近年研究主題

  1. 以蛋白體學技術探討受異位表達ATP合成酶運送影響之磷酸化與乙醯化交互作用動態變化
  2. 以蛋白體學探討ATP合成酶如何透過胞外囊泡進行細胞與細胞間的溝通
  3. 以基因表現巨量數據尋找高危險群神經母細胞瘤之新穎組合治療策略
  4. 整合基因體編輯和多層體學方法探討長鏈非編碼核糖核酸SNHG1在高危險性神經母細胞瘤的分子功能

研究室簡介

系統生物學著重於以系統的觀點來了解生物系統的運作。由於高通量藥物合成、蛋白質體、微陣列、次世代定序及生物資訊技術的發展,使得系統生物學的研究愈發可行了。生物轉變的整體研究將能加快闡明生化路徑及疾病治療的速度。除此之外,系統生物學也著重於描述和了解複雜的生物系統如何運作以及發展預測人類疾病的模式。雖然疾病生物學很複雜,而藥物開發則必需倚靠生物反應,但是“基因到藥物”的希望之路已經是一觸即發,即將成功。本研究室也運用人工智慧(AI)技術進行藥物和基因表現的大數據分析,尋找老藥新用的新契機,並以細胞和動物實驗探究這些藥物新的作用機轉。

ATP 合成酶是細胞中重要的酵素,它能產生「能量貨幣分子」—ATP。Paul D. Boyer和John E. Walker因為釐清ATP合成的酵素機制而在1997年獲頒諾貝爾化學獎。長時間以來,ATP 合成酶一直被認為只出現在動物的粒線體內膜上,然而愈來愈多的證據顯示ATP 合成酶也會表現在癌組織的表皮細胞、乳癌和肺癌細胞,以及高危險性神經母細胞瘤的細胞膜上,這一類的ATP 合成酶被稱作「細胞膜異位表達ATP合成酶」。除了我們在2008年、2012年及2014年分別發表於Journal of Proteome Research、Cancer Research及Cell Death & Disease的文章中,證明阻斷細胞膜異位表達ATP合成酶的活性可以有效地抑制癌細胞生長外,也有許多報導指出細胞膜異位表達ATP合成酶具有可當作抗腫瘤及抑制血管新生藥物標靶的潛力。除此之外,我們發現它也出現在胞外囊泡膜上。細胞膜異位表達ATP合成酶是一個重要的蛋白質,但是它為何出現在細胞膜和胞外囊泡? 以及它在細胞膜及胞外囊泡的功能為何? 目前仍不是很清楚。因此本實驗室利用細胞和分子生物學、穿透式電子顯微鏡 (Cryo-EM),並結合體學技術(包括基因體、轉錄體、蛋白體和代謝體)和生物資訊學探討這些問題。

神經母細胞瘤(neuroblastoma;簡稱NB)是兒童最常見的頭外固態腫瘤,其中約20–25%帶有MYCN致癌基因放大現象。MYCN癌蛋白為Myc轉錄因子家族的一員,帶有MYCN基因放大的腫瘤屬於極高危險群,儘管經過多科整合治療,預後仍極為不佳。最近研究發現,某些長鏈非編碼核糖核酸(Long non-coding RNA,簡稱lncRNAs)在NB腫瘤生成與疾病惡化的過程中扮演重要角色。因此,若能深入探討MYCN與lncRNA間的調控網路,可更加了解NB的致病機轉,並有機會找到新的治療標靶。本實驗室目前的研究重點之一為探討神經母細胞瘤MYCN癌蛋白所驅動之lncRNA調控網路,並利用CRISPR/CAS9的基因體編輯技術將長鏈非編碼核糖核酸剃除,進而以多層體學方法探討它在高危險性神經母細胞瘤的分子功能。除此之外,我們也以基因表現巨量數據尋找高危險群神經母細胞瘤之新穎組合治療策略。

系統生物學研究室

Research

  1. Systems-biology study of a novel compound on cancer cells.
  2. Development of Open Bioinformatics Software to Uncover the Mechanism of TPA-induced Differentiation from Leukemia Cells to Macrophages.
  3. Elucidating the Molecular Regulation of Ganoderma lucidum Polysaccharides in Human Monocytic Cells : from Gene Expression to Network Construction.
  4. Applying the functional genomics of Rhodopseudomonas palustris to develop biomass energy technological platform

Laboratory

The main research in our lab is to integrate chemistry, biology and computation to investigate the molecular mechanism of apoptosis in drugs-induced cancer cells using systems biology approach; furthermore, to discover novel drugs for cancer therapy.

Systems biology is a new field in biology that focuses on understanding of functional activity from a systems-wide perspective. Recently, with the advent of high-throughput drug synthesis, proteomics, microarray and bioinformatics technologies, the study of systems biology has become possible. The holistic study of biological transformations will enable more rapid advances in elucidating biochemical pathways and disease therapies.The hope of the rapid translation of 'genes to drugs' has foundered on the reality that disease biology is complex, and that drug development must be driven by insights into biological responses. In my laboratory, we integrate chemistry, biology and computation to investigate the molecular mechanism of apoptosis in RGD-peptide-induced cancer cells using systems biology approach; furthermore, to discover novel drugs for cancer therapy.

In 2001, human genome sequence has been completed. However, the determination of the complete genome sequence is not the end of the story. Actually, it is the beginning of “post-genome informatics”. Both the public and private sectors are unprecedented amounts of resources in order to quickly decipher the genomes and to claim discovery of the information. We are joining the “wars”. In our study, we used HL-60, a human myeloid cancer cell line, which can be induced to differentiate into benign noncancerous macrophages by TPA. What are the interactions between proteins during this differentiation is very important in investigating cellular mechanism. In our previous study, we used two high-throughput technologies-proteomics and cDNA microarray to detect the expression of proteins and genes, respectively (has been published in Electrophoresis, 2002). In this research, we try to investigate how the cellular mechanism to control this differentiation process.

Rhodopseudomonas palustris(R. palustris)is a purple nonsulfur anoxygenic phototrophic bacterium that belongs to the a-proteobacteria. It is a common soil and water bacterium that makes its living by converting sunlight to cellular energy and by absorbing atmospheric carbon dioxide and converting to biomass. Biomass can be burned directly for thermal energy or converted to other high-value energy sources including ethanol, biodiesel, methanol, hydrogen, or methane. The advantage of R. palustris is that it can obtain the energy necessary for hydrogen production through photosynthesis driven by the “free” supply of sunlight. In this research, we would like to elucidate the functional genome of R. palustris using systems biology approach; then apply the results to develop biomass energy technological platform.

