This laboratory aims to develop technologies enabling cell-specific delivery of nucleic acid therapeutic agents for personalized cancer therapy. Oligonucleotides of different sequences can fold into different conformations to bind to their protein targets with high specificity and affinity. These structured oligonucleotides are known as aptamers. This laboratory has integrated bioinformatics, genomics, and proteomics technologies to identify several surface marker proteins on cancer cells. Functional aptamers specific to cancer cell surface marker proteins are employed to deliver siRNAs and/or DNAzymes into cancer cells by the receptor mediated endocytosis process to knock down the metastasis and cell proliferation associated signaling pathways. Cocktail therapy using cancer cell-specific aptamers conjugated with different allele-specific and/or transcript-specific nucleic acid therapeutic agents against various pivotal gene transcripts are being devised to knock down signaling pathways involved in the metastasis cascade and cell proliferation. The goal of these studies is to develop novel therapeutics to inhibit metastasis and to eradicate cancer cells with minimal side effects by synthetic lethal killing and allele-specific or transcript-specific therapeutic agents.
標靶療法為近年來癌症治療的一大突破。然而許多標靶基因不僅存在於癌細胞也存在於正常細胞,欲針對癌細胞來拮抗其含有的標靶基因而不影響正常細胞仍為醫療研究的一大挑戰。適體(aptamer)為核酸分子,可依序列不同而形成許多穩定的結構,如同抗體可專一地與特定標的分子結合。 本實驗室研究方向為研發新科技來搜尋癌細胞特定的表面蛋白質、受體、癌轉移及生長相關基因並驗證其功能,同時篩選可辨識癌細胞表面特定受體的適體來專一地辨識並活化癌細胞特有表面受體。辨識癌細胞表面受體的適體分子可用來傳輸siRNAs或DNAzymes,並利用受體的endocytosis作用將siRNA或DNAzyme分子送入細胞內來抑制癌細胞生長及轉移相關基因的表達。目前研究方向為利用多種不同適體來輸送前述核酸藥劑同時作用在癌細胞內多種標靶基因、對偶基因、轉錄異型等。本實驗室研究目標為開創一個全新的癌症治療方法,針對癌細胞獨有的轉移相關基因、對偶基因、偶合毀滅(synthetic lethality)對應基因來發展核酸藥劑,以期消滅癌細胞但避免對正常細胞產生副作用。
1. | Tzu-Hung Hsiao, Chien-Hong Lin, Te-Tsui Lee, Ji-Yen Cheng, Pei-Kuen Wei, Eric Y. Chuang, Konan Peck Verifying expressed transcript variants by detecting and assembling stretches of consecutive exons NUCLEIC ACIDS RESEARCH 38, e187 (2010-08) [JCR] [WOS] |
2. | Yeh-Hsing Lao, Lin-Chi Chen, Yi-Chung Chang, Chun-Wei Chi, Konan Peck Applications of Microarray in Aptamer Study Instruments Today 31(2), 95-102 (2009-10) [JCR] [WOS] |
3. | Y. C. Chang, W. C. Kao, W. Y. Wang, W. Y. Wang, R. B. Yang, K. Peck Identification and characterization of oligonucleotides that inhibit Toll-like receptor 2-associated immune responses FASEB JOURNAL 23(9), 3078-3088 (2009-09) [JCR] [WOS] |
4. | Lao YH, Peck K, Chen LC Enhancement of Aptamer Microarray Sensitivity through Spacer Optimization and Avidity Effect. ANALYTICAL CHEMISTRY 81,1747-1754 (2009-03) [JCR] [WOS] |
5. | K. Peck, L. C. Chen, S. C. Tzeng, Y. S. Kao, W. C. Kao DNA aptamer for molecular recognition and protein expression profiling JOURNAL OF GENETICS AND MOLECULAR BIOLOGY 19, 263-269 (2008) [JCR] [WOS] |
6. | K. Peck Kallikreins and Cancer Encyclopedia of Cancer; 2nd ed 1587-1590 (2008) [JCR] [WOS] |
7. | Chou CC, Peck K Design and fabrication of spotted long oligonucleotide microarrays for gene expression analysis. Methods in molecular biology (Clifton, N.J.) 381, 213-225 (2007) [JCR] [WOS] |
8. | M. J. Chen, P. P. Chiou, P. Lin, S. Siri, K. Peck and T. T. Chen Suppression of growth and cancer-induced angiogenesis of aggressive human breast cancer cells (MDA-MB-231) on the chorioallantoic membrane of developing chicken embryos by E-peptide of pro-IGF-I JOURNAL OF CELLULAR BIOCHEMISTRY 101, 1316-1327 (2007) [JCR] [WOS] |
