California NanoSystems Institute

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People

James Liao, Ph.D.

Professor, Chemical and Biomolecular Engineering

Member, NanoBiotechnology and Biomaterials, California NanoSystems Institute

Education:

Degrees:

Ph.D., University of Wisconsin, Madison, 1987

Honors and Awards:

2006 American Institute of Chemical Engineers, Food, Phamaceutical, and Bioengineering Division Award
2006 California Institute of Technology, W.N. Lacey Lectureship
2002 Fellow of American Institute for Medical and Biological Engineering
1992 NSF Presidential Young Investigator Award

Contact Information:

Email Address:	liaoj@seas.ucla.edu
Work Email Address:	liaoj@ucla.edu

Work Address:	Office Boelter Hall, 159210 Los Angeles, CA 90095 UNITED STATES

Home Page:	http://www.seas.ucla.edu/~liaoj/

Work Phone Number:	51656 Office

Research Interests:

We develop novel technologies for metabolic genomics research in microbial and human systems. Our research integrates molecular biology and chip-based technologies to investigate molecular recognition, signal amplification, and biological regulation.

Understanding how genes and proteins work at the genomic scale is essential for biomedical research and applications. Most commonly, the function and regulation of genes are studied one at a time, with tedious and time-consuming methods. Genomic technologies, such as DNA microarrays (or gene chips), have accelerated this process significantly. With the proper DNA probes, this technology allows the detection of mRNA levels at the genomic scale. This technology is coupled with large scale molecular cloning, directed evolution, and mass spectrometry to probe the biochemical activities in the cell. Specifically, we use these techniques to identify genes in new pathways, to determine roles of unknown genes, to uncover new roles of known genes, and to define the genetic control loops in the cell. In addition, the principles of biomolecular recognition and signal amplification in biological systems are used to design chip-based technologies for the high-throughput processing of biological samples. Meanwhile, mathematical and statistical tools are being developed for analyzing the large amount of data generated.

Technical Research Interest:

Professor Liao and his research group are focusing on elucidating and reconstructing biological regulatory networks at the systems level. Experimental and computational methods are being developed to understand, predict, and redesign cellular behavior. An integrative technique called Network Component Analysis (NCA) have been developed which utilizes mRNA expression and transcriptional network connectivity to determine network component dynamics, functions, and interactions. This approach has been applied to elucidate transcription factor dynamics in Saccharomyces cerevisiae cell-cycle regulation, detect cross-talks in Escherichia coli two component signaling pathways, and characterize E. coli carbon source transition. In addition, novel synthetic gene-metabolic circuits have been designed and constructed to demonstrate system-wide understanding of cellular regulation. To this end, artificial feedback regulation, cell-cell communication, and oscillatory circuits have been constructed, which demonstrate the design principles of gene-metabolic regulation in the cell.

Selected Publications:

Brynildsen, M. P. Liao, J. C. , An integrated network approach identifies the isobutanol response network of Escherichia coli, Mol Syst Biol, 2009, 5, 277.

Contador, C. A. Rizk, M. L. Asenjo, J. A. Liao, J. C. , Ensemble modeling for strain development of l-lysine-producing Escherichia coli, Metab Eng, 2009.

Connor, M. R. Liao, J. C. , Microbial production of advanced transportation fuels in non-natural hosts, Curr Opin Biotechnol, 2009.

Shota Atsumi, Taizo Hanai & James C. Liao, Non-fermentative pathways for synthesis of branched-chain higher alcohols as biofuels, Nature, 2008, 451, 86-89.

Brynildsen, M.P.; Wu, T.Y.; Jang, S.S. and Liao, J.C., Biological Network Mapping and Source Signal Deduction, Bioinformatics, 2007, 23, 1775-1782.

Watanabe, J.; K.J. Chou, J. C. Liao, Y. Miao, H. Meng, H. Ge, V. Grijalva, K. Kozak, J. P. Whitelegge, T. D. Lee, R. Farias-Eisner, M. Navab, A. M. Fogelman, S.T. Reddy , Differential Association of Hemoglobin with Pro-Inflammatory High Density Lipoproteins in Atherogenic/Hyperlipidemic Mice �� A Novel Biomarker of Atherosclerosis, J. Biol. Chem., 2007, 282 (32), 23698-707.

Bernstein, J.R.; Bulter, T.; Shen, C.R. and Liao, J.C. , Directed Evolution of Ribosomal Protein S1 for Enhanced Translational Efficiency of High GC Rhodopseudomonas palustris DNA in Escherichia coli,, J. Biol. Chem. , 2007, 282 (26), 18929-36.

Ohta, A.T., P.Y. Chiou, T.H. Han, J.C. Liao, U. Bhardwaj, E.R.B. McCabe, F.Yu, R. Sun, and M.C. Wu , Dynamic cell and microparticle control via optoelectronic tweezers, J. Microelectromechanical Systems, 2007, 16, 491-499.