Systems Biology Lab.


代表著作

Publications

期刊論文 Journal
  1. Lee, W.-H., Chen, K.-P., Wang, K., Huang, H.-C.*, Juan, H.-F.* (2019) “Characterizing the cancer-associated microbiome with small RNA sequencing data” Biochemical and Biophysical Research Communications (In press).
  2. Chang, H.-C., Huang, H.-C., Juan, H.-F.*, Hsu, C.-L* (2019) “Investigating the role of super-enhancer RNAs underlying embryonic stem cell differentiation” BMC Genomics (In press).
  3. Hsieh, C.-H., Cheung, C. H. Y., Liu, Y.-L., Hou, C.-L., Hsu, C.-L., Huang, C.-T., Yang, T.-S., Chen, S.-F., Chen, C.-N., Hsu, W.-M.*, Huang, H.-C.*, Juan, H.-F.* (2019) “Quantitative proteomics of Th-MYCN transgenic mice reveals aurora kinase inhibitor altered metabolic pathways and enhanced ACADM to suppress neuroblastoma progression” Journal of Proteome Research 18(11):3850-3866.
  4. Cheung, H. Y. C., Hsu, C.-L., Tsuei, C.-Y., Kuo, T.-T., Huang, C.-T., Hsu, W.-M., Chung, Y.-H., Wu, H.-Y., Hsu, C.-C., Huang, H.-C.*, Juan, H.-F.* (2019) “Combinatorial targeting of MTHFD2 and PAICS in purine synthesis as a novel therapeutic strategy” Cell Death & Disease 10:786.
  5. Wu, P.-Y., Yu, I-S., Lin, Y.-C., Chang, Y.-T., Chen, C.-C., Lin, K.-H., Tseng, T.-H., Kargren, M., Tai, Y.-L., Shen, T.-L., Liu, Y.-L., Wang, B.-J., Chang, C.-H., Chen, W.-M., Juan, H.-F., Huang, S.-F., Chan, Y.-Y., Liao, Y.-F., Hsu, W.-M., Lee, H. (2019) “Activation of aryl hydrocarbon receptor by kynurenine impairs progression and metastasis of neuroblastoma” Cancer Research 79(21):5550-5562.
  6. Huang, C.-T., Hsieh, C.-H., Lee, W.-C., Liu, Y.-L., Yang, T.-S., Hsu, W.-M., Oyang, Y.-J., Huang, H.-C.*, Juan, H.-F.* (2019) “Therapeutic targeting of non-oncogene dependencies in high-risk neuroblastoma” Clinical Cancer Research 25(13):4063-4078.
  7. Yang, T.-W., Sahu, D., Chang, Y.-W., Hsu, C.-L., Hsieh, C.-H., Huang, H.-C.*, Juan, H.-F.* (2019) “RNA-binding proteomics reveals MATR3 interacting with lncRNA SNHG1 to enhance neuroblastoma progression” Journal of Proteome Research 18: 406–416.
  8. Chang, J.-Y., Yu, W.-H., Juan, H.-F.*, Huang, H.-C.* (2018) “Dynamics of alternative polyadenylation in human preimplantation embryos” Biochemical and Biophysical Research Sep 11. pii: S0006-291X(18)31946-6.
  9. Huang, C.-T., Hsieh, C.-H., Oyang, Y.-J., Huang, H.-C.*, Juan, H.-F.* (2018) "A large-scale gene expression intensity-based similarity metric for drug repositioning" iScience 7: 40-52. (Cell Press)
  10. Lin, M.-C., Chien, P.-H., Wu, H.-Y., Chen, S.-T., Juan, H.-F., Lou, P.-J.*, Huang, M.-C.* (2018) "C1GALT1 predicts poor prognosis and is a potential therapeutic target in head and neck cancer" Oncogene Jun 21. doi: 10.1038/s41388-018-0375-0
  11. Sahu, D., Ho, S.-Y., Juan, H.-F.*, Huang, H.-C.* (2018) "High-risk, expression-based prognostic long noncoding RNA signature in neuroblastoma" JNCI Cancer Spectrum 2(2): pky015.
  12. Cheng, A.-N., Fan, C.-C., Lo, Y.-K., Kuo, C.-L., Wang, H.-C., Lien, I-H., Lin, S.-Y., Chen, C.-H., Jiang, S. S., Chang, I-S., Juan, H.-F., Lyu, P.-C., Lee, A Y.-L.* (2017) "Cdc7-Dbf4-mediated phosphorylation of HSP90-S164 stabilizes HSP90-HCLK2-MRN complex to enhance ATR/ATM signaling that overcomes replication stress in cancer" Scientific Reports 7: 17024.
  13. Cheung, H. Y. C., Hsu, C.-L., Chen, K.-P., Chong, S.-T., Huang, H.-C.*, Juan, H.-F.* (2017) "MCM2-regulated functional networks in lung cancer by multi-dimensional proteomic approach" Scientific Reports 7(1):13302.
  14. Hsu, C.-L., Wang, J.-K., Lu, P.-C., Huang, H.-C.*, and Juan, H.-F.* (2017) "DynaPho: a web platform for inferring the dynamics of time-series phosphoproteomics" Bioinformatics 33(22):3664-3666.
  15. Hua, K.-T., Liu, Y.-F., Hsu, C.-L., Cheng, T.-Y., Yang, C.-Y., Chang, J.-S., Lee, W.-J., Hsiao, M., Juan, H.-F., Chien, M.-H.*, Yang, S.-F.* (2017) "3'UTR polymorphisms of carbonic anhydrase IX determine the miR-34a targeting efficiency and prognosis of hepatocellular carcinoma" Scientific Reports 7:4466.
  16. Cheung, C. H.-Y., Juan, H.-F.*. (2017) "Quantitative Proteomics in Lung Cancer" Journal of Biomedical Science 24:37.
  17. Liao, S.-Y., Chiang, C.-W., Hsu, C.-H., Jen, J., Juan, H.-F., Lai, W.-W., and Wang, Y.-C.* (2017) "CK1δ/GSK3β/FBXW7α axis promotes degradation of the ZNF322A oncoprotein to suppress lung cancer progression" Oncogene 36(41):5722-5733.
  18. Lin, T-.C., Chen, S.-T., Huang, M.-C., Huang, J., Hsu, C.-L., Juan, H.-F., Lin, H.-H., Chen, C.-H.* (2017) "GALNT6 expression enhances aggressive phenotypes of ovarian cancer cells by regulating EGFR activity" Oncotarget 8(26):42588-42601.
  19. Lin, M.-C., Lin, J.-J., Hsu, C.-L., Juan, H.-F., Lou, P.-J.*, Huang, M.-C.* (2017) "GATA3 interacts with and stabilizes HIF-1α to enhance cancer cell invasiveness" Oncogene 36(30):4380.
  20. Chang, H.-H., Liu, Y.-L., Lu, M.-Y., Jou, S.-T., Yang, Y.-L., Lin, D.-T., Lin, K.-H., Tzen, K.-Y. Yen, R.-F., Lu, C.-C., Liu, C.-J., Peng, S. S.-F., Jeng, Y.-M., Huang, S.-F., Lee, H., Juan, H.-F., Huang, M.-C., Liao, Y.-F., Lee, Y.-L.*, Hsu, W.-M.* (2017) "A multidisciplinary team care approach to improving outcomes in pediatric patients with high-risk neuroblastoma" Oncotarget 8(3):4360-72.
  21. Wang, Y.-T., Chiang, H.-H., Huang, Y.-S., Hsu, C.-L., Yang, P.-J., Juan, H.-F., Yang, W.-S.* (2016) "A link between adipogenesis and innate immunity: RNase-L promotes 3T3-L1 adipogenesis by destabilizing Pref-1 mRNA" Cell Death and Disease 7(11):e2458.
  22. Wu, C.-H., Hsu, C.-L., Lu, P.-C., Lin, W.-C., Juan, H.-F.*, Huang, H.-C.* (2016) "Identification of lncRNA functions in lung cancer based on associated protein-protein interaction modules" Scientific Reports 6:35939.
  23. Sahu, D., Hsu, C.-L., Lin, C.-C., Yang, T.-W., Hsu, W.-M., Ho, S.-Y., Juan, H.-F.*, Huang, H.-C.* (2016) "Co-expression analysis identifies long noncoding RNA SNHG1 as a novel predictor for event-free survival in neuroblastoma" Oncotarget 9(36): 58022-37.
