Professor and Head of DNA Sequencing and Chemical Biology,
Director, Center for Genome Technology & Biomolecular Engineering
Columbia Genome Center and Department of Chemical Engineering

Columbia University
Russ Berrie Medical Science Pavilion, Room 405A
1150 St. Nicholas Avenue
New York, NY 10032

Tel: (212) 851-5172
Fax: (212) 851-5215
Email: ju@c2b2.columbia.edu

Group Members

Administrative Staff
Christine Rupp
cr314@c2b2.columbia.edu
Petra Lee Forde
pforde@c2b2.columbia.edu

Research Scientist
Jim Russo
jjr4@columbia.edu

Associate Research Scientist
Sergey Kalachikov
sk363@columbia.edu
Zengmin Li
zl79@columbia.edu
John Edwards
jre13@columbia.edu
Xiaoxu Li
lx2109@columbia.edu
Qinglin Meng
qm6@columbia.edu

Postdoctoral Research Scientist
Bindu Raveendra
br2155@columbia.edu
Angel Marti-Arbona
aam2127@columbia.edu
Dae Kim
dk2047@columbia.edu

Graduate Student
Hernan Rengifo
hrr2102@columbia.edu
Jian Wu
jw2231@columbia.edu
Jia Guo
jg2495@columbia.edu
Lin Yu
ly2141@columbia.edu

Senior Staff Associate
Shundi Shi
ss526@columbia.edu

Staff Associate
Irina Morozova
im198@columbia.edu
David Weir
dweir@columbia.edu

Techinical Support Staff
Minchen Chien
mc66@columbia.edu

Additional Links
Columbia-NIH Center of Excellence in Genomic Science

Key Words

• DNA Sequencing
• Energy Transfer Dyes
• Learning/Memory
• Mass Spectrometry
• Microarrays
• Mutation Detection
• SAGE
• Surface Chemistry

Jingyue Ju, Ph.D.

Fluorescence Imaging Chip System for Massive Parallel DNA Sequencing. The use of electrophoresis for DNA sequencing has been a major bottleneck for high-throughput DNA sequencing projects. The need for electrophoresis is eliminated when sequencing DNA by synthesis, that is, when detecting the identity of each nucleotide as it is incorporated into the growing strand of DNA in a polymerase reaction. Such a scheme, if coupled to a chip format, has the potential to markedly increase the throughput of sequencing projects. Our laboratory is developing a chip-based 'sequencing by synthesis' platform (Ju et al. United States Patent 6,664,079). This DNA sequencing system includes the construction of a chip with immobilized single-stranded DNA templates that can self-prime for the generation of the complementary DNA strand in polymerase reaction, and 4 unique fluorescently labeled nucleotide analogues with 3'-OH capped by a small chemical moiety to allow efficient incorporation into the growing strand of DNA as reversible terminators in the polymerase reaction. A 4-color fluorescence imager is then used to identify the sequence of the incorporated nucleotide on each spot of the chip. Upon removing the dye photochemically and cleaving the 3'-OH capping group, the polymerase reaction will proceed to incorporate the next nucleotide analogue and detect the next base. It is a routine procedure now to immobilize high density (>10,000 spots per chip) single-stranded DNA on a 4cm x 1cm glass chip. Thus, in the chip-based DNA sequencing system, more than 10,000 bases will be identified after each cycle and after 100 cycles million of base pairs will be generated from a single sequencing chip. This sequencing by synthesis approach can also be carried out on microbead immobilized DNA to further increase the throughput. Our laboratory, in collaboration with Professor Nicholas Turro's group in the Department of Chemistry at Columbia, published two reports in the Proceedings of the National Academy of Science in January 2003, for the first time firmly establishing the feasibility of using photocleavable fluorescent nucleotides for DNA sequencing, which is a key step to advance the field of DNA sequencing by synthesis through fluorescence imaging or by single molecule detection. Massively parallel DNA sequencing promises to bring genetic analysis to the next level where we can envision, for example, the routine comparison on individual genome profiles, a key step for personalized medicine.

