曾慶平 教授
曾 慶 平 (CHING-PING TSENG) |
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學歷 |
美國威斯康辛麥迪遜分校人類腫瘤生物學博士 |
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任課科目 |
臨床血液學、臨床血液學實驗、臨床血液學實習、高等生物技術學、現代生物技術及分子診斷實驗 |
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研究專長 |
血小板生物學、轉譯癌症醫學、分子檢驗技術學、血液學 |
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辦公室分機 |
5202 |
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研究室分機 |
5216 |
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實驗室名稱 |
轉譯癌症暨血小板生物學研究室 |
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個人網頁 |
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研究方向及研究室特色(Lab & Research Interest) |
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本研究室主要探討血小板活化的機制及血小板在癌症轉移及血栓形成所扮演的角色;我們也開發癌症檢測的平台,建立循環腫瘤細胞的檢驗方法並探討循環腫瘤細胞的分子與細胞特性,將基礎研究的成果轉為臨床檢驗的平台。以下為本研究室主要的研究方向:
探討血小板活化的機制及血小板在癌症轉移與血栓形成所扮演的角色 血小板自 100 年前首次在文獻中被描述為「血液中的灰塵 (dust of the blood)」以來,一直被認為在止血及血栓形成的過程中扮演重要的角色。血小板的性質相當獨特。它是最小的一種血球,但卻是由骨髓中最大的巨核細胞 (megakaryocyte) 進行細胞質裂解而成。一個巨核細胞的細胞質先形成絲狀的前驅血小板 (pro-platelet),然後再裂解成 4000-5000 個血小板。近年的研究顯示血小板功能的多樣性,除了與心肌梗塞、缺血性中風、肺栓塞、骨髓增生性疾病 (myeloproliferative disease)、及其他血栓或心血管疾病的發生有關外,也與癌症的轉移、血液循環腫瘤細胞 (circulating tumor cells) 的存活、幹細胞的分裂與分化、免疫、及微生物感染等皆息息相關。基於血小板的獨特性質及與多種疾病的關聯性,多年來我們與不同的研究團隊合作,針對血小板在止血、血栓形成及癌症轉移的機轉上做深入的研究,藉此提供心血管疾病及癌症的預防與治療上新的發展方向。主要的研究方向為: (1) 探討血小板蛋白 Disabled-2 (Dab2) 表現及磷酸化對血小板活化及血栓形成的影響。 (2) 探討癌細胞表面蛋白 podoplanin (PDPN) 與 血小板蛋白 C–type lectin-like receptor 2 (CLEC-2) 交互作用在癌症轉移上的生理病理功能。 (3) 以 PDPN-CLEC-2 交互作用為作用標的,開發抑制癌細胞轉移的新醫材。
深入瞭解:
(1) 曾慶平。血小板的奧妙與研究點滴。長庚校訊105年 第147期。 (2) Tsai HJ, Cheng JC, Kao ML, Chiu HP, Chiang YH, Chen DP, Rau KM, Liao HR, Tseng CP. Integrin αIIbβ3 outside-in signaling activates human platelets through serine 24 phosphorylation of Disabled-2. Cell Biosci. 2021 Feb 8;11(1):32. (3) Lee HY, Yu NY, Lee SH, Tsai HJ, Wu CC, Cheng JC, Chen DP, Wang YR, Tseng CP. Podoplanin promotes cancer-associated thrombosis and contributes to the unfavorable overall survival in an ectopic xenograft mouse model of oral cancer. Biomed J. 2020. Apr;43(2):146-162. (4) Tseng CP , Huang YL, Chang YW, Liao HR, Chen YL, Hsieh PW. Polysaccharide-containing fraction from Artemisia argyi inhibits tumor cell-induced platelet aggregation by blocking interaction of podoplanin with C-type lectin-like receptor 2. J Food Drug Anal. Jan;28(1):115-123. 2020. (5) Tsai HJ, Chien KY, Liao HR, Shih MS, Lin YC, Chang YW, Cheng JC, Tseng CP. Functional links between Disabled-2 Ser723 phosphorylation and thrombin signaling in human platelets. J Thromb Haemost. 2017 Oct;15(10):2029-2044. (6) Tsai HJ, Tseng CP. The adaptor protein Disabled-2: new insights into platelet biology and integrin signaling. Thromb J. 2016 Oct 4;14(Suppl 1):28. (7) Tsai HJ, Huang CL, Chang YW, Huang DY, Lin CC, Cooper JA, Cheng JC, Tseng CP. Disabled-2 is required for efficient hemostasis and platelet activation by thrombin in mice. Arterioscler Thromb Vasc Biol. 2014 Nov;34(11):2404-12. (8) Chang YW, Hsieh PW, Chang YT, Lu MH, Huang TF, Chong KY, Liao HR, Cheng JC, Tseng CP. Identification of a novel platelet antagonist that binds to CLEC-2 and suppresses podoplanin-induced platelet aggregation and cancer metastasis. Oncotarget. 2015 Dec 15;6(40):42733-48.