  24. Hsu, C.-L., Chang, H.-Y., Chang, J.-Y., Hsu, W.-M., Huang, H.-C.* and Juan, H.-F.* (2016) "Unveiling MYCN regulatory networks in neuroblastoma via integrative analysis of heterogeneous genomics data" Oncotarget 7(24):36293-310.
  25. Lin, M.-T., Wang, C.-Y., Xie, H.-J., Cheung, C. H. Y., Hsieh, C.-H., Juan, H.-F., Chen, B.-S., C. Lin* (2016) "Novel utilization of terminators in the design of biologically adjustable synthetic filters" ACS Synthetic Biology 5(5):365-74.
  26. Jen, J., Lin, L.-L., Chen, H.-T., Liao, S.-Y., Lo, F.-Y., Tang, Y.-A., Hsu, H.-S., Salgia, R., Hsu, C.-L., Huang, H.-C., Juan, H.-F.*, Wang, Y.-C.* (2016) "Oncoprotein ZNF322A transcriptionally deregulates alpha-adducin, cyclin D1 and p53 to promote tumor growth and metastasis in lung cancer" Oncogene 35(18):2357-69.
  27. Liu, S.-Y., Shun, C.-T., Hung, K.-Y., Juan, H.-F., Hsu, C.-L., Huang, M.-C.*, Lai, I-R.* (2016) "Mucin glycosylating enzyme GALNT2 suppresses malignancy in gastric adenocarcinoma by reducing MET phosphorylation" Oncotarget 7(10):11251-62.
  28. Klionsky, D.-J., et al. (2016) "Guidelines for the use and interpretation of assays for monitoring autophagy" Autophagy 12(1):1-222.
  29. Hu, C.-W., Hsu, C.-L., Wang, Y.-C., Ishihama, Y., Ku, W-C., Huang, H.-C.* and Juan, H.-F.* (2015) "Temporal phosphoproteome dynamics induced by an ATP synthase inhibitor citreoviridin" Molecular & Cellular Proteomics 14(12):3284-98.
  30. Hsu, C.-L., Juan, H.-F.*, and Huang, H.-C.* (2015) "Characterization and functional analysis of differential coexpression networks" Scientific Reports5:13295.
  31. Lin, L.-L., Hsu, C.-L., Hu, C.-W., Ko, S.-Y., Hsieh, H.-L., Huang, H.-C.*,Juan, H.-F.* (2015) "Integrating phosphoproteomics and bioinformatics to study brassinosteroid-regulated phosphorylation dynamics in Arabidopsis"BMC Genomics 16:533. (Highly accessed)
  32. Lin, L.-L., Huang, H.-C.*, Juan, H.-F.* (2015) "Circadian systems biology in metazoa" Briefings in Bioinformatics (Mar 10 online)
  33. Huang, M.-J., Hu, R.-H., Chou, C.-H., Hsu, C.-L., Liu, Y.-W., Huang, J., Hung, J.-S., Lai, I-R., Juan, H.-F., Yu, S.-L., Wu, Y.-M.* and Huang, M.-C.*(2015) "Knockdown of GALNT1 suppresses malignant phenotype of hepatocellular carcinoma by suppressing EGFR signaling" Oncotarget6(8):5650-65.
  34. Lee, A. Y.-L.*, Chiu, Y.-C., Fang, W.-C., Cheng, C.-W., Kuo, C.-Y.,Juan, H.-F., Wu, S.-H.* and Kao, T.-Y.* (2015) "Mitochondrial Lon regulates apoptosis through the association with Hsp60-mtHsp70 complex" Cell Death & Disease 6:e1642.
  35. Lin, L.-L., Hsia, C.-R., Hsu, C.-L., Huang, H.-C.* and Juan, H.-F.* (2015) "Integrating transcriptomics and proteomics to show that tanshinone IIA suppresses cell growth by blocking glucose metabolism in gastric cancer cells" BMC Genomics 16(1):41.
  36. Chang, H.-Y., Li, M.-H., Huang, T.-C., Hsu, C.-L., Tsai, S.-R., Lee, S.-C.*, Huang, H.-C.* and Juan, H.-F.* (2015) "Quantitative proteomics reveals middle infrared radiation-interfered networks in breast cancer cells" Journal of Proteome Research 14(2):1250-62.
  37. Chang, H.-Y., Huang, T.-C., Chen, N.-N., Huang, H.-C.* and Juan, H.-F.*(2014) "Combination therapy targeting ectopic ATP synthase and 26s proteasome induces ER stress in breast cancer cells" Cell Death & Disease5:e1540.
  38. Chen, C.-Y., Ho, A., Huang, H.-Y., Juan, H.-F.* and Huang, H.-C.* (2014) "Dissecting the human protein-protein interaction network via phylogenetic decomposition" Scientific Reports 4:7153.
  39. Huang, C.-T., Oyang, Y.-J., Huang, H.-C.* and Juan, H.-F.* (2014) "MicroRNA-mediated networks underlie immune response regulation in papillary thyroid carcinoma" Scientific Reports 4:6495.
  40. Lin, L.-L., Huang, H.-C.*, Juan, H.-F.* (2014) "Deciphering molecular determinants of chemotherapy in gastrointestinal malignancy using systems biology approaches" Drug Discovery Today 19(9):1402-1409.
  41. Yang, K.-C., Hsu, C.-L., Lin, C.-C., Juan, H.-F.* and Huang, H.-C.* (2014) "Mirin: identifying microRNA regulatory modules in protein-protein interaction networks" Bioinformatics 30(17):2527-2528.
  42. Chen. C.-M., Chen, I.-C., Huang, Y.-C., Juan, H.-F., Chen, Y.-L., Chen, Y.-C., Lin, C.-H., Lee, L.-C., Lee, C.-M., Lee-Chen, G.-J., Lai, Y.-J., and Wu, Y.-R. (2014) "FBXO7 Y52C polymorphism as a potential protective factor in parkinson's disease" PLoS ONE 9(7):e101392.
  43. Hsieh, L.-C., Chen, J.-W., Wang, L.-Y., Tsang, Y.-M., Shueng, P.-W., Liao, L.-J., Lo, W.-C., Lin, Y.-C., Tseng, C.-F., Kuo, Y.-S., Jhuang, J.-Y., Tien, H.-J., Juan, H.-F., and Hsieh, C.-H. (2014) "Predicting the severity and prognosis of trismus after intensity-modulated radiation therapy for oral cancer patients by magnetic resonance imaging" PLoS ONE 9(3):e92561.
  44. Huang, W.-J., Tang, Y.-A., Chen, M.-Y, Wang, Y.-J., Hu, F.-H., Wang, T.-W., Chao, S.-W. Chiu, H.-W., Yeh, Y.-L., Chang, H.-Y., Juan, H.-F., Lin, P.*, and Wang, Y.-C.* (2014) "A histone deacetylase inhibitor YCW1 with antitumor and antimetastasis properties enhances cisplatin activity against non-small cell lung cancer in preclinical studies" Cancer Letter 346(1):84-93.
  45. Wu, P.-Y., Liao, Y.-F., Juan, H.-F., Huang, H.-C., Wang, B.-J., Lu, Y.-L., Yu, I-S., Shih, Y.-Y., Jeng, Y.-M., Hsu, W.-M.*, and Lee, H.* (2014) "Aryl hydrocarbon receptor downregulates mycn expression and promotes cell differentiation of neuroblastoma" PLoS ONE 9(2): e88795.
  46. Hu, C.-W., Tseng, C.-W., Chien, C.-W., Huang, H.-C., Ku, W.-C., Lee, S.-J.*, Chen, Y.-J.* and Juan, H.-F.* (2013) "Quantitative proteomics reveals diverse roles of miR-148a from gastric cancer progression to neurological development" Journal of Proteome Research 12(9):3993-4004.