9. | Y. A. Chen, C. C. Chou, X. Lu, E. H. Slate, K. Peck, W. Xu, E. O. Voit and J. S. Almeida A multivariate prediction model for microarray cross-hybridization BMC BIOINFORMATICS 7, 101 (2006) [JCR] [WOS] |
10. | A. Semenyuk, M. Ahnfelt, C. Estmer, Yong-Hao, A. Foldesi, Y. S. Kao, H. H. Chen, W. C. Kao, K. Peck and M. Kwiatkowski Cartridge-based high-throughput purification of oligonucleotides for reliable oligonucleotide arrays ANALYTICAL BIOCHEMISTRY 356(1), 132-141 (2006) [JCR] [WOS] |
11. | C. C. Chou, T. T. Lee, C. H. Chen, H. Y. Hsiao, Y. L. Lin, M. S. Ho, P. C. Yang and K. Peck Design of microarray probes for virus identification and detection of emerging viruses at the genus level BMC BIOINFORMATICS 7, 232 (2006) [JCR] [WOS] |
12. | Y. P Sher, C. C. Chou, R. H. Chou, H. M. Wu, W. S. Chang, C. H. Chen, P. C. Yang, C. W. Wu, C. L Yu and K Peck Human Kallikrein 8 Protease Confers A Favorable Clinical Outcome in Non-Small Cell Lung Cancer by Suppressing Tumor Cell Invasiveness CANCER RESEARCH 66, 11763-11770 (2006) [JCR] [WOS] |
13. | Huey-Jiuan Juang, Te-Chang Lee, Rong-Nan Huang, Jeou-Yuan Chen, and Konan Peck Identification of p53-regulated Genes in Human Cancer Cells by Genome-wide Transcription Profiling with cDNA Microarray JOURNAL OF GENETICS AND MOLECULAR BIOLOGY 16, 63-71 (2005) [JCR] [WOS] |
14. | Y. P. Sher, J. Y. Shih, P. C. Yang, S. R. Roffler, Y. W. Chu, C. W. Wu, C. L. Yu and K. Peck Prognosis of Non-Small Cell Lung Cancer Patients by Detecting Circulating Cancer Cells in the Peripheral Blood with Multiple Marker Genes CLINICAL CANCER RESEARCH 11, 173-179 (2005) [JCR] [WOS] |
15. | J. L. Huang, H. T. Lin, Y. M. Wang, Y. C. Yeh, K. Peck, B. L. Lin, H. W. Liu, A. Chen and C. S. Lin Rapid and sensitive detection of multiple genes from the SARS-Coronavirus using quantitative RT-PCR with dual system JOURNAL OF MEDICAL VIROLOGY 77, 151-158 (2005) [JCR] [WOS] |
16. | M. C. Shih, K. Peck, W. L. Chan, Y. P. Chu, J. C. Chen, C. H. Tsai and J. G. Chang SARS-CoV infection was from at least two origins in the Taiwan area INTERVIROLOGY 48, 124-132 (2005) [JCR] [WOS] |
17. | C. H. Liu, K. Peck, J. D. Huang, M. S. Lin, C. H. Wang, W. P. Hsu, H. W. Wang, H. L. Lee and M. L. Lai Screening CYP3A SNPs in a Han Chinese population with a genotyping chip PHARMACOGENOMICS 6, 731-747 (2005) [JCR] [WOS] |
18. | S. L. Yu, H. W. Chen, P. C. Yang, K. Peck, M. H. Tsai, J. J. W. Chen and F. Y. Lin Differential gene expression in gram-negative and gram-positive sepsis AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE 169, 1135-1143 (2004) [JCR] [WOS] |
19. | H. W. Chen, S. L. Yu, W. J. Chen, P. C. Yang, C. T. Chien, H. Y. Chou, H. N. Li, K. Peck, C. H. Huang, F. Y. Lin, J. J. W. Chen and Y. T. Lee Dynamic changes of gene expression profiles during postnatal heart development in mice Heart 90, 927-934 (2004) [JCR] [WOS] |
20. | C. C. Chou, C. H. Chen, T. T Lee and K. Peck Optimization of probe length and the number of probes per gene for optimal microarray analysis of gene expression Nucleic Acids Res 32, e99 (2004) [JCR] [WOS] |
21. | P. C. Chang, K. Peck Design and assessment of a fast algorithm for identifying specific probes for human and mouse genes Bioinformatics 19, 1311-1317 (2003) [JCR] [WOS] |