循環腫瘤細胞檢測平台之開發及其分子特性的探討 癌症已連續多年位居國人十大死因之首位。癌細胞在身體內會藉由循環系統的攜帶,隨著血液的流動而增加癌細胞遠端轉移到其他器官的機會。這些細胞稱為循環腫瘤細胞 (circulating tumor cells, CTCs)。循環腫瘤細胞的數量及特性已經知道可以做為臨床藥物效率評估及癌症標靶藥物使用的參考。循環腫瘤細胞檢測是採用液態活檢 (liquid biopsy),為一種非侵入式的血液檢測,近年已成為癌症檢測的一大趨勢。然而,循環腫瘤細胞檢測所面臨的最大挑戰是從五十億到一百億個週邊血液細胞分離出極為罕見的循環腫瘤細胞。 我們研究室建立了一個負向篩選 (negative selection) 的檢測平台以分離與純化循環腫瘤細胞,提供轉譯癌症醫學在臨床應用與基礎研究一個簡便的循環腫瘤細胞偵測系統。此技術平台可有效降低紅血球與白血球殘留率,提高分離出腫瘤細胞的純度。所分離出來之有核細胞可進行全基因定序、特定基因突變偵測等檢測,有利於醫師判斷用藥方向。該技術平台並獲得科技部創新創業激勵計畫創業潛力獎。除了臨床應用平台的建立外,我們的研究也著重在探討循環腫瘤細胞的分子與細胞特性,以瞭解癌症轉移的病理基礎。
深入瞭解:
(1) Tsai WS, Hung WS, Wang TM, Liu H, Yang CY, Wu SM, Hsu HL, Hsiao YC, Tsai HJ, Tseng CP. Circulating tumor cell enumeration for improved screening and disease detection of patients with colorectal cancer. Biomed J.2021. (2) Rau KM, Liu CT, Hsiao YC, Hsiao KY, Wang TM, Hung WS, Su YL, Liu WC, Wang CH, Hsu HL, Chuang PH, Cheng JC, Tseng CP. Sequential circulating tumor cell counts in patients with locally advanced or metastatic hepatocellular carcinoma: monitoring the treatment response. J Clin Med. Jan 10;9(1). pii: E188. 2020. (3) Lin JD, Liou MJ, Hsu HL, Leong KK, Chen YT, Wang YR, Hung WS, Lee HY, Tsai HJ, Tseng CP. Circulating epithelial cell characterization and correlation with remission and survival in patients with thyroid cancer. Thyroid. 2018 Nov;28(11):1479-1489. (4) Tseng CP, Leong KK, Liou MJ, Hsu HL, Lin HC, Chen YA, Lin JD. Circulating epithelial cell counts for monitoring the therapeutic outcome of patients with papillary thyroid carcinoma. Oncotarget. 2017 Aug 24;8(44):77453-77464. (5) Lin HC, Liou MJ, Hsu HL, Hsieh JC, Chen YA, Tseng CP, Lin JD. Combined analysis of circulating epithelial cells and serum thyroglobulin for distinguishing disease status of the patients with papillary thyroid carcinoma. Oncotarget. 2016 Mar 29;7(13):17242-53. (6) Hsieh JC, Lin HC, Huang CY, Hsu HL, Wu TM, Lee CL, Chen MC, Wang HM, Tseng CP. Prognostic value of circulating tumor cells with podoplanin expression in patients with locally advanced or metastatic head and neck squamous cell carcinoma. Head Neck. 2015 Oct;37(10):1448-55. (7) Lin HC, Hsu HC, Hsieh CH, Wang HM, Huang CY, Wu MH, Tseng CP. A negative selection system PowerMag for effective leukocyte depletion and enhanced detection of EpCAM positive and negative circulating tumor cells. Clin Chim Acta. 2013 Apr 18;419:77-84.