  47. Wu, Y.-H., Hu, C.-W., Chien, C.-W., Chen, Y.-J., Huang, H.-C.* and Juan, H.-F.* (2013) "Quantitative proteomic analysis of human lung tumor xenografts treated with the ectopic ATP synthase inhibitor citreoviridin" PLoS ONE 8(8):e70642.
  48. Lin, L.-L., Wu, C.-C., Huang, H.-C.*, Chen, H.-J. Hsieh, H.-L.*, and Juan, H.-F.* (2013) "Identification of microRNA 395a in 24-epibrassinolide-regulated root growth of Arabidopsis thaliana using microRNA arrays" International Journal of Molecular Sciences 14:14270-14286.
  49. Lin, C.-C., Lee, C.-H., Fuh, C.-S., Juan, H.-F.* and Huang, H.-C.* (2013) "Link clustering reveals structural characteristics and biological contexts in signed molecular networks" PLoS ONE 8(6): e67089.
  50. Lee, C.-H., Kuo, W.-H., Lin, C.-C., Oyang, Y.-J., Huang, H.-C.* and Juan, H.-F.* (2013) "MicroRNA-regulated protein-protein interaction networks and their functions in breast cancer" International Journal of Molecular Sciences 14:11560-11606.
  51. Liaw, H.-H., Lin, C.-C., Juan, H.-F.* and Huang, H.-C.* (2013) "Differential microRNA regulation correlates with alternative polyadenylation pattern between breast cancer and normal cells" PLoS ONE 8(2): e56958.
  52. Chang, H.-Y., Shih, M.-H., Huang, H.-C., Tsai, S.-R., Juan, H.-F.*, Lee, S.-C.* (2013) "Middle infrared radiation induces G2/M cell cycle arrest in A549 lung cancer cells" PLoS ONE 8(1): e54117. (Featured on PLoS Blog)
  53. Fu, S.-C., Huang, H.-C., Horton, P.* and Juan, H.-F.* (2013) "ValidNESs: a database of validated leucine-rich nuclear export signals" Nucleic Acids Research 41(D1):D338-D343.
  54. Chen, C.-Y., Chen, S.-T., Juan, H.-F.* and Huang, H.-C.* (2012) "Lengthening of 3'UTR increases morphological complexity in animal evolution" Bioinformatics 28(24):3178-3181.
  55. Lu, K.-Y., Tao, S.-C., Yang, T.-C., Ho, Y.-H., Lee, C.-H., Lin, C.-C., Juan, H.-F., Huang, H.-C. , Yang, C.-Y., M,-S, Chen, H. Zhu*, and C.-S. Chen* (2012) "Profiling lipid-protein interactions using non-quenched fluorescent liposomal nanovesicles and proteome microarrays" Molecular & Cellular Proteomics 11(11):1177-1190.
  56. Hu, C.-W., Lin, M.-H., Huang, H.-C., Ku, W.-C., Yi, T.-H., Tsai, C.-F., Chen, Y.-J., Sugiyama, N., Ishihama, Y.*, Juan, H.-F.*, and Wu, S.-H.* (2012) "Phosphoproteomic analysis of Rhodopseudomonas palustris reveals the role of pyruvate phosphate dikinase phosphorylation in lipid production" Journal of Proteome Research 11:5362-5375.
  57. Lin, L.-L., Wang, Y.-H., Lai, C.-Y., Chau, C.-L., Su, G.-C., Yang, C.-Y., Lou, S.-Y., Chen, S.-K., Hsu, K.-H., Lai, Y.-L., Wu, W.-M., Huang, J.-L., Liao, C.-H. and Juan, H.-F.* (2012) "Systems biology of meridians, acupoints, and Chinese herbs in disease" Evidence-Based Complementary and Alternative Medicine 2012:372670.
  58. Lin, L.-L., Huang, H.-C., Ogihara, S., Wang, J.-T., Wu, M.-C., McNeil, P. L.*, Chen, C.-N.* and Juan, H.-F.* (2012) "Helicobacter pylori disrupts host cell membranes, initiating a repair response and cell proliferation" International Journal of Molecular Sciences 13:10176-10192.
  59. Lin, L.-L., Huang, H.-C.*, and Juan, H.-F.* (2012) "Revealing the molecular mechanism of gastric cancer marker Annexin A4 in cancer cell proliferation using exon arrays" PLoS ONE 7(9):e44615.
  60. Chang, H.-Y., Huang, H.-C., Huang, T.-C., Yang, P.-C.*, Wang, Y.-C.*, and Juan, H.-F.* (2012) "Ectopic ATP synthase blockade suppresses lung adenocarcinoma growth by activating the unfolded protein response" Cancer Research 72(18):4696-4706.
  61. Shih, Y.-Y., Nakagawara, A., Lee, H., Juan, H.-F., Jeng, Y.-M., Lin, D.-T., Yang, Y.-L., Tsay, Y.-G., Huang, M.-C., Pan, C.-Y., Hsu, W.-M., Liao, Y.-F.(2012) Calreticulin mediates nerve growth factor-induced neuronal differentiation. Journal of Molecular Neuroscience, 47 (3), pp. 571-581.
  62. Lin, L.-L., Huang, H.-C., Juan, H.-F.(2012) Discovery of biomarkers for gastric cancer: A proteomics approach (2012) Journal of Proteomics, 75 (11), pp. 3081-3097.
  63. Chang, M.-W., Lo, J.-M., Juan, H.-F., Chang, H.-Y., Chuang, C.-Y. (2012) Combination of RGD compound and low-dose paclitaxel induces apoptosis in human glioblastoma cells. PLoS ONE, 7 (5), art. no. e37935, .
  64. Tseng, C.-W., Huang, H.-C., Shih, A.C.-C., Chang, Y.-Y., Hsu, C.-C., Chang, J.-Y., Li, W.-H., Juan, H.-F.(2012) Revealing the anti-tumor effect of artificial miRNA p-27-5p on human breast carcinoma cell line T-47D. International Journal of Molecular Sciences, 13 (5), pp. 6352-6369.
  65. Lin, C.-C., Chen, Y.-J., Chen, C.-Y., Oyang, Y.-J., Juan, H.-F., Huang, H.-C.(2012) Crosstalk between transcription factors and microRNAs in human protein interaction network. BMC Systems Biology, 6, art. no. 18, .
  66. Hu, C.-W., Chang, Y.-L., Chen, S.J., Kuo-Huang, L.-L., Liao, J.C., Huang, H.-C., Juan, H.-F.(2011) Revealing the functions of the transketolase enzyme isoforms in rhodopseudomonas palustris using a systems biology approach. PLoS ONE, 6 (12), art. no. e28329, .
  67. Chen, S.-T., Jeng, Y.-M., Chang, C.-C., Chang, H.-H., Huang, M.-C., Juan, H.-F., Hsu, C.-H., Lee, H., Liao, Y.-F., Lee, Y.-L., Hsu, W.-M., Lai, H.-S.(2011) Insulin-like growth factor II mRNA-binding protein 3 expression predicts unfavorable prognosis in patients with neuroblastoma Cancer Science, 102 (12), pp. 2191-2198.
  68. Huang, T.-C., Chang, H.-Y., Chen, C.-Y., Wu, P.-Y., Lee, H., Liao, Y.-F., Hsu, W.-M., Huang, H.-C., Juan, H.-F.(2011) Silencing of miR-124 induces neuroblastoma SK-N-SH cell differentiation, cell cycle arrest and apoptosis through promoting AHR FEBS Letters, 585 (22), pp. 3582-3586.
  69. Tsai, S.-R., Huang, T.-C., Liang, C.-M., Chang, H.-Y., Chang, Y.-T., Huang, H.-C., Juan, H.-F., Lee, S.-C.(2011) The effect of narrow bandwidth infrared radiation on the growth of Escherichia coli. Applied Physics Letters, 99 (16), art. no. 163704, .