22. | S. Li, J. Lao, B. P. Chen, Y. S. Li, Y. Zhao, J. Chu, K. D. Chen, T. C. Tsou, K. Peck and S. Chien Genomic analysis of smooth muscle cells in 3-dimensional collagen matrix FASEB J 17, 97-99 (2003) [JCR] [WOS] |
23. | Cheng-Chung Chou and Konan Peck DNA microarrays and their applications Instruments Today 23(5), 5-13 (2002-04) [JCR] [WOS] |
24. | L. H. Yih, K. Peck and T. C. Lee Changes in gene expression profiles of human fibroblasts in response to sodium arsenite treatment Carcinogenesis 23, 867-876 (2002) [JCR] [WOS] |
25. | J. Y. Cheng, H. H. Chen, Y. S. Kao, W. C. Kao and K. Peck High throughput parallel synthesis of oligonucleotides with 1536 channel synthesizer Nucleic Acids Res 30, e93 (2002) [JCR] [WOS] |
26. | W. Huang, Y. P. Sher, K. Peck and Y. C. Fung Matching gene activity with physiological functions PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 99, 2603-2608 (2002) [JCR] [WOS] |
27. | Ji-Yen Cheng and Konan Peck Fabrication of oligonucleotide microarray and its applications in genetic assay Instruments Today 22(5), 8-19 (2001-04) [JCR] [WOS] |
28. | S. Ang, C. Z. Lee, K. Peck, M. Sindici, U. Matrubutham, M. A. Gleeson and J. T. Wang Acid-induced gene expression in Helicobacter pylori: study in genomic scale by microarray Infect Immun 69, 1679-1686 (2001) [JCR] [WOS] |
29. | K. Peck, Y. P. Sher Application of Enzyme Colorimetry for cDNA Microarray Detection In: BioChip Technology 325-340 (2001) [JCR] [WOS] |
30. | K. Peck, Y. P. Sher cDNA Microarrays on Nylon Filter Membrane With Colorimetric Detection DNA Microarrays: Gene Expression Applications 35-54 (2001) [JCR] [WOS] |
31. | J. Y. Shih, S. C. Yang, T. M. Hong, A. Yuan, J. J. Chen, C. J. Yu, Y. L. Chang, Y. C. Lee, K. Peck, C. W. Wu and P. C. Yang Collapsin response mediator protein-1 and the invasion and metastasis of cancer cells JOURNAL OF THE NATIONAL CANCER INSTITUTE 93, 1392-1400 (2001) [JCR] [WOS] |
32. | W. Huang, Y. P. Sher, K. Peck and Y. C. Fung Correlation of gene expression with physiological functions: Examples of pulmonary blood vessel rheology, hypoxic hypertension, and tissue remodeling Biorheology 38, 75-87 (2001) [JCR] [WOS] |
33. | K. Yoneda, K. Peck, M. M. Chang, K. Chmiel, Y. P. Sher, J. Chen, P. C. Yang, Y. Chen and R. Wu Development of high-density DNA microarray membrane for profiling smoke- and hydrogen peroxide-induced genes in a human bronchial epithelial cell line AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE 164, S85-89 (2001) [JCR] [WOS] |
34. | J. J. Chen, K. Peck, T. M. Hong, S. C. Yang, Y. P. Sher, J. Y. Shih, R. Wu, J. L. Cheng, S. R. Roffler, C. W. Wu and P. C. Yang Global analysis of gene expression in invasion by a lung cancer model Cancer Res 61, 5223-5230 (2001) [JCR] [WOS] |
35. | M.M.J. Chang, Y. Chen, Y. H. Zhao, R. Wu, C. Li and K. Peck High-Density DNA Microarray Membranes to Study Gene Expression Patterns Associated with Human Airway Epithelial Cell Differentiation in Culture In: Cilia and Mucus: From Development to Respiratory Defense. Marcel Dekker, Inc., New York 225-238 (2001) [JCR] [WOS] |
36. | T. M. Hong, J. J. Chen, K. Peck, P. C. Yang and C. W. Wu p53 amino acids 339-346 represent the minimal p53 repression domain J Biol Chem 276, 1510-1515 (2001) [JCR] [WOS] |