Combinatorial Fluorescent Energy Transfer Tags for Multiplex Genomics Analyses. Building upon the original discoveries that led to the development of energy transfer dyes as the standards for DNA sequencing (Ju et al. Proceedings of the National Academy of Sciences USA. 1995, 92: 4347-51) that facilitated the completion of the Human Genome Project, we have developed a novel approach for constructing a large number of combinatorial fluorescence energy transfer (CFET) tags by exploiting energy transfer and combinatorial synthesis to tune the fluorescence emission signatures for multiplex genomics analysis and biological imaging (Tong et al. Nature Biotechnology, 2001, 19: 756-9). All of the CFET tags can be excited at a single wavelength and analyzed by a simple optical system. In collaboration with Dr. Russo (CGC), we are currently applying these CFET tags in multiplex DNA sequencing, single nucleotide polymorphism (SNP) detection, and genome-wide chromosome deletion and insertion analysis.

Simultaneous detection of nucleotide variations in 30 codons of the p53 gene using solid phase capturable dideoxynucleotides and mass spectrometry. Each peak represents a different polymorphism labeled with its nucleotide identity and absolute mass value. The value in parentheses, denoting the mass difference between each DNA extension product and its corresponding primer, is used to determine the nucleotide identity. A mass spectrum from a head and neck tumor containing a heterozygous genotype G/T (4684/4734 Da) (boxed) in codon 157.

High Fidelity DNA Sequencing Using Solid Phase Capturable Dideoxynucleotides and Mass Spectrometry. The current "state-of-the-art" technology for high throughput DNA sequencing relies on capillary array DNA sequencers using laser-induced fluorescence detection. While this technology addresses the throughput and read length requirements of large scale DNA sequencing projects it does not provide the high accuracy requirements of resequencing projects. Accurate resequencing, in turn, is critical for studies aimed at mutation detection, forensic identification, and serial analysis of gene expression (SAGE). Electrophoresis-based sequencing methods have inherent limitations for detecting heterozygotes and are compromised by GC compressions; mass spectrometry-based methods, on the other hand, overcome these difficulties, but fall short of the throughput and read length requirements. A fundamental precondition for using mass spectrometry for de novo sequencing, and not merely for single base change (SNP) substitution, is that DNA sequencing fragments must be stringently pure and free of salts, false terminations, and other contaminants before being introduced into the detector. We are developing an approach that relies on the high affinity between biotin and streptavidin to remove undesired components in the sequencing reaction: DNA sequencing fragments are generated using biotinylated dideoxynucleotides and then captured at the 3' end by a streptavidin-coated solid phase. The captured DNA fragments are then chemically or photo-cleaved from the solid phase and loaded on a matrix assisted laser desorption/ionization time of flight (MALDI-TOF) mass spectrometer. By mass-tagging the dideoxynucleotides with aromatic functionalities, mass separation of the DNA sequencing fragments is dramatically enhanced to increase resolution and read length. We are also developing a porous-channel based, affinity-capture and light directed-release system for continuous online generation of pure DNA sequencing fragments using solid phase capturable dideoxynucleotides for analysis by MALDI-TOF mass spectrometer.

Genome Analysis of Model Organism. As a leading laboratory for the Columbia-NIH Center of Excellence in Genomic Science, we are conducting research to develop novel genomic technologies and cellular imaging approaches that will allow (1) a genome to be sequenced on a chip, (2) gene expression to be measured in single cells, and (3) gene transcripts and their movement in single cells to be detected in real-time. The technologies will be implemented to study genes and their functions in neurons related to learning and memory and to explore how genes regulate behavior. Dr. Eric Kandel and colleagues have pioneered the molecular neurobiological study of learning and memory (for which Dr. Kandel received the 2000 Nobel Prize in Medicine) largely based upon their studies of the sea slug, Aplysia, an organism with unique advantages for neuroscience research. We have formed a unique collaboration with Dr. Kandel and Dr. Leonid Moroz at the University of Florida to construct and sequence representative cDNA libraries from the Aplysia central nervous system. Our laboratory is sequencing and analyzing the full-length Aplysia cDNAs and is measuring the gene expression in the Aplysia nervous system for the study of molecular basis of learning and memory.