  70. Chen, C.-M., Lin, C.-H., Juan, H.-F., Hu, F.-J., Hsiao, Y.-C., Chang, H.-Y., Chao, C.-Y., Chen, I.-C., Lee, L.-C., Wang, T.-W., Chen, Y.-T., Chen, Y.-T., Lee-Chen, G.-J., Wu, Y.-R.(2011) ATP13A2 variability in Taiwanese Parkinson's disease American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics, 156 (6), pp. 720-729.
  71. Lee, C.-H., Huang, H.-C., Juan, H.-F.(2011) Reviewing ligand-based rational drug design: The search for an ATP synthase inhibitor. International Journal of Molecular Sciences, 12 (8), pp. 5304-5318.
  72. Tseng, C.-W., Lin, C.-C., Chen, C.-N., Huang, H.-C., Juan, H.-F.(2011) Integrative network analysis reveals active microRNAs and their functions in gastric cancer. BMC Systems Biology, 5, art. no. 99,
  73. Tseng, C.-W., Yang, J.-C., Chen, C.-N., Huang, H.-C., Chuang, K.-N., Lin, C.-C., Lai, H.-S., Lee, P.-H., Chang, K.-J., Juan, H.-F.(2011) Identification of 14-3-3β in human gastric cancer cells and its potency as a diagnostic and prognostic biomarker Proteomics, 11 (12), pp. 2423-2439.
  74. Juan, H.-F., Hsu, J.-W., Huang, H.-C., Chen, S.-T., Wong, C.-H.(2011) Ganoderma lucidum polysaccharides induce macrophage-like differentiation in human leukemia THP-1 cells via caspase and p53 activation. Evidence-based Complementary and Alternative Medicine, 2011, art. no. 358717, .
  75. Chen, C-Y, Chen, S.-T., Fuh, C.-S. Juan, H.-F.*, Huang H.-C.* (2011) "Coregulation of Transcription Factors and microRNAs in Transcriptional Regulatory Network" BMC Bioinformatics 12 (Suppl 1):S41.
  76. Chen, J.-Y., Huang, S.-M., Tang, Y.-A., Juan, H.-F., Wu, L.-W., Sun, Y.-C., Wang, S.-C., Wu, K. W., Balraj, G., Chang, T.-T., Li, W.-S.*, Cheng, H.-C.*, Wang, Y.-C.* (2011) "A novel sialyltransferase inhibitor suppresses FAK/paxillin and angiogenesis signaling and cancer metastasis" Cancer Research 71:473-483.
  77. Lin, C.-C., Hsiang, J.-T., Wu, C.-Y., Oyang, Y.-J., Juan, H.-F. * ,Huang H.-C. * (2010) "Dynamic functional modules in co-expressed protein interaction networks of dilated cardiomyopathy" BMC Systems Biology 4:138.
  78. Chang, H.-H., Lee, H.-Y., Hu, M.-K., Tsao, P.-N., Juan, H.-F. , Huang, M.-C., Shih, Y.-Y., Wang, B.-J., Jeng, Y.-M., Chang, C., Huang, S.-F., Y.-G. Tsay, Hsieh, F.-J., Lin, K.-H. * , Hsu, W.-M. * , and Liao, Y.-F * . (2010) "Notch1 expression predicts an unfavorable prognosis and serves as a therapeutic target of patients with neuroblastoma" Clinical Cancer Research 16:4411-4420.
  79. Hsu, J.-W., Huang H.-C. , Chen, S.-T., Wong, C.-H. , Juan, H.-F. * (2009) "Ganoderma lucidum polysaccharides induce macrophage-like differentiation in human leukemia THP-1 cells via caspase and p53 activation" Evidence-Based Complementary and Alternative Medicine ; doi: 10.1093/ecam/nep107
  80. Hwang Y.-C., Lin C.-C., Chang J.-Y., Mori H., Juan, H.-F. * , Huang H.-C. * (2009) "Predicting essential genes based on network and sequence analysis" Molecular BioSystems 5:1672–1678.
  81. Lin, C.-C., Juan, H.-F. , Hsiang, J.-T., Hwang, Y.-C., Mori, H. * , Huang, H.-C. * (2009) "Essential core of protein-protein interaction network in Escherichia coli " Journal of Proteome Research 8(4):1925-1931.
  82. Chang, Y.-M., Juan, H.-F. , Lee, T.-Y., Chang, Y.-Y., Yeh, Y.-M., Li, W.-H. * , Shih, A. C.-C. (2008) "Prediction of human miRNAs using tissue-selective motifs in 3' UTRs" Proc. Natl. Acad. Sci. U S A 105, 17061-17066. ( Highlighted in Nature Biotechnology and in Science-Business eXchange (SciBX) )
  83. Fang, Y.-C., Huang, H.-C. , Chen, H.-H. and Juan, H.-F. * (2008) "TCMGeneDIT: a database for associated traditional Chinese medicine, gene and disease information using text mining" BMC Complementary and Alternative Medicine 8:58.
  84. W.-M. Hsu, H.-Y. Lee, Juan, H.-F. , Y.-Y. Shih, B-J. Wang, C.-Y. Pan, Y.-M. Jeng, H.-H. Chang, M.-Y. Lu, K.-H. Lin, H.-S. Lai, W.-J. Chen, Y.-G. Tsay * , Y.-F. Liao * , F.-J. Hsieh * (2008) "Identification of GRP75 as an Independent Favorable Prognostic Marker of Neuroblastoma by a Proteomics Analysis" Clinical Cancer Research 14:6237-6245.
  85. Hsu, C.-W., Juan, H.-F. * , Huang, H.-C. * (2008) "Characterization of microRNA-Regulated Protein-Protein Interaction Network" Proteomics 8:1975-1979.
  86. Lin, L.-L., C.-N. Chen*, Lin, W.-C., Lee, P.-H., Chang, K.-J., Lai, Y.-P., Wang, J.-T., Juan, H.-F. * (2008) "Annexin A4: A novel molecular marker for gastric cancer with Helicobacter pylori infection using proteomics approach " Proteomics: clinical applications 2:619-634.
  87. Chen, S.-T., Pan, T.-L., Juan, H.-F. , Chen, T.-Y., Lin, Y.-S., Huang, C.-M. * (2008) "Breast Tumor Microenvironment: Proteomics Highlights the Treatments Targeting Secretome and Extracellular Matrix" Journal of Proteome Research 7:1379-1387.
  88. Huang, T.-C., Chang, H.-Y., Hsu, C.-H., Kuo, W.-H., Chang, K.-J., Juan, H.-F. * (2008) "Targeting Therapy on Breast Carcinoma by ATP Synthase Inhibitor Aurovertin B" Journal of Proteome Research 7:1433-1444. ( Science Daily news & American Chemical Society weekly news )
  89. Chen, H.-W., Huang, H.-C., Lin, Y.-S., Chang, K.-J., Kuo, W.-H., Hwa, H.-L., Hsieh, F.-J. * , Juan, H.-F. * (2008) "Comparison and Identification of Estrogen-Receptor Related Gene Expression Profiles in Breast Cancer of Different Ethnic Origins" Breast Cancer: Basic and Clinical Research 1:35-49.
  90. Tan, Y-H., Lee, K.-H., Sun, Y.-C., Juan, H.-F. * , Y.-C. Wang * (2008) "Cytotoxicity and proteomics analyses of OSU 03013 in lung cancer" Clinical Cancer Research 14:1823-1830.
  91. Fang, Y.-C., Huang, H.-C. * , Juan, H.-F. * (2008) "MeInfoText: Associated Gene Methylation and Cancer Information from Text Mining" BMC Bioinformatics 9:22.
  92. Huang, B., Ni, K.-C., Chen, S.-L., Juan, H.-F. * , Chen Y.-M. * (2008) "Elucidating the Growth Regulation of Brassinosteroids in Mung Bean Epicotyls using a Proteomics Approach" Proteomics Research Journal 1: 1-18.