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論文與著作(Publication) |
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代表性學術論文 (共 126 篇): 1. Chen DP, Tseng C-P (Co-first author), Wang WT, Sun CF. Genetic and mechanistic evaluation for the mixed-field agglutination in B3 blood type with IVS3+5G>A ABO gene mutation. PLoS One 7:e37272, 2012. (SCI) 2. Hung WS, Huang CL, Fan JT, Huang DY, Yeh CF, Cheng JC, Tseng C-P (Corresponding author). The endocytic adaptor protein Disabled-2 is required for cellular uptake of fibrinogen. Biochim Biophys Acta. 1823:1778-1788, 2012. (SCI) 3. Lee TH, Wu TS, Tseng C-P (Co-corresponding author), Qiu JT. High-resolution melting molecular signatures for rapid identification of human papillomavirus genotypes. PLoS One, 7:e42051, 2012. (SCI) 4. Huang SB, Wu MH, Lin YH, Hsieh CH, Yang CL, Lin HC, Tseng C-P (Co-corresponding author), Lee GB. High-purity and label-free isolation of circulating tumor cells (CTCs) in a microfluidic platform by using optically-induced-dielectrophoretic (ODEP) force. Lab Chip, 13:1371-83, 2013. (SCI) 5. Huang JT, Tseng C-P, Liao MH, Lu SC, Yeh WZ, Sakamoto N, Chen CM, Cheng JC. Hepatitis C virus replication is modulated by the interaction of non-structural protein NS5B and fatty acid synthase. J Virol. 87:4994-5004, 2013. (SCI) 6. Lin HC, Hsu HC, Hsieh CH, Wang HM, Huang CY, Wu MH, Tseng C-P (Corresponding author). A negative selection system PowerMag for effective leukocyte depletion and enhanced detection of EpCAM positive and negative circulating tumor cells. Clin Chim Acta. 419C:77-84, 2013. (SCI) 7. Chang SS, Hsieh WH, Liu TS, Lee SH, Wang CH, Chou HC, Yeo YH, Tseng C-P (Co-corresponding author), Lee CC. Multiplex PCR system for rapid detection of pathogens in patients with presumed sepsis - a systemic review and meta-analysis. PLoS One. 8:e62323, 2013. (SCI) 8. Chu HC, Lee HY, Huang YS, Tseng WL, Yen CJ, Cheng JC, Tseng C-P (Corresponding author). Erythroid differentiation is augmented in Reelin-deficient K562 cells and homozygous reeler mice. FEBS Lett. 588:58-64, 2014. (SCI) 9. Chen DP, Sun CF, Ning HC, Peng CT, Wang WT, Tseng C-P (Corresponding author). Real-time amplification of glyceraldehyde-3-phosphate dehydrogenase gene for quality control of leukopoor platelets. Transfusion. 54:445-50, 2014. (SCI) 10. Chu HC, Tseng WL, Lee HY, Cheng JC, Chang SS, Yung BY, Tseng C-P (Corresponding author). Distinct effects of Disabled-2 on transferrin uptake in different cell types and culture conditions. Cell Biol Int. 38:1252-1259, 2014. (SCI) 11. Tsai HJ, Huang CL, Chang YW, Huang DY, Lin CC, Cooper JA, Cheng JC, Tseng C-P (Corresponding author). Disabled-2 is required for efficient haemostasis and platelet activation by thrombin in mice. Arterioscler Thromb Vasc Biol 34:2404-2412, 2014. (SCI) 12. Tseng WL, Chen TH, Huang CC, Huang YH, Yeh CF, Tsai HJ, Lee HY, Kao CY, Lin SW, Liao HR, Cheng JC, Tseng C-P (Corresponding author). Impaired thrombin generation in Reelin-deficient mice: a potential role of plasma Reelin in hemostasis. J Thromb Haemost. 