Publications

1. "3'-O-Modified Nucleotides as Reversible Terminators for Pyrosequencing". J. Wu, S. Zhang, Q. Meng, H. Cao, Z. Li, X. Li, S. Shi, D. Kim, N.J. Turro, J. Ju. Proceedings of the National Academy of Sciences USA. 2007, 104, 16462-16467.
2. "An Integrated System for DNA Sequencing by Synthesis" in New High Throughput Technologies for DNA Sequencing and Genomics, Perspectives in Bioanalysis. J. Edwards, D. Kim, J. Ju. (Editor. Keith Mitchelson) Elsevier, 2007, 2, 187-205.
3. "A Mammalian microRNA Expression Atlas Based on Small RNA Library Sequencing". P. Landgraf, M. Rusu, R. Sheridan, A. Sewer, N. Iovino, A. Aravin, S. Pfeffer, A. Rice, A.O. Kamphorst, M. Landthaler, C. Lin, N.D. Socci, L. Hermida, V. Fulci, S. Chiaretti, R. Foa, J. Schliwka, U. Fuchs, A. Novosel, R.U. Muller, B. Schermer, U. Bissels, J. Inman, Q. Phan, M. Chien, D.B. Weir, R. Choksi, G. De Vita, D. Frezzetti, H.I. Trompeter, V. Hornung, G. Teng, G. Hartmann, M. Palkovits, R. Di Lauro, P. Wernet, G. Macino, C.E. Rogler, J.W. Nagle, J. Ju, F.N. Papavasiliou, T. Benzing, P. Lichter, W. Tam, M.J. Brownstein, A. Bosio, A. Borkhardt , J.J. Russo, C. Sander, M. Zavolan, T. Tuschl. Cell. 2007, 129, 1401-1414.
4. "Cellular Cofactors Affecting Hepatitis C Virus Infection and Replication". G. Randall, M. Panis, J.D. Cooper, T.L. Tellinghuisen, K.E. Sukhodolets, S. Pfeffer, M. Landthaler, P. Landgraf, S. Kan, B.D. Lindenbach, M. Chien, D.B. Weir, J.J. Russo, J. Ju, M.J. Brownstein, R. Sheridan, C. Sander, M. Zavolan, T. Tuschl, C.M. Rice. Proceedings of the National Academy of Sciences USA. 2007, 104, 12884-12889.
5. "Inorganic-Organic Hybrid Luminescent Binary Probe for DNA Detection Based on Spin-Forbidden Resonance Energy Transfer" A. A. Marti, C. Puckett, J. Dyer, N. Stevens, S. Jockusch, J. Ju, J. K. Barton, N. J. Turro. J. Am. Chem. Soc. 2007, 129, 8680-8681.
6. "Design and Characterization of Two-dye and Three-dye Binary Fluorescent Probes for mRNA Detection". A. A. MartíX. Li, S. Jockusch, N. Stevens, Z. Li, B. Raveendra, S. Kalachikov, I. Morozova, J. J. Russo, D. L. Akins, J. Ju, N. J. Turro. Tetrahedron, 2007, 63, 3591-3600.
7. "Fluorescent Hybridization Probes for Sensitive and Selective DNA and RNA Detection". A. A. MartíS. Jockusch, N. Stevens, J. Ju, N. J. Turro. Acc. Chem. Res. 2007, 40, 402-409.
8. "Quantitative Technologies Establish a Novel microRNA Profile of Chronic Lymphocytic Leukemia". V. Fulci, S. Chiaretti, M. Goldoni, G. Azzalin, N. Carucci, S. Tavolaro, L. Castellano, A. Magrelli, F. Citarella, M. Messina, R. Maggio, N. Peragine, S. Santangelo, F.R. Mauro, P. Landgraf, T. Tuschl, D.B. Weir, M. Chien, J.J. Russo, J. Ju, R. Sheridan, C. Sander, M. Zavolan, A. Guarini, R. Foa, G. Macino. Blood. 2007, 109, 4944-4951.
9. "Four-Color DNA Sequencing by Synthesis Using Cleavable Fluorescent Nucleotide Reversible Terminators". J. Ju, D. Kim, L. Bi, Q. Meng, X. Bai, Z. Li, X. Li, M.S. Marma, S. Shi, J. Wu, J.R. Edwards, A. Romu, N.J. Turro. Proceedings of the National Academy of Sciences USA. 2006, 103, 19635-19640.
10. "Neuronal Transcriptome of Aplysia: Neuronal Compartments and Circuitry". L.L. Moroz, J.R. Edwards, S.V. Puthanveettil, A. Kohn , T. Ha, A. Heyland, B. Kudsen, A. Sahni , F. Yu, L. Liu, S. Jezzini, R. Sadreyev, P. Lovell, W. Iannucculli, M. Chen, T. Nguyen, H. Sheng, R. Shaw, S. Kalachikov, Y. Panchin, W. Farmerie, J.J. Russo, J. Ju, E.R. Kandel. Cell. 2006, 127, 1453-1467.