  93. Lien, H.-C., Hsiao, Y.-H., Lin, Y.-S., Yao , Y.-T., Juan, H.-F. , Kuo, W.-H., Hung, M.-C., Chang, K.-J., Hsieh, F.-J. * (2007) "Molecular Signatures of Metaplastic Carcinoma of the Breast by Large-Scale Transcriptional Profiling: Identification of Genes Potentially Related to Epithelial-Mesenchymal Transition." Oncogene 26:7859-7871.
  94. Cheng, K.-C., Huang, H.-C., Chen, J.-H., Hsu, J.-W., Cheng, H.-C., Ou, C.-H., Yang, W.-B., Chen, S.-T., Wong, C.-H. and Juan, H.-F. * (2007) " Ganoderma lucidum polysaccharides in human monocytic leukemia cells: from gene expression to network construction" BMC Genomics 8:411.
  95. Huang, T.-C., Huang, H.-C., Chang, C.-C., Chang, H.-Y., Ou, C.-H., Hsu, C.-H., Chen, S.-T. and Juan, H.-F. * (2007) "An Apoptosis-related Gene Network Induced by Novel Compound-cRGD in Human Breast Cancer Cells." FEBS Letters 581:3517-3522.
  96. Leu, J.-H., Chang, C.-C., Wu, J.-L., Hsu, C.-W., Hirono, I. , Aoki, T., Juan, H.-F. , Lo, C.-F., Kou, G.-H. * , Huang H.-C. * (2007) "Comparative analysis of differentially expressed genes in normal and white spot syndrome virus infected Penaeus monodon ." BMC Genomics 8:120.
  97. Fang, Y.-C., Sun, W.-H.*, Wu, L.-C., Huang, H.-D., Juan, H.-F. , Horng, J.-T.* (2006) "RINGdb: An integrated database for G protein-coupled receptors and regulators of G protein signaling." BMC Genomics 7 :317.
  98. Tseng, H.-W., Juan, H.-F. , Huang, H.-C., Lin, J. Y.-C., Sinchaikul, S., Chen , C.-F., Chen, S.-T. * , Wang * , G.-J. (2006) "A systems biology study of lipopolysaccharide-stimulated responses in rat aortic endothelial cell." Proteomics 6 :5915-5928.
  99. Chen, Y.-R., Juan, H.-F. , Huang, H.-C., Huang, H.-H., Lee, Y.-J., Liao, M.-Y., Tseng, C.-W., Lin, L.-L., M.-Y. Chen, J.-Y., Wang, M.-J., J.-H. Chen * , Y.-J. Chen * (2006) "Quantitative Proteomic and Genomic Profiling Reveals Metastasis-Related Protein Expression Patterns in Gastric Cancer Cells." Journal Proteome Research 5 :2727-2742.
  100. Huang, B., Chu , C.-H., Chen, S.-L., Juan, H.-F. * and Chen, Y.-M. * (2006) "Proteomics Study of Mung Bean Epicotyl Regulated by Brassinosteroid under Chilling Condition." Cellular & Molecular Biology Letters 11 :264-278.
  101. Juan, H.-F. * , Wang, I-H., Huang, T.-C., Li, J.-J., Chen, S.-T., Huang, H.-C. (2006) " Proteomics analysis of a novel compound – cyclic RGD in breast carcinoma cell line MCF-7. " Proteomics 6 :2991-3000. ( Cover Picture )
  102. Lee, T.-Y., Horng, J.-T., Juan, H.-F. , Huang, H.-D., Wu, L.-C., Lin, F.-M., Huang, H.-C (2006) "An agent-based system to discover protein-protein interactions, identify protein complexes and proteins with multiple peptide mass fingerprints." Journal of Computational Chemistry 27 :1020-1032.
  103. Horng, J.-T., Lee, T.-Y., Wu, L.-C., Huang, H.-D., Juan, H.-F. , Lin, F.-M. (2005) "MultiProtIdent: Identifying Proteins Using Database Search and Protein-Protein Interactions." Journal Proteome Research 4 :690-697.
  104. Juan, H.-F. * , Chang, S.-C., Huang, H.-C., Chen, S.-T. (2005) "A New Application of Microwave Technology to Proteomics." Proteomics 5 :840-842.
  105. Wu, C.-C., Huang, H.-C., Juan, H.-F. , Chen, S.-T. (2004) "GeneNetwork: an interactive tool for reconstruction of genetic networks using microarray data. " Bioinformatics 20 : 3691-3693.
  106. Chen, C.-Y., Oyang, Y.-J., Juan, H.-F. (2004) " Incremental generation of summarized clustering hierarchy for protein family analysis. " Bioinformatics 20 :2586-96.
  107. Juan, H.-F. , Chen, J.-H., Hsu, W.-T., Huang, S.-C., Chen, S.-T., Lin, J. Y. C., Chang, Y.-W. Chiang, C.-Y., Wen, L.-L., Chan, D.-C., Liu, Y.-C., Chen, Y.-J. (2004) "Identification of tumor-associated plasma biomarkers using proteomic techniques: from mouse to human." Proteomics 4 : 2766-2775. ( Cover Picture )
  108. Wu, C.-Y. Jan, J.-T., Ma, H.-H., Kuo, C.-J., Juan, H.-F. , Cheng, Y.-S. E., Hsu, H.-H., Huang, H.-C., Wu, D., Brik, A., Liang, F.-S., Liu, R.-S., Fang , J.-M., Chen, S.-T., Liang , P.-H. and Chi-Huey Wong (2004) "Small molecules targeting Severe Acute Respiratory Syndrome (SARS) human coronavirus." Proc. Natl. Acad. Sci. U S A 101 : 10012-10017.
  109. Juan, H.-F. , Liu, H.-L., Hsu, J.-P. (2004) "Recent developments in structural proteomics: from protein identifications and structure determinations to protein-protein interactions" Current Proteomics 1 : 183-197. (Invited review paper)
  110. Chang, D. T.-H, Chen, C.-Y., Chung, W.-C., Oyang, Y.-J., Juan, H.-F. , Huang, H.-C. (2004) "ProteMiner-SSM: A web server for efficient analysis of similar protein tertiary substructures" Nucleic Acids Research. 32 : W76-82.
  111. Wu, S.-F., Liu, T.-M., Lin, Y.-C., Sytwu, H.-K., Juan, H.-F. , Chen, S.-T., Shen, K.-L., Hsi, S.-C., Hsieh, S.-L. (2004) "Immunomodulatory effect of decoy receptor 3 on the differentiation and function of bone-marrow-derived dendritic cells in non-obese diabetic mice: From regulatory mechanism to clinical implication" Journal of Leukocyte Biology 75 : 1-14.
  112. Juan, H.-F. , Lin, J. Y. C., Chang, W. H., Wu, C. Y., Pan, T. L. Tseng, M. J., Khoo, K. H. and Chen, S. T. (2002) "Biomic study of human myloid leukemia cell (HL-60) differentiated to macrophage using DNA array , proteomic, and bioinformatic analytical methods" Electrophoresis 23 : 2490 -2504.
  113. Sinchaikul, S., Sookkheo, B., Topanuruk, S., Juan, H.-F. , Phutrakul, S., and Chen, S.-T. (2002) "The bioinformatics, functional genomics, and proteomics study of Bacillus sp." J. Chromatogr B 771 : 261-287.
  114. Xu, D.-H., Juan, H.-F. , Nohda, M., Ban, T. (2001) “Optimization of AFLP method in wheat and its application to QTL mapping for spike characters” Breeding Research 3: 25.
  115. Juan, H.-F., Hung, C.-C., Wang, K.-T., Chiou, S.-H.* (1999) "Comparison of three classes of snake neurotoxins by homology modeling and computer simulation graphics." Biochem Biophys Res Commun. 257 : 500-510.

