces senescence in human renal tubular cells via GCN2 activation. Scientific. Reports. 2017 Sep 11. (SCI, Rank 15/69, IF: 4.011)
    2. Tzu-Ming Jao, Ya-Lin Li, Shu-Wha Lin, Sheng-Tai Tzeng, I-Shing Yu, Sou-Jhy Yen, Ming-Hong Tsai and Ya-Chien Yang. Alteration of colonic epithelial cell differentiation in mice deficient for glucosaminyl N-deacetylase/N-sulfotransferase 4. Oncotarget. 2016 Dec 20; 7(51): 84938-84950. (SCI, Rank 36/213, IF:5.008, at 2016).
    3. Ming-Hong Tsai, Wen-Chi Chen, Sung-Liang Yu, Chun-Chieh Chen, Tzu-Ming Jao, Chi-Yen Huang, Sheng-Tai Tzeng, Sou-Jhy Yen and Ya-Chien Yang. DNA hypermethylation of SHISA3 in colorectal cancer: An independent predictor of poor prognosis. Annals of Surgical Oncology. 2015 Dec; 22 Suppl 3:S1481-9. (SCI, Rank 27/203, IF: 3.681)
    4. Tzu-Ming Jao, Ming-Hong Tsai, Wei-Ting Weng, Hoi-Yan Lio, Chia-Yun Chang, Yen-Chun La and Ya-Chien Yang. Protocadherin 10 suppresses tumorigenesis and metastasis in colorectal cancer and its genetic loss predicts a poor prognosis. International Journal of Cancer. 2014; 135(11): 2593-2603. (SCI, Rank 51/229, IF: 4.982)
    5. Sheng-Tai Tzeng, Ming-Hong Tsai, Chi-Long Chen, Jing-Xing Lee, Tzu-Ming Jao, Sung-Liang Yu, Sou-Jhy Yen and Ya-Chien Yang. NDST4 is a novel candidate tumor suppressor gene at chromosome 4q26 and its genetic loss predicts adverse prognosis in colorectal cancer. PLOS one 2013; 8(6): e67040. (SCI, Rank 24/69, IF: 2.776)
    6. Szu-Yuan Pu, Ren-Huang Wu, Chi-Chen Yang, Tzu-Ming Jao, Ming-Han Tsai, Jing-Chyi Wang, Hui-Mei Lin, Yu-Sheng Chao and Andrew Yueh. Successful propagation of flavivirus infectious cDNAs by a novel method to reduce the cryptic bacterial promoter activity of virus genomes. Journal of Virology 2011; 85: 2927-2941. (SCI, Rank 8/36, IF: 4.324)

     

    Review articles

    1. Reiko Inagi, Yu Ishimoto and Tzu-Ming Jao. Foreseeing the future of glomerular disease through slits: miR-NPNT axis. Kidney International. 2017 Oct;92(4):782-784. (SCI, Rank 5/80, IF: 8.306).
    2. Yosuke Hirakawa, Tzu-Ming Jao and Reiko Inagi. Pathophysiology and therapeutics of premature ageing in chronic kidney disease, with a focus on glycative stress. Clin Exp Pharmacol Physiol. 2017 May 3. (SCI, Rank 154/267, IF: 2.336)

     

    1. Sho Hasegawa, Tzu-Ming Jao and Reiko Inagi. Dietary metabolites and chronic kidney disease. Nutrients. 2017 Apr 4;9(4). pii: E358. (SCI, Rank 16/86, IF: 4.171)
    2. Tzu-Ming Jao and Reiko Inagi. The gut-kidney connection in advanced chronic kidney disease. Health and Nutrition. 2016 Oct 1; (1): 17-28.

     

    International conference proceedings (in 5 years)