37. | W. Huang, Y. P. Sher, D. Delgado-West, J. T. Wu, K. Peck and Y. C. Fung Tissue remodeling of rat pulmonary artery in hypoxic breathing. I. Changes of morphology, zero-stress state, and gene expression Ann Biomed Eng 29, 535-551 (2001) [JCR] [WOS] |
38. | T. M. Hong, P. C. Yang, K. Peck, J. J. Chen, S. C. Yang, Y. C. Chen and C. W. Wu Profiling the downstream genes of tumor suppressor PTEN in lung cancer cells by complementary DNA microarray AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY 23, 355-363 (2000) [JCR] [WOS] |
39. | T. C. Chang, C. T. Kuo, C. .C Chiang, J. Y. Cheng, C. S. Yan and K. Peck Investigation of guanine-rich DNA telomeric structure by a covalently linked BODIPY dye Phys Chem Chem Phys 1, 3783-3787 (1999) [JCR] [WOS] |
40. | F. Bertucci, K. Bernard, B. Loriod, Y. C. Chang, S. Granjeaud, D. Birnbaum, C. Nguyen, K. Peck and B. R. Jordan Sensitivity issues in DNA array-based expression measurements and performance of nylon microarrays for small samples Hum Mol Genet 8, 1715-1722 (1999) [JCR] [WOS] |
41. | K. Peck, Y. P. Sher, J. Y. Shih, S. R. Roffler, C. W. Wu and P. C. Yang Detection and quantitation of circulating cancer cells in the peripheral blood of lung cancer patients Cancer Res 58, 2761-2765 (1998) [JCR] [WOS] |
42. | J. J. Chen, R. Wu, P. C. Yang, J. Y. Huang, Y. P. Sher, M. H. Han, W. C. Kao, P. J. Lee, T. F. Chiu, F. Chang, Y. W. Chu, C. W. Wu and K. Peck Profiling expression patterns and isolating differentially expressed genes by cDNA microarray system with colorimetry detection Genomics 51, 313-324 (1998) [JCR] [WOS] |
43. | C. T. Kuo, C. C. Chiang, J. Yu, K. Peck and T. C. Chang Satellite hole investigation of binding mechanism of dipyrrometheneboron difluoride (BODIPY) derivative and oligonucleotide in glycerol-water glass Journal of the Chemical Society, Faraday Transactions 94, 1989-1994 (1998) [JCR] [WOS] |
44. | K. Peck, S. L. Wung, G. S. Chang, J. J. Yen and Y. Z. Hsieh Restriction mapping of genes by capillary electrophoresis with laser-induced fluorescence detection Anal Chem 69, 1380-1384 (1997) [JCR] [WOS] |
45. | T. C. Chang, C. C. Chiang and K. Peck Conformational Structures of Dye-Oligonucleotides Studied by Satellite Holes In: OSA TOPS on Biomedical Optical Spectroscopy and Diagnostics. Optical Society of America 3, 245-249 (1996) [JCR] [WOS] |
46. | J. J. Chen, K. Peck Non-radioisotopic differential display method to directly visualize and amplify differential bands on nylon membrane Nucleic Acids Res 24, 793-794 (1996) [JCR] [WOS] |
47. | T. C. Chang, C. C. Chiang and K. Peck Hydrogen Bond Effect on the Chromophore-Oligonucleotide Conformational Structure Studied by Non-Photochemical Hole Burning Spectroscopy J Am Chem Soc 117, 7576–7577 (1995) [JCR] [WOS] |
48. | T. C. Chang, C. C. Chiang, S. H. Chou and K. Peck Temperature-Annealing-Cycling Hole Spectra of Dye and Dye-Oligonucleotide Doped in Polymer Films J Lumin 64, 75-79 (1995) [JCR] [WOS] |
49. | T. C. Chang, C. C. Chiang, S. H. Chou and K. Peck Thermally Activated Hole Filling of Dye and Dye-Oligonucleotide Doped in Polymer Films THE JOURNAL OF PHYSICAL CHEMISTRY b 99, 6620-6627 (1995) [JCR] [WOS] |
50. | L. Y. Chau, K. Peck, H. H. Yen and J. Y. Wang Agonist-induced down-regulation of platelet-activating factor receptor gene expression in U937 cells Biochem J 301, 911-916 (1994) [JCR] [WOS] |
51. | Konan Peck Single Fluorescent Molecule Detection Method Instruments Today 12(6),10-18 (1991-06) [JCR] [WOS] |