研討會論文 Conference
專利 Patent
  1. Li, W.-S., Wang, Y.-C., Juan, H.-F. "Certain Lithocholic acid analogues that inhibit sialytransferase" ROC I 369361, 2012/8/1-2026/7/5.
  2. Juan, H.-F., Mori, H., Chang, H.-Y., Huang, H.-C., Huang, T.-C., Liao, J.C., "Alcohols tolerant Escherichia coli and methods of production thereof" ROC I 379901, 2012/12/21-2028/10/28.
  3. Juan, H.-F., Chen, C.-N., Tseng, C.-W., Chang, K.-J. "Method for prognosis of gastric cancer" ROC I 399541, 2013/6/21-2029/5/26.
  4. Li, W.-S., Wang, Y.-C., Juan, H.-F. "Lithocholic acid analogues that inhibit sialyltransferase" US 08940719, 2015/1/27-2035/1/28.

專書篇章 Book Chatpers
  1. Juan, H.-F. "Proteomic techniques and their applications" in Biomolecular and Bioanalytical Techniques: Theory, Methodology and Applications, Edited by Vasudevan Ramesh (John Wiley & Sons, Inc., UK), in press.
  2. Siddiqui, H., Sami, F., Juan, H.-F.* and Hayat, S.* "Brassinosteroid Regulated Physiological Process: An Omics Perspective" Brassinosteroids: Plant Growth and Development, ed. By Shamsul Hayat, Dr. Mohammad Yusuf, Dr. Renu Bhardwaj & Dr. Andrzej Bajguz (Springer Nature, Singapore), in press.
  3. Juan, H.-F. and Huang, H.-C. (2018) A Practical Guide to Cancer Systems Biology (World Scientific Publishing, Singapore)
  4. Juan, H.-F. (2017) "Data Sources for herbal and traditional medicines" in Computational Systems Pharmacology and Toxicology, Edited by Dale Johnson and Rudy J Richardson (The Royal Society of Chemistry, Cambridge, UK), pp. 243-260.
  5. Juan, H.-F. and Huang, H.-C. (2012) Systems Biology: Applications in cancer-related research (World Scientific Publishing, Singapore).
  6. Juan, H.-F. (2011) "Transcriptomics and proteomics study in regulation of brassinosteroids" in Brassinosteroids: A Class of Plant Hormone, ed. Shamsul Hayat and Aqil Ahmad (Springer, Netherlands), pp. 393-402.
  7. Juan, H.-F. and Huang, H.-C. (2007) "Bioinformatics: Microarray Data Clustering and Functional Classification" in Microarrays (2nd e ed): Applications and Data Analysis, ed. Jang B. Rampal (The humana press inc.), pp. 405-416.
  8. 陳水田、曾銘仁、阮雪芬等 (2003) 基因體科學入門, 藝軒. . [A Primer of Genome Science, Gibson, G. and Muse, S. V., Sinauer Associates Inc. (2001)]

