研究興趣
生物分子影像 (molecular imaging) 近年來已成為一新興的研究領域,藉由核醫藥物或報導基因等方式將活體內的生理生化反應,非侵入且即時反應活體內情形,藉此可了解不同細胞,如癌細胞與周遭腫瘤微環境的交互作用;抑或可用於評估藥物是否適用於病人,達到個人化的精準醫療,提高有效治療。
放射治療為目前癌症治療的主力之一,但對於具輻射抗性或已轉移之癌細胞效果不彰。因此,如何增進放射治療之療效為一重要課題。脂肪酸合成酶 (Fatty acid synthase, FASN) 為體內脂肪酸合成重要酵素,脂肪酸為重要生物分子,與細胞膜組成激素合成皆有密切關係。研究發現,與正常細胞不同,多數癌細胞大量表現FASN以供應足夠細胞組成原料及能量來源供癌細胞快速增生。然而,FASN表現是否影響細胞之輻射抗性仍未清楚,是否可藉調節FASN表現,達到增進放射治療效果亦尚須探討。
目前放射治療療效評估係利用CT或MRI判斷腫瘤體積是否變小,但單就體積變化並無法精確判斷治療效果,如腫瘤體積不變,但腫瘤內部凋亡或壞死時。此外核醫常用18F-FDG PET雖可利用癌細胞較正常細胞有更多的葡萄糖攝取之特性做為癌症偵測工具; 但當癌細胞及放射治療引起之發炎反應 (Radiation-induced inflammation) 並存時,18F-FDG影像便無法準確反映殘存的癌細胞與治療前之差異。因此若能發展一可反映放射治療療效之工具,將對放射治療的臨床應用有極大助益。
本實驗室主要研究興趣於探討調控FASN分子表現是否可增進放射治療效果,透過生物分子影像技術於動物體內追蹤放射治療後FASN 為主的基因轉殖細胞FASN表現的變化反之亦利用分子基因的方式使癌細胞表現不同量的FASN測試所形成之腫瘤,其輻射敏感度是否不同,此外,也將探討FASN 與其他分子表現的關係。此研究結果將有助於放射治療療效,並提供相關機制及新興療法之可能性。實驗室另一研究主題為,利用可被放射線活化基因為核心建立帶有報導基因之載體,選擇具專一性且可利用臨床常規檢查之報導基因,發展出可評估放射治療預後的分子診斷平台。
學術著作
期刊論文
- Chuang HY, Hori SS, Aalipour A, D’Souza AL, Gambhir SS. Ultrasensitive blood and urine-based cancer detection by self-replicating tumor-specific minicircles. (Manuscript in preparation)
- Chuang HY**, D’Souza AL, Gambhir SS. Cancer detection using an artificial secretable microRNA found in blood and urine. (Manuscript in preparation)
- Chuang HY, Lee YP, Lin WC, Hwang JJ. Fatty acid inhibition augments radiotherapy efficacy in androgen-dependent and –independent prostate cancer cell via NF-kB-mediated radiosensitization. (Manuscript in preparation)
- Aalipour A, Chuang HY, Murty S, D’Souza A, Park SM, Gulatid G, Gowrishankar G, Robinson ER, Zhiane Z, Gambhir SS. Engineered immune cells as highly sensitive diagnostic probes of disease. (Nature BME, under final review)
- Lee JR, Chan CT, Ruderman D, Chuang HY, Gaster RS, Atallah M, Mallick P, Lowe SW, Gambhir SS, Wang SX. (2017) Longitudinal monitoring of antibody responses against tumor cells using magneto-nanosensors with a nanoliter of blood. Nano Lett. DOI: 10.1021/acs.nanolett.7b02591
- Ronald JA, Kim BS, Gowrishankar G, Namavari M, Alam IS, D’Souza A, Nishikii H, Chuang HY, Ilovich O, Lin CF, Reeves R, Shuhendler A, Hoehne A, Chan CT, Baker J, Yaghoubi SS, VanBrocklin HF, Hawkins R, Franc BL, Jivan S, Slater JB, Verdin EF, Gao KT, Benjamin J, Negrin R, Gambhir SS. (2017) A PET imaging strategy to visualize activated T cells in acute graft-versus-host disease elicited by allogenic hematopoietic cell transplant. Cancer Res;77(11):2893-2902
- Chen JC, Chuang HY**, Hsu FT, Chen YC, Chien YC, Hwang JJ. (2016) Sorafenib pretreatment enhances radiotherapy through targeting MEK/ERK/NF-κB pathway in human hepatocellular carcinoma-bearing mouse model. Oncotarget;7(51):85450-85463
- Ronald JA, D’Souza AL, Chuang HY, Gambhir SS. (2016) Artificial microRNAs as novel secreted reporters for cell monitoring in living subjects. PLoS One;11(7):e0159369
- Shen YA, Wang CY, Chuang HY, Hwang JJ, Chi WH, Shu CH, Ho CY, Li WY, Chen YJ. (2016) CD44 and CD24 coordinate the reprogramming of nasopharyngeal carcinoma cells towards a cancer stem cell phenotype through STAT3 activation. Oncotarget;7(36):58351-58366