12:2054-2064, 2014. (SCI) 13. Chen DP, Sun CF, Ning HC, Peng CT, Wang WT, Tseng C-P (Corresponding author). Genetic and mechanistic evaluation for the weak A phenotype in Ael blood type with IVS6 + 5G>A ABO gene mutation. Vox Sang. 108:64-71, 2015. (SCI) 14. Hsieh CH, Lin HC, Huang CY, Hsu HL, Wu MH, Lee CL, Chen MC, Wang HM, Tseng C-P (Corresponding author). Prognostic value of circulating tumor cells with podoplanin expression in patients with locally advanced or metastatic head and neck squamous cell carcinoma. Head Neck 37:1448-1455, 2015. (SCI) 15. Chang YW, Hsieh PW, Chang YT, Lu MH, Huang TF, Chong KY, Liao HR, Cheng JC, Tseng C-P (Corresponding author). Identification of a novel platelet antagonist that binds to CLEC-2 and suppresses podoplanin-induced platelet aggregation and cancer metastasis. Oncotarget 6:42733-42748, 2015. (SCI) 16. Chen DP, Tseng C-P, Lin CJ, Wang WT, Sun CF. Mechanistic evaluation for mixed-field agglutination in the K562 cell study model with exon 3 deletion of A1 gene. Ann Clin Lab Sci. 45:674-679, 2015. (SCI) 17. Lin HC, Liou MJ, Hsu HL, Hsieh CH, Chen YA, Tseng C-P (Corresponding author), Lin JD. Combined analysis of circulating epithelial cells and serum thyroglobulin for distinguishing disease status of the patients with papillary thyroid carcinoma. Oncotarget 7: 17242-17253, 2016. (SCI) 18. Hsieh CH, Lin HC, Huang SB, Hsueh C, Hsu HL, Wang HM, Wu MH, Tseng C-P (Corresponding author), Lin JD. Circulating epithelial cell enumeration facilitates the identification and follow-up of a patient with early stage papillary thyroid microcarcinoma: A case report. Clin Chim Acta. 454:107-111, 2016. (SCI) 19. Chen DP, Sun CF, Ning HC, Wang WT, Tseng C-P (Corresponding author). Comprehensive analysis of RHD splicing transcripts reveals the molecular basis for the weak anti-D reactivity of Del -red blood cells. Transfus Med. 26:123-129, 2016. (SCI) 20. Hung WS, Ling P, Cheng JC, Chang SS, Tseng C-P (Corresponding author). Disabled-2 is a negative immune regulator of lipopolysaccharide-stimulated Toll-like receptor 4 internalization and signaling. Sci Rep. 6:35343, 2016. (SCI) 21. Chen DP, Chang SW, Jaing TH, Tseng C-P, Chen SH, Wang WT. Effect of HLA mismatching at HLA-A, -B, and -DRB1 for umbilical-cord blood transplantation in Taiwan. Clin Chim Acta. 462:162-165, 2016. (SCI) 22. Tsai HJ, Tseng C-P (Corresponding author). The adaptor protein Disabled-2: new insights into platelet biology and integrin signaling. Thromb J. 14(Suppl 1):28, 2016. Review 23. Cheng JC, Tseng C-P (Co-first author), Liao MH, Peng CY, Yu JS, Chuang PH, Huang JT, Chen JJW. Activation of hepatic stellate cells by the ubiquitin C-terminal hydrolase 1 protein secreted from hepatitis C virus-infected hepatocytes. Sci Rep. 7:4448, 2017. (SCI) 24. Tsai HJ, Chien KY, Liao HR, Shih MS, Lin YC, Chang YW, Cheng JC, Tseng C-P (Corresponding author). Functional links between Disabled-2 Ser723 phosphorylation and thrombin signaling in human platelets. J Thromb Haemost. 