Our laboratory focuses on the design and synthesis of novel molecular tags for biological labeling and imaging, and developing new technologies to study problems in genomics. We are pursuing these research objectives by using chemical science, engineering principles and experimental biological approaches. We have pioneered the use of chemistry and fluorescence energy transfer (ET) principles to construct ET molecular tags for high-throughput genomic research. The ET tags facilitated the rapid development of laser induced fluorescence capillary-array DNA sequencers, which are the major driving force for completion of the international Human Genome Project.
We have invented a Combinatorial Fluorescence Energy Transfer (CFET) Labeling Approach that uses a limited number of fluorescent molecules to create a maximum number of fluorescent tags that have unique fluorescence signatures. We are studying the chemical and physical properties of these CFET tags using state-of-the-art instrumentation, and applying the CFET tags to cellular imaging, multiplex DNA sequencing, genetic mutation detection, genomewide chromosome deletion and insertion analysis. We have also invented a novel DNA sequencing chemistry using solid phase capturable dideoxynucleotides and mass spectrometry. This method produces accurate and digital genetic sequence information with very high speed. We are currently developing integrated nanoscale systems to couple with the solid phase DNA sequencing chemistry for detecting disease-related mutations on a genomic scale. These technologies coupled with improvements of the conventional technologies are being implemented in large-scale genomic sequencing projects and disease gene discovery projects at the Columbia Genome Center. Two other inventions from our group involve the use of photochemistry, enzyme catalysis, mass spectrometry, and microfabrication for high throughput parallel imaging of DNA/RNA sequences in chip and nanoscale devices. These research projects are targeted to fulfill the requirement of personalized medicine We are also engaged in projects to design and synthesize novel biopolymer analogues with programmed detection and biological properties for high-throughput research in bioscience and genomics.
1. "An Integrated System for DNA Sequencing by Synthesis Using Novel Nucleotide Analogues". J. Guo, L. Yu, N.J. Turro, J. Ju. Acc. Chem. Research. 2010, 43, 551-563.
2. "Translational Control Analysis by Translationally Active RNA Capture/Microarray Analysis". K. Kudo, Y. Xi, Y. Wang, B Song, E. Chu, J. Ju, J.J. Russo, J. Ju. Nucleic Acids Research. 2010, 38: e104.
3. "Four-color DNA Sequencing with 3'-O-modified Nucleotide Reversible Terminators and Chemically Cleavable Fluorescent Dideoxynucleotides". J. Guo, N. Xu, Z. Li, S. Zhang, J. Wu, D. Kim, M. S. Marma, Q. Meng, H. Cao, X. Li, S. Shi, L. Yu, S. Kalachikov, J. Russo, N.J. Turro, J. Ju. Proceedings of the National Academy of Sciences USA. 2008, 105, 9145-9150.
4. "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.
5. "Inorganic-Organic Hybrid Luminescent Binary Probe for DNA Detection Based on Spin-Forbidden Resonance Energy Transfer" A. A. Martí, 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. "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.
7. "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.
8. "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.
9. "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.
10. "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.