- Wang WH, Chuang HY**, Chen CH, Chen WK, Hwang JJ. (2016) Lupeol acetate ameliorates collagen-induced arthritis and osteoclastogenesis of mice through improvement of microenvironment. Biomed. Pharmacother;79:231-240
- Hsu FT, Chen TC, Chuang HY, Chang YF, Hwang JJ. (2015) Enhancement of adoptive T Cell transfer with single low dose pretreatment of doxorubicin or paclitaxel in mice. Oncotarget;6: 44134–44150
- Fang CK, Chuang HY**, Wang WH, Liu RS, Wang SJ, Hwang JJ. (2015) Chronic Effects of Cocaine on Dopaminergic and Serotonergic Systems of Rats. Current Molecular Imaging;4: 43-52
- Ronald JA, Chuang HY, Dragulescu-Andrasi A, Hori SS, Gambhir SS. (2015) Detecting cancers through tumor-activatable minicircles that lead to a detectable blood biomarker. PNAS;112:3068-3073
- Chuang HY**, Chang YF, Liu RS, Hwang JJ. (2014) Serial low doses of sorafenib enhance therapeutic efficacy of adoptive t cell therapy in a murine model by improving tumor microenvironment. PLoS ONE;9: e109992
- Fang CK, Chang YF, Chuang HY, Chen HW, Hwang JJ. (2014) Molecular imaging of neuropsychiatry and boron neutron capture therapy in neuro-oncology. Current Molecular Imaging;3:15-26
- Ronald JA, Cusso L, Chuang HY, Yan X, Dragulescu-Andrasi A, Gambhir SS. (2013) Development and validation of non-integrative, self-limited, and replicating minicircles for safe reporter gene imaging of cell-based therapies. PLoS ONE;8: e73138
- Chen HW, Chang YF, Chuang HY, Tai WT, Hwang JJ. (2012) Targeted therapy with fatty acid synthase inhibitors in a human prostate carcinoma LNCaP/tk-luc bearing animal model. Pros Cancer Pros Disease;15:260-264
- Chang YF, Chuang HY**, Hsu CH, Liu RS, Gambhir SS, Hwang JJ. (2012) Immunomodulation of curcumin on adoptive therapy with T cell functional imaging in mice. Cancer Prev Res;5:444-452
- Chuang HY**, Chang YF, Hwang JJ. (2011) Antitumor effect of orlistat, a fatty acid synthase inhibitor, is via activation of caspase-3 on human colorectal carcinoma-bearing animal. Biomed. Pharmacother;65:286-292
- Liu JH, Wann H, Chen MM, Pan WH, Chen YC, Liu CM, Yeh MY, Tsai SK, Young MS, Chuang HY, Chao FP, Chao HM. (2010) Baicalein significantly protects human retinal pigment epithelium cells against H₂O₂-induced oxidative stress by scavenging reactive oxygen species and downregulating the expression of matrix metalloproteinase-9 and vascular endothelial growth factor. J Ocul Pharmacol Ther;26:421-429
- Liu JH, Chen MM, Huang JW, Wann H, Ho LK, Pan WH, Chen YC, Liu CM, Yeh MY, Tsai SK, Young MS, Ho LT, Kuo CD, Chuang HY, Chao FP, Chao HM. (2010) Therapeutic effects and mechanisms of action of mannitol during H2O2-induced oxidative stress in human retinal pigment epithelium cells. J Ocul Pharmacol Ther;26(3):249-257
研討會論文
- Chuang HY and Hwang JJ. Combination effects of sorafenib with ionizing radiation on human oral carcinoma-bearing animal model. Oral presentation delivered at the World Molecular Imaging Congress, Honolulu, HI, USA, September 2015.
- Chuang HY and Hwang JJ. Immunomodulation effect of Sorafenib on Adoptive Cell Therapy In Vivo. Oral presentation delivered at the 10th Annual Meeting of the Japanese Society for Molecular Imaging conjunct with a FASMI annual meeting, Tokyo, Japan, May 2015.