11. "Design and Synthesis of a Chemically Cleavable Fluorescent Nucleotide 3'-O-Allyl-dGTP-allyl-Bodipy-FL-510 as a Reversible Terminator for DNA Sequencing by Synthesis". L. Bi, D. H. Kim, J. Ju. J. Am. Chem. Soc. 2006, 128, 2542-2543.
12. "Combinatorial Fluorescence Energy Transfer Molecular Beacons for Probing Nucleic Acid Sequences". X. Li, Z. Li, A. Marti, S. Jockusch, N. Stevens, D.L. Akins, N.J. Turro, J. Ju. Photochemical & Photobiological Sciences. 2006, 5, 896-902.
13. "Design and Synthesis of a Photocleavable Fluorescent Nucleotide 3'-O-Allyl-dGTP-PC-Bodipy-FL-510 as a Reversible Terminator for DNA Sequencing by Synthesis". Q. Meng, D.H. Kim, X. Bai, L. Bi, N.J. Turro, J. Ju. J. Org. Chem. 2006, 71, 3248-3252.
14. "Pyrene Binary Probes for Unambiguous Detection of mRNA Using Time-Resolved Fluorescence Spectroscopy" A. Marti, X. Li, S. Jockusch, Z. Li, B. Raveendra, S. Kalachikov, J. Russo, I. Morozova, S. Puthanveettil, J. Ju, N.J. Turro. Nucleic Acids Research. 2006, 34, 3161-3168.
15. "Molecular Beacons with Intrinsically Fluorescent Nucleotides". A. Marti, S. Jockusch, Z. Li, J. Ju, N.J. Turro. Nucleic Acids Research. 2006, 34, e50.
16. "The Large-Scale Structure of Genomic Methylation Patterns" R.A. Rollins, F.G. Haghighi, J.R. Edwards, J. Ju & T.H. Bestor. Genome Research. 2006, 16, 157-163.
17. "Computational Prediction of DNA Methylationn Landscape in the Human Genome". R. Das, N. Dimitrova, Z.Y. Xuan, R.A. Rollins, F.G. Haghighi, J.R. Edwards, J. Ju , T.H. Bestor, and M.Q. Zhang. Proceedings of the National Academy of Sciences USA. 2006, 103, 10713-10716.
18. "A Novel Class of Small RNAs Bind to MILI Protein in Mouse Testes". Aravin, D. Gaidatzis, S. Pfeffer, M. Quintana, P. Morris, S. Kuramochi-Miyagawa, T. Nakano, M. Chien, J.J. Russo, J. Ju, R. Sheridan, C. Sander, M. Zavolan & T. Tuschl. Nature. 2006, 442, 203-207.
19. "Spectroscopic Investigation of a FRET Molecular Beacon Containing Two Fluorophores for Probing DNA/RNA Sequences". S. Jockusch, A. Marti, N.J. Turro, Z. Li, X. Li, J. Ju, N. Stevens, and D. L. Akins. Photochemical & Photobiological Sciences. 2006, 5, 493-498.
20. "MassTag Polymerase Chain Reaction Detection of Respiratory Pathogens, Including A New Rhinovirus Genotype, that Caused Influenza-Like Illness in New York State During 2004-2005". D. Lamson, N. Renwick, V. Kapoor, Z. Liu, G. Palacios, J. Ju, A. Dean, K. St George, T. Briese, W.I. Lipkin. Journal of Infectious Diseases. 2006, 194, 1398-1402
21. "MassTag Polymerase Chain Reaction for Differential Diagnosis of Viral Hemorrhagic Fevers". G. Palacios, T. Briese, V. Kapoor, O. Jabado, Z. Liu, M. Venter, J. Zhai, N. Renwick, A. Grolla, T. W. Geisbert, C. Drosten, J. Towner, J. Ju, J. Paweska, S. Nichol, R. Swanepoel, H. Feldmann, P. Jahrling, W.I. Lipkin. Emerging Infectious Diseases. 2006, 12, 692-695.
22. "Multiplex Single Nucleotide Polymorphism Detection by Combinatorial Fluorescence Energy Transfer Tags and Molecular Affinity" A.K. Tong, J. Ju. Methods in Molecular Biology. 2006, 335, 201-214.
23. "Prognostic Values of microRNAs in Colorectal Cancer". X. Yaguang, A. Formentini, M. Chien, D.B. Weir, J.J. Russo, J. Ju, M. Kornmann and J. Ju. Biomarker Insights. 2006, 2, 113.121.
