Analytical Chemistry/Biochemistry/Inorganic & Materials Chemistry/Organic Chemistry

Our laboratory focuses on developing single cell genomics and proteomics technologies with novel fluorescent probes, which will enable the systematic analysis of the identities, positions and abundances of a large number of biological molecules in individual cells. Using these approaches, we will investigate complex biological systems including cancer progression, neuronal function and stem cell differentiation. The highly interdisciplinary nature of our research program spans chemistry, biology, engineering and computer science. Detailed understanding of cancer progression, neuronal function and stem cell differentiation requires quantitative measurements of their gene expression at both transcriptional and translational levels. Due to the intrinsic heterogeneity of cancer cells, neurons and stem cells, conventional genomics and proteomics technologies carried out on pools of cells mask gene expression variations and spatial complexity of biomolecules in a population. Other single cell based methods are limited by a small number of parallel analyses, which makes them undesired to study complex gene regulatory networks. To address these issues, we will develop single cell genomics and proteomics technology to study the spatial organization of a large number of genes in the nucleus and the transcriptional and translational profiles of these genes simultaneously in single cells. With the high throughput analyzing capability, single-molecule sensitivity, and spatial preservation of molecules in cells, this approach will be used to explore the molecular mechanisms of complex diseases, identify new biomarkers, detect diseases at their early stages, and develop more effective cellular targeted therapies.

J. Guo, P. C. Hanawalt, and G. Spivak. “Comet-FISH with strand-specific probes reveals transcription-coupled repair of 8-oxoGuanine in human cells” Nucleic Acids Res, in press. J. Guo, J. Ju and N. J. Turro. “Fluorescent hybridization probes for nucleic acid detection” Anal Bioanal Chem, 2012, 402:3115-3125. S. Wang, J. Guo, T. Ono and E. T. Kool. “DNA polyfluorophores for real-time multicolor tracking of dynamic biological systems” Angew Chem Int Ed, 2012, 51:7176-7180. C. Qiu, S. Kumar, J. Guo, J. Lu, S. Shi, S. Kalachikov, J. Russo, A. Naini, E. Schon and J. Ju. “Mitochondrial SNP genotyping by MALDI-TOF mass spectrometry using cleavable biotinylated dideoxynucleotides” Anal Biochem, 2012, 427:202-210. C. Qiu, S. Kumar, J. Guo, L. Yu, W. Guo, S. Shi, J. Russo and J. Ju. “Design and synthesis of cleavable biotinylated dideoxynucleotides for DNA sequencing by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry” Anal Biochem, 2012, 427:193-201. J. Guo, S. Wang, N. Dai, Y. N. Teo and E. T. Kool. “Multispectral labeling of antibodies with polyfluorophores on a DNA backbone and application in cellular imaging” PNAS, 2011, 108: 3493-3498 N. Dai, J. Guo, Y. N. Teo and E. T. Kool. “Protease probes built from DNA: multispectral fluorescent DNA–peptide conjugates as caspase sensors” Angew Chem Int Ed, 2011, 50:5105-5109 J. Guo, L. Yu, N. J. Turro and J. Ju. “An integrated system for DNA sequencing by synthesis using novel nucleotide analogues” Acc Chem Res, 2010, 43: 551-563. L. Yu, J. Guo, N. Xu, Z. Li and J. Ju. “DNA sequencing by synthesis using novel nucleotide analogues" The Handbook of Plant Mutation Screening, 2010, 319-336. J. Guo, N. Xu, Z. Li, S. Zhang, J. Wu, D. H. Kim, M. S. Marma, Q. Meng, H. Cao, X. Li, S. Shi, L. Yu, S. Kalachikov, J. Russo, N. J. Turro and J. Ju. “Four-color DNA sequencing with 3’-O-modified nucleotide reversible terminators and chemically cleavable fluorescent dideoxynucleotides” PNAS, 2008, 105: 9145-9150 Z. Wang, X. Xu, Y. Chen, S. Zhou, N. Kong, J. Guo, H. Liu and C. Shi. “Characteristics of the ZnxMg1-xO films grown by electrophoresis method” Acta Physica Sinica, 2004, 53: 3924-3928. J. Guo, M. Gong, X. Xu, W. Zhang, H. Guo, L. Wang, Y. Chen, P. Liu and H. Liu. “The influence of anneal on the properties of SiO2 thin films prepared by sol-gel method” J Funct Mater, 2004, 35: 3171-3174.