15:2029-2044, 2017. (SCI) 25. Chen DP, Wen YH, Lu JJ, Tseng C-P, Chen WL, Chang SW. Human platelet antigens are associated with febrile non-hemolytic transfusion reactions. Clin Chim Acta. 474:120-123, 2017. (SCI) 26. Tseng C-P (Corresponding author), Leong KK, Liou MJ, Hsu HL, Lin HC, Chen YA, Lin JD. Circulating epithelial cell counts for monitoring the therapeutic outcome of patients with papillary thyroid carcinoma. Oncotarget. 8:77453-77464, 2017. (SCI) 27. Li YR, Tseng C-P (Co-first author), Hsu HL, Lin HC, Chen YA, Chen ST, Liou MJ, Lin JD. Circulating epithelial cells as potential biomarkers for detection of recurrence in patients of papillary thyroid carcinoma with positive serum anti-thyroglobulin antibody. Clin Chim Acta. 477:74-80, 2018. (SCI) 28. Chang YW, Tseng CP (Co-first autor), Lee CH, Hwang TL, Chen YL, Su MT, Chong KY, Lan YW, Wu CC, Chen KJ, Lu FH, Liao HR, Hsueh C, Hsieh PW. β-Nitrostyrene derivatives attenuate LPS-mediated acute lung injury via the inhibition of neutrophil-platelet interactions and NET release. Am J Physiol Lung Cell Mol Physiol. 314:L654-L669, 2018. (SCI) 29. Chen DP, Wen YH, Lu JJ, Tseng C-P, Wang WT. Rapid rare ABO blood typing using a single PCR based on a multiplex SNaPshot reaction. J Formos Med Assoc. 2018. (SCI) 30. Chen DP, Chang SW, Jaing TH, Wang WT, Hus FP, Tseng C-P (Corresponding author). Single nucleotide polymorphisms within HLA region are associated with disease relapse for patients with unrelated cord blood transplantation. Peer J. 6:e5228, 2018. (SCI) 31. Lin JD, Liou MJ, Hsu HL, Leong KK, Chen YT, Wang YR, Hung WS, Lee HY, Tsai HJ, Tseng C-P (Corresponding author). Circulating epithelial cell characterization and correlation with remission and survival in patients with thyroid cancer. Thyroid. 28:1479-1489, 2018. (SCI) 32. Chen DP, Chang SW, Wang PN, Hus FP, Tseng C-P (Corresponding author). Association between single nucleotide polymorphisms within HLA region and disease relapse for patients with hematopoietic stem cell transplantation. Sci Rep. Sep 24;9(1):13731. 2019. (SCI) 33. Watanabe N, Kidokoro M, Suzuki Y, Tanaka M, Inoue S, Tsukamoto H, Hirayama N, Hsieh PW, Tseng CP, Nakagawa Y, Inokuchi S. A pull-down and slot blot-based screening system for inhibitor compounds of the podoplanin-CLEC-2 interaction. PLoS One. Sep 25;14(9):e0222331. 2019. (SCI) 34. Tseng C-P (Co-first author), Huang YL, Chang YW, Liao HR, Chen YL, Hsieh PW. Polysaccharide-containing fraction from Artemisia argyi inhibits tumor cell-induced platelet aggregation by blocking interaction of podoplanin with C-type lectin-like receptor 2. J Food Drug Anal. Jan;28(1):115-123. 2020. (SCI) 35. Rau KM, Liu CT, Hsiao YC, Hsiao KY, Wang TM, Hung WS, Su YL, Liu WC, Wang CH, Hsu HL, Chuang PH, Cheng JC, Tseng C-P (Corresponding author). Sequential circulating tumor cell counts in patients with locally advanced or metastatic hepatocellular carcinoma: monitoring the treatment response. J Clin Med. Jan 10;9(1). pii: E188. 2020. (SCI)