24. "Four-Color DNA Sequencing by Synthesis on Chip Using Photocleavable Fluorescent Nucleotide Analogues". T. S. Seo, X. Bai, D. H. Kim, Q. Meng, S. Shi, H. Ruparel, Z. Li, N.J. Turro & J. Ju. Proceedings of the National Academy of Sciences USA. 2005, 102, 5926-5931.
25. "Design and Synthesis of a 3'-O-Allyl Photocleavable Fluorescent Nucleotide as a Reversible Terminator for DNA Sequencing By Synthesis". H. Ruparel, L, Bi, Z. Li, X. Bai, D. H. Kim, N.J. Turro & J. Ju. Proceedings of the National Academy of Sciences USA. 2005, 102, 5932-5937.
26. "Mass Spectrometry DNA Sequencing" J. R. Edwards, H. Ruparel, J. Ju. Mutation Research. 2005, 573, 3-12.
27. "Molecular Engineering Approaches for DNA Sequencing and Analysis". X. Bai, J.R. Edwards, & J. Ju. Expert Review of Molecular Diagnostics. 2005, 5, 797-808.
28. "Two-Photon Excitation Induced Fluorescence of a Tri-fluorophore Labeled DNA" S. Jockusch, Z. Li, J. Ju & N.J. Turro. Photochemistry and Photobiology. 2005, 81, 238-241.
29. "The Developmental miRNA Profiles of Zebrafish as Determined by Small RNA Cloning". P.Y. Chen, H. Manninga, K. Slanchev, M. Chien, J.J. Russo, J. Ju, R. Sheridan, C. Sander, M. Zavolan & T. Tuschl. Genes and Development. 2005, 11, 1288-1293.
30. "Identification of microRNAs of the Herpesvirus Family". S. Pfeffer, A. Sewer, M. Lagos-Quintana, R. Sheridan, C. Sander, F.A. Grasser, L.F. van Dyk, C.K. Ho, S. Shuman, M. Chien, J.J. Russo, J. Ju, G. Randall, B.D. Lindenbach, C.M. Rice, V. Simon, D D. Ho, M. Zavolan & T. Tuschl. Nature Methods. 2005, 2, 269-276.
31. "Diagnostic System for Rapid and Sensitive Differential Detection of Pathogens". T. Briese, G. Palacios, M. Kokoris, O, Jabado, Z. Liu, N. Renwick, V. Kapoor, I. Casas, F. Pozo, R. Limberger, P. Perez-Brena, J. Ju, W.I. Lipkin. Emerging Infectious Diseases. 2005, 11, 310-313.
32. "Identification of Virus-Encoded microRNAs". S. Pfeffer, M. Zavolan, F.A. Grasser, M. Chien, J.J. Russo, J. Ju, B. John, A.J. Enright, D. Marks, C. Sander and T. Tuschl. Science. 2004, 304, 734-736.
33. "Photocleavable Fluorescent Nucleotides for DNA Sequencing on a Chip Constructed by Site-Specific Coupling Chemistry". T.S. Seo, X. Bai, Z. Li, H. Ruparel, N.J. Turro & J. Ju. Proceedings of the National Academy of Sciences USA. 2004, 101, 5488-5493.
34. "Thirty Fold Multiplex Genotyping of p53 Gene Using Solid Phase Capturable Dideoxynucleotides and Mass Spectrometry". S. Kim, M. Ulz, T. Nguyen, C. Li, B. Tycko, and J. Ju. Genomics. 2004, 83, 924-931.
35. "Digital Detection of Genetic Mutations Using SPC-Sequencing" H. Ruparel, M. E. Ulz, S. Kim, and J. Ju. Genome Research. 2004, 14, 296-300.
36. "Design and Synthesis of a Photocleavable Biotinylated Nucleotide for DNA Analysis by Mass Spectrometry" X. Bai, S. Kim, Z. Li, N.J. Turro & J. Ju. Nucleic Acids Research. 2004, 32, 535-541
37. "1,3-Dipolar Cycloaddition of Azides with Electron-deficient Alkynes Under Mild Condition in Water". Z. Li, T. S. Seo, J. Ju. Tetrahedron Letters. 2004, 45, 3143-3146.
38. "The Genomic Sequence of the Accidental Pathogen Legionella Pneumophila". M. Chien, I. Morozova, S. Shi, H. Sheng, J. Chen, S.M. Gomez, G. Asamani, K. Hill, J. Nuara, M. Feder, J. Rineer, J.J. Greenberg, V. Steshenko, S.H. Park, B. Zhao, E. Teplitskaya, J.R. Edwards, S. Pampou, A. Georghiou, I.C. Chou, W. Iannuccilli, M.E. Ulz, D.H. Kim, A. Geringer-Sameth, C. Goldsberry, P. Morozov, S.G. Fischer, G. Segal, X. Qu, A. Rzhetsky, P. Zhang, E. Cayanis, P.J. De Jong, J. Ju, S. Kalachikov, H.A. Shuman, J.J. Russo. Science. 2004, 305, 1966-1968.