    Oral presentation

    1. Hiroshi Maekawa, Tzu-Ming Jao, Reiko Inoue, Hiroshi Nishi, Tsuyoshi Inoue, Masaomi Nangaku and Reiko Inagi. Mitochondrial DNA Leakage Causes Inflammation via the cGAS-STING Axis in Cisplatin-Mediated Tubular Damage. American Society of Nephrology Annual Meeting, 2018, Oct 23 – 28, San Diego, USA.
    2. Tzu-Ming Jao, Chia-Hsien Wu, Hiroshi Maekawa, Mari Aoe, Akira Okada, Yu Ishimoto, Masaomi Nangaku, Reiko Inagi. ATF6 and PPARa crosstalk provides a new insight in lipotoxicity-induced tubulointerstitial fibrosis. The 61th Annual Meeting of the Japanese Society of Nephrology, 2018, Jun 8 – Jun 10, Nigata, Japan.
    3. Tzu-Ming Jao, Chia-Hsien Wu, Hiroshi Maekawa, Mari Aoe, Yu Ishimoto, Masaomi Nangaku, Reiko Inagi. UPR deranges lipid metabolism and accelerates tubulointerstitial fibrosis: ATF6-PPARa axis. Japanese Society of Kidney and Lipids, 2018, Mar 17, Tokyo, Japan.
    4. Tzu-Ming Jao, Chia-Hsien Wu, Hiroshi Maekawa, Mari Aoe, Akira Okada, Yu Ishimoto, Masaomi Nangaku, Reiko Inagi. ATF6 activation drives lipotoxicity and tubulointerstitial fibrosis in renal ischemia-reperfusion injury. International Society of Nephrology Frontiers Meeting, 2018, Feb 22 – Feb 25, Tokyo, Japan.
    5. Tzu-Ming Jao, Chia-Hsien Wu, Hiroshi Maekawa, Mari Aoe, Yu Ishimoto, Masaomi Nangaku, Reiko Inagi. ATF6 Activation Drives Lipotoxicity and Tubulointerstitial Fibrosis in Mice with Ischemia-Reperfusion. The 8th Japan Society of Pathophysiology in Kidney Failure, 2017, Dec 9, Tokyo, Japan.
    6. Tzu-Ming Jao, Yu Ishimoto, Akira Okada, Hiroshi Maekawa, Masaomi Nangaku, Reiko Inagi. ATF6 deranges tubular homeostasis via mitochondrial fatty acid metabolism: a role for ATF6-PPARalpha axis. The 60th Annual Meeting of the Japanese Society of Nephrology, 2017, May 26-28, Sendai, Japan.

    Poster presentation

    1. Tzu-Ming Jao, Chia-Ter Chao, Chih-Kang Chiang, Shing-Hwa Liu, Jenq-Wen Huang, Kuan-Yu Hung. Targeting interleukin 6 and interleukin 8: a novel strategy for preventing the progression of peritoneal calcification. the 56th ERA-EDTA Congress, 2019, June 13-16, Budapest, Hungary.
    2. Tzu-Ming Jao, Chia-Hsien Wu, Hiroshi Maekawa, Mari Aoe, Akira Okada, Yu Ishimoto, Masaomi Nangaku, Reiko Inagi. ATF6 mediated lipotoxicity drives tubulointerstitial fibrosis in mice with ischemia-reperfusion injury. Asian Pacific Society of Nephrology, 2018, Mar 27 – Mar 31, Beijing, China.
    3. Tzu-Ming Jao, Chia-Hsien Wu, Mai Sugahara, Saito Hisako, Yu Ishimoto, Akira Okada, Hiroshi Maekawa, Mari Aoe, Tetsuhiro Tanaka, Masaomi Nangaku, Reiko Inagi. ATF6 knockout mice revealed that ER stress links lipotoxicity and kidney fibrosis. American Society of Nephrology Annual Meeting, 2017, Oct 31 – Nov 5, New Orleans, USA.
    4. Akira Okada, Tzu‑Ming Jao, Hiroshi Maekawa, Yu Ishimoto, Masaomi Nangaku and Reiko Inagi. D-Serine, a novel emerging uremic toxin candidate, induces cell cycle arrest and apoptosis through up-regulation of er stress and oxidative stress in proximal tubular cells. American Society of Nephrology Annual Meeting, 2016, Nov. 15-20, Chicago, USA.
    5. Tzu-Ming Jao, Ming-Hong Tsai, Wei-Ting Weng, Hoi-Yan Lio and Ya-Chien Yang. Protocadherin 10 suppresses tumorigenesis and metastasis via down-regulation of AKT/GSK3β and up-regulation of p53/p21 signaling pathways in colorectal cancer. 20th annual Taiwan Joint Cancer Conference, 2015, May 2-3, Taipei, Taiwan.
    6. Tzu-Ming Jao, Ming-Hong Tsai, Sheng-Tai Tzeng and Ya-Chien Yang. N-deacetylase/N-sulfotransferase (heparan glucosaminyl) 4, a novel tumor suppressor, suppresses tumorigenesis and liver metastasis of colorectal cancer cells in mice. AACR Annual Meeting, 2015, Apr 18-22, Philadelphia, Pennsylvania, USA.
    7. Yu-Lin Hung, Tzu-Ming Jao, Ming-Hong Tsai, Wei-Ting Weng and Ya-Chien Yang. Protocadherin 10-mediated suppression of tumorigenesis and metastasis in colorectal cancer. AACR Annual Meeting, 2015, Apr 18-22, Philadelphia, Pennsylvania, USA.
    8. Pi-Han Lin, Tzu-Ming Jao, Hsing-Pang Hsieh and Sui-Yuan-Chang. BPR2P001S0, a Coumarin derivative, induced cell cycle arrest in A549 through inhibiting PDPK1 activity. AACR Annual Meeting, 2015, Apr 18-22, Philadelphia, Pennsylvania, USA.

     

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