- Chuang HY and Hwang JJ. Sorafenib increases numbers and functions of tumor-infiltrated T cells and enhances therapeutic outcomes of adoptive T cell therapy by modifying tumor microenvironment. Poster presentation delivered at the AACR Annual Meeting, San Diego, USA, April 2014.
- Ronald JA, Chuang HY, Franzini A, Hori SS, Gambhir SS. Tumor-specific minicircles as a novel safe technology for cancer screening via blood-based and molecular imaging assays. Poster presentation delivered at the World Molecular Imaging Congress, Savannah, GA, USA, September 2013.
- Chan CT, Shuhendler AJ, Chuang HY, Ye D, Sathirachinda A, Kotsuma M, Miething CC, Lowe S, Rao J, Gambhir SS. High Resolution Imaging of Apoptosis within a Murine Lymph Node and Spleen in Living Mice using A Novel self-assembling caspase-3 sensitive probe. Poster presentation delivered at the World Molecular Imaging Congress, Savannah, GA, USA, September 2013.
- Chuang HY, Chang YF, Hwang JJ. Immunomodulation Effect of Sorafenib on Adoptive Cell Therapy. Poster presentation delivered at the World Molecular Imaging Congress, Dublin, Ireland, September 2012.
- Chuang HY, Chang YF, Hsu CH, Hwang JJ. Therapeutic evaluation of cucumin combined with adoptive therapy in a tumor-bearing animal model via in vivo imaging of CD8+ T-cell function. Oral presentation delivered at the World Molecular Imaging Congress, San Diego, USA, September 2011.
- Hsu CH, Chang YF, Chuang HY, Wang WH, Hwang JJ. Granzyme B is a key factor responsible for rheumatoid arthritis in mice evaluated with molecular imaging. Poster presentation delivered at the World Molecular Imaging Congress, San Diego, USA, September 2011.
- Chuang HY, Chang YF, Shih NY, Hwang JJ. In vitro and in vivo characterization of novel ENO1-targeting monoclonal antibody for detection of breast cancer. Poster presentation delivered at the 13th Biennial Meeting of the International Gynecologic Cancer Society, Prague, Czech Republic, October 2010.
- Chuang HY, Liu RS, Hwang JJ. Therapeutic Evaluation in HT-29/tk-luc Tumor-bearing animal model with molecular imaging using fatty acid synthase inhibitor- orlistat. Poster presentation delivered at the World Molecular Imaging Congress, Montreal, Canada, September 2009.
- Chuang HY, Liu RS, Hwang JJ. Therapeutic evaluation in HT-29/tk-luc tumor-bearing animal model with molecular imaging using fatty acid synthase inhibitor- Orlistat. Poster presentation delivered at the SNM 56th Annual Meeting, San Antonio, USA, June 2009.
- Chuang HY and Hwang JJ. Therapeutic Evaluation in HT-29/tk-luc Tumor-Bearing Animal Model with Molecular Imaging Using Fatty Acid Synthase Inhibitor- Orlistat. Poster presentation delivered at the Annual Meeting of Taiwanese Society for Molecular Imaging, Taichung, Taiwan, November 2009.
- Chuang HY, Li CJ, Chang YF, Wang HE, Shih NY, Hwang JJ. Therapeutic evaluation of human breast carcinoma with immune-chemo-radiotherapy using enolase as a target. Poster presentation delivered ar the SNM 55th Annual Meeting, New Orleans, USA, June 2008.
- Chuang HY, Li CJ, Chang YF, Wang HE, Shih NY, Hwang JJ. Therapeutic evaluation of human breast carcinoma with immune-chemo-radiotherapy using enolase as a target. Oral presentation and poster presentation delivered at the Annual Meeting of Taiwanese Society for Molecular Imaging, Taipei, Taiwan, November 2007.
證照及證書
1. 醫事放射師 (放字)
2. 輻射防護專業測驗及格 (輻防師)
得獎及榮譽紀錄
1. 科技部補助赴國外博士後研究獎學金(2016-2017) 2. 斐陶斐榮譽學會 榮譽會員(06/2015) 3. Women in Molecular Imaging Scholar Award World Molecular Imaging Congress, Honolulu, USA(09/2015) 4. Young Investigator Award 10th Annual Meeting of the Japanese Society for Molecular Imaging conjunct with a FASMI annual Meeting, Tokyo, Japan(05/2015) 5. Student Travel Stipend Award World Molecular Imaging Congress(2011, 2012, 2015) 6. 科技部補助博士生赴國外研究獎學金(2013-2014)7. 教育部學海飛颺獎學金(2012-2013) |
聯絡方式
辦公室:研究大樓247室
電話:(02)2826-7241 (office)
電子信箱:huiyen@nycu.edu.tw