39. "A Photocleavable Fluorescent Nucleotide for DNA Sequencing and Analysis". Z. Li, X. Bai, H. Ruparel, S. Kim, N.J. Turro & J. Ju. Proceedings of the National Academy of Sciences USA. 2003, 100, 414-419.
40. "Digital Genotyping Using Molecular Affinity and Mass Spectrometry" S. Kim, H.D. Ruparel, T.C. Gilliam, and J. Ju. Nature Reviews Genetics. 2003, 4, 1001-1008.
41. "Photocleavage of a 2-Nitrobenzyl Linker Bridging a Fluorophore to the 5' End of DNA". X . Bai, Z. Li, S. Jockusch, N.J. Turro & J. Ju. Proceedings of the National Academy of Sciences USA. 2003, 100, 409-413.
42. "Multiplex Genotyping of the Human .2-Adrenergic Receptor Gene Using Solid Phase Capturable Dideoxynucleotides and Mass Spectrometry". S. Kim, S. Shi, T. Bonome, J. R. Edwards, J. Russo, and J. Ju. Analytical Biochemistry. 2003, 316, 251-258
43. "Site-Specific Fluorescent Labeling of DNA Using Staudinger Ligation". T.S. Seo, C. Wang, Z. Li, H. Ruparel, and J. Ju. Bioconjugate Chemistry. 2003, 14, 697-701
44. "Identification of Critical Residues in a Class C .-Lactamase Using Combinatorial Scanning Mutagenesis". S. D. Goldberg, W. Iannuccilli, T. Nguyen, J. Ju, and V.W. Cornish. Protein Science. 2003, 12, 1633-1645.
45. "Solid Phase Capturable Dideoxynucleotides for Multiplex Genotyping Using Mass Spectrometry" S. Kim, J. R. Edwards, L. Deng, W. Chung, and J. Ju. Nucleic Acids Research. 2002, 30, e78 (p1-6).
46. "Click Chemistry to Construct Fluorescent Oligonucleotides for DNA Sequencing" T.S. Seo, Z. Li, H. Ruparel, and J. Ju. Journal of Organic Chemistry. 2002, 68, 609-612.
47. "Single-nucleotide Polymorphism Detection by Combinatorial Fluorescence Energy Transfer Tags and Biotinylated Dideoxynucleotides". A.K. Tong, & J. Ju. Nucleic Acids Research. 2002, 30, e19 (p1-7).
48. "Synthesis of Oligodeoxyribonucleoside Phosphorothioates Using Lawesson's Reagent for the Sulfur Transfer Step" J. Ju. & C. McKenna, Bioorganic & Medicinal Chemistry Letters. 2002, 12, 1643-1645.
49. "DNA Sequencing with Solid Phase Capturable Dideoxynucleotides and Energy Transfer Primers" J. Ju. Analytical Biochemistry. 2002, 309, 35-39.
50. "Combinatorial Fluorescence Energy Transfer Tags: New Molecular Tools for Genomics Applications". A.K. Tong, Z. Li, J. Ju. Journal of Quantum Electronics Special Issue for Biomedical Applications. 2002, 38, 110-121.
51. "Fluorescence Energy Transfer Reagents for DNA Sequencing and Analysis" in Structure and Dynamics of Confined Spaces (NATO Science Series, High Technology) J. Ju. 2002, 87, 371-383. eds. J.J. Kasianowicz, M.S.Z. Kellermayer, and D.W. Deamer (Kluwer Academic Publishers, Netherlands).
52. "Combinatorial Fluorescence Energy Transfer Tags for Multiplex Biological Assays" A.K. Tong, Z. Li, G.S. Jones, J J. Russo, J. Ju. Nature Biotechnology. 2001, 19, 756-759.
53. "DNA Sequencing Using Biotinylated Dideoxynucleotides and Mass Spectrometry" J.R. Edwards, Y. Itagaki and J. Ju. Nucleic Acids Research. 2001, 29, e104 (p1-6).
54. "Triple Fluorescence Energy Transfer in Covalently Tri-Chromophore-Labeled DNA" A. Tong, S. Jockusch, Z. Li, H-R. Zhu, D. Akins, N. J. Turro, and J. Ju. J. Am. Chem. Soc. 2001, 123, 12923-12924.
55. "DNA Sequencing" in Short Protocols in Molecular Biology, 4th Ed". B.E. Slatko, L.M. Albright, S. Tabor and J. Ju. (1999) eds. Ausubel, F.M. et al. (John Wiley & Sons, Inc, New York and London), pp. 7-25 to 7-37. (Book Chapter).