科普文章 Popular Science Articles
  1. 阮雪芬、黃宣誠 (2016). 解析複雜的生命現象—系統生物學. 科學月刊六月號558: 436-441 (封面故事)
  2. 鄞偈帆、高士傑、阮雪芬 (2015). 丹參的效用―從心血管疾病的治療到抗癌. 科技報導七月號403期 (焦點話題)
  3. 張心儀、黃翠琴、阮雪芬 (2009). 大腸桿菌與新能源開發. 科學月刊四月號472: 289-290 (封面故事)
  4. 林怡杏、連晃駿、章麗雲、華筱玲、徐明洸、郭文宏、阮雪芬、張金堅、謝豐舟 (2008). DNA微陣列晶片在乳癌診斷之最新發展. 當代醫學35: 453-459.
  5. 阮雪芬 (2005). 蛋白質體學的介紹. 化工52: 14-22.
  6. 阮雪芬、陳水田、朱延和 (2002). 王光燦院士--臺灣生物有機化學研究的先驅者。科學發展月刊 357: 60-65.
  7. 阮雪芬、陳益明 (1993). 植物抵抗疾病的免疫反應. 科學農業. 41: 49-53.

開設課程

  • 生物資訊學
  • 系統生物學專題討論
  • 系統生物學
  • 普通生物學
  • 基因體學