36 Lee HY, Yu NY, Lee SH, Tsai HJ, Wu CC, Cheng JC, Chen DP, Wang YR, Tseng C-P (Corresponding author). Podoplanin promotes cancer-associated thrombosis and contributes to the unfavorable overall survival in an ectopic xenograft mouse model of oral cancer. Biomed J. Apr;43(2):146-162. 2020. (SCI) 37. Tsai HJ, Cheng JC, Kao ML, Chiu HP, Chiang YH, Chen DP, Rau KM, Liao HR, Tseng C-P (Corresponding author). Integrin αIIbβ3 outside-in signaling activates human platelets through serine 24 phosphorylation of Disabled-2. Cell Biosci. Feb 8;11(1):32. 2021. (SCI) 38. Tsai WS, Hung WS, Wang TM, Liu H, Yang CY, Wu SM, Hsu HL, Hsiao YC, Tsai HJ, Tseng C-P (Corresponding author). Circulating tumor cell enumeration for improved screening and disease detection of patients with colorectal cancer. Biomed J.2021. (SCI)
專利: 1. 曾慶平、謝珮文、張耀文。一種含有5-硝基苯之衍生物,透過抑制腫瘤細胞誘發血小板凝集反應作為癌症轉移治療方式。中華民國專利 I444358。 2. 曾慶平、謝珮文、張耀文。Composition of 5-nitrobenzoate derivatives as anti-metastatic agent that inhibits tumor cell-induced platelet aggregation. 美國專利9956191。 3. 曾慶平、謝珮文、張耀文。Composition of 5-nitrobenzoate derivatives as anti-metastatic agent that inhibits tumor cell-induced platelet aggregation. 美國專利9604910。 4. 謝珮文、曾慶平、蔡昀真, 黃鈺凌、張耀文。Compounds, compositions and methods for treating tumors. 美國專利 10047039。 5. 張國友、曾慶平。氯硝柳氨及其衍生物的用途. 中華民國專利申請案I631944。 6. 張國友、曾慶平。Method of using niclosamide derivatives。美國專利申請案15/481455。 7. 曾慶平、張詩鑫。擴增與檢測目標微生物DNA的方法、組成與系統。中華民國專利I465572。 8. 曾慶平、張詩鑫。Methods, systems, and compositions for detection of microbial DNA by PCR. 美國專利 9388458。 9. 曾慶平、張詩鑫。Methods, systems, and compositions for detection of microbial DNA by PCR. 澳洲專利 AU-B-2012255042。 10. 曾慶平、張詩鑫。Methods, systems, and compositions for detection of microbial DNA by PCR. 蘇俄專利2620953。
11. 馬蘊華、曾慶平、鄭凱文(2019) 用以標的凝血因子XIII的適體及其用途。中華民國專利公開號202122581。 12 馬蘊華、曾慶平、鄭凱文(2019) 用以標的第十三凝血因子之核苷酸適體及其用途。美國專利申請。
專書: 1. 醫學分子檢驗 (五南出版社),2013 (初版) – 2018 (五版)。 第一章 分子檢驗基本技術(吳芳姿、王聖帆、許蕙玲、楊正芬、黃智生、鄭如茜、黃家群、曾慶平、孫光蕙 著) 第四章 高通量定序技術於分子檢驗之應用(邱全芊、駱紀東、黃家群、曾慶平 著) 第二十五章 癌症標靶藥物療效評估之分子檢測(曾慶平、邱全芊、黃家群、陳泰龍 著)
獲獎情形: 教師 (詳見研究室網頁): 1. 長庚大學優良教師教學獎, 2017. 2. 長庚大學優良教師研究獎, 2016. 3. 科技部創新創業激勵計畫創業潛力獎, 2014. 4. 台灣醫檢學會學術論文獎, 2011. 5. 長庚大學優良教師研究獎, 2008. 6. 台灣醫檢學會 Sysmex 論文獎, 2006. 7. 國際血栓暨止血學會 Reach The World 獎, 2005. 8. 台灣醫檢學會學術論文獎, 2003. 9. 國科會研究類甲種獎, 2001. 10.長庚大學優良教師輔導獎, 2000. 11. 台灣醫事檢驗學會108年度臨床應用組學術論文獎,2019 12. 開發之技術「IronMag循環腫瘤細胞自動化檢測系統」(已技轉至榮文生醫),獲頒「第17屆國家新創獎」企業新創組的生技製藥與精準醫療類獎項, 2021.
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科技部大專生計畫 1 林彥嘉. 研究題目:探討Disabled-2磷酸化與蛋白質交互作用的影響 (104學年度) 2 鄭雁如. 研究題目:PowerMag循環腫瘤細胞分離平台純化能力提升之探討 (105學年度) 3 李亞芸. 研究題目:Disabled-2的表現及其S723位點的磷酸化在口腔癌細胞所扮演的角色 (105學年度) 4 李婉琳. 研究題目:建立anti-Dab2 Ser394磷酸化之抗體並探討Dab2 Ser394磷酸化在細胞週期的影響 (108學年度) 5 黃薀宇. 研究題目:建立良好的血小板保存方式 (110學年度) 6 李柔臻. 研究題目:Podoplanin適體的應用與功能性技術之開發 (110學年度) |