56. "Energy Transfer Fluorescent Primers: State-of-the-art in High-throughput DNA Sequencing" J. Ju, A.N. Glazer and R.A. Mathies. Genome Digest, 1997, 8-9.
57. "Cassette Labeling for Facile Construction of Energy Transfer Fluorescent Primers" J. Ju, A.N. Glazer and R.A. Mathies. Nucleic Acids Research, 1996, 24, 1144-1148.
58. "Energy Transfer Primers: A New Fluorescence Labeling Paradigm for DNA Sequencing and Analysis" J. Ju, A.N. Glazer and R.A. Mathies. Nature Medicine, 1996, 2, 246-249.
59. "DNA Sequencing Using a Four-Color Confocal Fluorescence Capillary Array Scanner" I. Kheterpal, J. Scherer, S. M. Clark, A. Radhakrishnan, J. Ju, C. L. Ginther, G. F. Sensabaugh and R. A. Mathies. Electrophoresis, 1996, 17, 1852-1859.
60. "High-Resolution Capillary Array Electrophoretic Sizing of Multiplexed Short Tandem Repeat Loci Using Energy-Transfer Fluorescent Primers" Y. Wang, J.M. Wallin, J, Ju, G.F. Sensabaugh and R.A. Mathies. Electrophoresis, 1996, 17, 1485-1490.
61. "Cyanine Dyes with High Absorption Cross Section as Donor Chromophores in Energy Transfer Primers" S.C. Hung, J. Ju, A.N. Glazer and R.A. Mathies. Analytical Biochemistry, 1996, 243, 15-27.
62. "Energy Transfer Primers with 5- or 6-Carboxyrhodamine-6G as Acceptor Chromophores " S.C. Hung, J. Ju, A.N. Glazer and R.A. Mathies. Analytical Biochemistry, 1996, 238, 165-70.
63. "Energy Transfer Fluorescent Dye-Labeled Primers for DNA Sequencing and Analysis" J. Ju, C. Ruan, C.W. Fuller, A.N. Glazer and R.A. Mathies. Proc. Natl. Acad. Sci. U.S.A. 1995, 92, 4347-4351.
64. "Design and Synthesis of Energy Transfer Fluorescent Dye-Labeled Oligonucleotide Primers and Their Application for DNA Sequencing and Analysis " J. Ju, I. Kheterpal, J. Scherer, C. Ruan, C. Fuller, A.N. Glazer and R.A. Mathies. Analytical Biochemistry, 1995, 231, 131-140.
65. "Rapid Sizing of Short Tandem Repeat Alleles Using Energy Transfer Fluorescent Primers and Capillary Array Electrophoresis" Y. Wang, J. Ju, B.A. Carpenter, J.M. Atherton, R.A. Mathies and G.F. Sensabaugh. Anal. Chem. 1995, 67, 1197.
66. "Troika Acids: Synthesis, Structure and Fragmentation Pathways of Novel a-(Hydroxyimino)-Phosphonoacetic Acids" B.A. Kashemirov, J. Ju, R. Bau and C.E. McKenna. J. Am. Chem. Soc. 1995, 117, 7285-7286.
67. "Some Phosphonic Acid Analogs as Inhibitors of Pyrophosphate-dependent Phospho-fructokinase, A Novel Target in Toxoplasma Gondii" Z. Peng, J.M. Mansour, F. Araujo, J. Ju, C.E. McKenna and T.E. Mansour, Biochemical Pharmacology 1995, 49, 105-113.
68. "E/Z Stereoisomer Assignment by 13C NMR in Trifunctional Phosphonate a-Oximes and a-Arylhydrazones" C.E. McKenna, B.A. Kashemirov, J. Ju. J. Chem. Soc. Chem. Commun., 1994, 1211-1212.
69. "Synthesis and HIV-1 Reverse Transcriptase Inhibition Activity of Functionalized Pyrophosphate Analogues" C.E. McKenna, A. Khare, J. Ju, Z. Li, G. Duncan, Y. Cheng and R. Kilkuskie. Phosphorus Sulfur. 1993, 76, 139-142.
70. "Simple and Conjugate Bifunctional Thiophosphonates: Synthesis and Potential as Anti-Viral Agents" C.E. McKenna, Z. Li, J. Ju, P.T. Pham, R. Kilkuskie, T.L. Loo and J. Straw. Phosphorus Sulfur. 1993, 74, 469-470.
71. "Stereoselective Aldol Coupling of Cobalt-Complexed Alkynyl Aldehydes." J. Ju, B.R. Reddy, M. Khan and K.M. Nicholas. Journal of Organic Chemistry, 1989, 54, 5426-5428.

Patents

1. United States Patent 7,074,597, (2006) J. Ju "Multiplex Genotyping Using Solid Phase Capturable Dideoxynucleotides and Mass Spectrometry".
2. United States Patent 7,015,000, (2006) R.A. Mathies, A.N. Glazer and J. Ju "Probes Labeled with Energy Transfer Coupled Dyes".
3. United States Patent 6,664,079, (2003) J. Ju, Z. Li, J.R. Edwards and Y. Itagaki "Massive Parallel Method for Decoding DNA and RNA".
4. United States Patent 6,627,748, (2003) J. Ju, Z. Li, A. Tong and J. Russo "Combinatorial Fluorescence Energy Transfer Tags and their Applications for Multiplex Genetic Analyses".
5. United States Patent 6,544,744, (2003) R.A. Mathies, A.N. Glazer and J. Ju "Probes Labeled with Energy Transfer Coupled Dyes".
6. United States Patent 6,177,247, (2001) R.A. Mathies, A.N. Glazer and J. Ju "Detection Methods Using Probes Labeled with Energy Transfer Coupled Dyes for DNA Fragment Analysis".
7. United States Patent 6,046,005, (2000) J. Ju, K, Konrad "Nucleic Acid Sequencing with Solid Phase Capturable Terminators Comprising a Cleavable Linking Group".
8. United States Patent 6,150,107, (2000) A.N. Glazer, R.A. Mathies, S-C. Hung, and J. Ju "Methods of Sequencing and Detection Using Energy Transfer Labels with Cyanine Dyes as Donor Chromophores".
9. United States Patent 6,028,190, (2000) R.A. Mathies, A.N. Glazer and J. Ju "Probes Labeled with Energy Transfer Coupled Dyes".
10. United States Patent 5,876,936, (1999) J. Ju "Nucleic Acid Sequencing with Solid Phase Capturable Terminators".
11. United States Patent 5,952,180, (1999) J. Ju "Sets of Energy Transfer Fluorescent Tags and Their Use in Multi-Component Analysis ".
12. United States Patent 5,869,255, (1999) R.A. Mathies, A.N. Glazer and J. Ju "Probes Labeled With Energy Transfer Coupled Dyes Exemplified with DNA Fragment Analysis".
13. United States Patent 5,804,386, (1998) J. Ju "Sets of Energy Transfer Fluorescent Tags and Their Use in Multi-Component Analysis ".
14. United States Patent 5,707,804, (1998) R.A. Mathies, A.N. Glazer and J. Ju "Primers Labeled with Energy Transfer Coupled Dyes for DNA Sequencing".
15. United States Patent 5,728,528, (1998) R.A. Mathies, A.N. Glazer and J. Ju "Universal Spacer/Energy Transfer Dyes".
16. United States Patent 5,853,992, (1998) A.N. Glazer, S-C. Hung, R.A. Mathies, and J. Ju "Cyanine Dyes with High Absorption Cross Section as Donor Chromophores in Energy Transfer Primers".
17. United States Patent 5,814,454, (1998) J. Ju "Sets of Energy Transfer Fluorescent Tags and Their Use in Multi-Component Analysis ".
18. United States Patent 5,654,419, (1997) R.A. Mathies, A.N. Glazer and J. Ju "Fluorescent Labels and Their Use in Separations".
19. United States Patent 5,688,648, (1997) R.A. Mathies, A.N. Glazer and J. Ju "Probes Labeled with Energy Transfer Coupled Dyes".

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