Hanai, T.; S. Atsumi; J. C. Liao , Engineered synthetic pathway for isopropanol production in Escherichia coli, Appl. Env. Microbiol., 2007, Accepted.

Sriram, G.; L. Rahib; J.S. He; A.E.Campos; L. S Parr; J.C. Liao; K.M. Dipple, Global Metabolic Effects of Glycerol Kinase Overexpression in Rat Hepatoma Cells, Molecular Genetics and Metabolism, 2007, In Print.

Hyduke, D.R.; Jarboe, L.R.; Tran, L.M.; Chou, K.J.Y.; Liao, J.C., Integrated Network Analysis Identifies Nitric Oxide Response Networks and dihydroxyacid dehydratase as a Crucial Target in Escherichia coli, Proc. Natl. Acad. Sci. USA, 2007, 104, 8484-8489.

Atsumi, S.; A. F. Cann; M. Connor; C.R. Shen; K. M. Smith; M.P. Brynildsen; K.J.Y. Chou; T. Hanai, and J. C. Liao, Metabolic engineering of Escherichia coli for 1-butanol Production, Metabolic Eng., 2007, In Print.

Han, T. H.; Perloff, J.K.; and Liao, J.C., Nitric Oxide Metabolism in Adults with Cyanotic Congenital Heart Disease, Am. J. Cardiology, 2007, 99, 691-5.

Han, T. H. Perloff, J. K. Liao, J. C. , Nitric oxide metabolism in adults with cyanotic congenital heart disease, Am J Cardiol, 2007, 99 (5), 691-5.

Wong, W.W., T.Y. Tsai, J.C. Liao , Single-cell zeroth-order protein degradation enhances the robustness of synthetic oscillator, Mol. Systems. Biol., 2007, 3, 130.

Rahib, L., MacLennan, N.K., Horvath, S., Liao, J.C., and Dipple, K.M, lycerol Kinase Deficiency Alters Expression of Genes Involved in Lipid Metabolism, Carbohydrate Metabolism, and Insulin Signaling, G. Eur. J. Hum. Genet. , 2007, 15, 646-657.

Brynildsen, M. P. Tran, L. M. Liao, J. C. , A Gibbs sampler for the identification of gene expression and network connectivity consistency, Bioinformatics, 2006, 22 (24), 3040-6.

Oh, MK; Cha, MJ; Lee, SG; Rohlin, L and Liao, JC., Dynamic gene expression profiling of Escherichia coli in carbon source transition from glucose to acetate, J. Microbiol. Biotechnol., 2006, 16 (4), 543-549.

Liao, J.C. , Systems Biology: Where does chemical engineering stand? , J. Chin. Inst. Chem. Eng. in print. (invited paper) , 2006, 103-106.

MacLennan, N.K., Rahib, L., Shin, C., Fang, Z., Horvath, S., Dean J., Liao, J.C., McCabe, E.R.B. and Dipple, K.M., Targeted Disruption of Glycerol Kinase Gene In Mice: Expression Analysis in Liver Shows Alterations in Network Partners Related to Glycerol Kinase Activity, Human Molec. Genet. , 2006, 15 (3), 405-415.

Wong, WW and Liao, JC., The design of intracellular oscillators that interact with metabolism, Cell. Mol. Life Sci., 2006, 1215-1220.

Galbraith, S.J.; Tran, L.M. and Liao, J.C., Transcriptome Network Component Analysis with Limited Microarray Data, Bioinformatics, Accepted , 2006.

Brynildsen, M.P., Tran, L. M. and Liao, J.C., Versatility and Connectivity Efficiency of Bipartite Transcription Networks, Biophysical Journal, Accepted, 2006.

Boscolo, R.; Sabatti, C.; Liao, J.C. and Roychowdhury, V.P., A Generalized Framework for Network Component Analysis, IEEE Trans. Comp. Biol. Bioinfomatics , 2005, 2, 289-301.

Kao, K.C; Tran, L.M.; Liao, J.C., A global regulatory role of gluconeogenic genes in Escherichia coli revealed by transcriptome network analysis, J. Biol. Chem. , 2005, 280, 36079-36087.

Fung, E.; Wong, W.W.; Suen, J.K.; Bulter, T.; Lee, S.G.; and Liao, J.C., A synthetic gene-metabolic oscillator, Nature, 2005, 435, 118-122.

Hyduke, D. R. Liao, J. C. , Analysis of nitric oxide donor effectiveness in resistance vessels, Am J Physiol Heart Circ Physiol, 2005, 288 (5), H2390-9.

Yang, Y.L. and Liao, J.C., Determination of functional interactions among signalling pathways in Escherichia coli K-12, Metabolic Engineering, 2005, 7 , 280-290.

Han, T. H. Pelling, A. Jeon, T. J. Gimzewski, J. K. Liao, J. C. , Erythrocyte nitric oxide transport reduced by a submembrane cytoskeletal barrier, Biochim Biophys Acta, 2005, 1723 (1-3), 135-42.

Han, T.H.; Pelling, A; Jeon, T.J.; Gimzewski, J.K. and Liao, J.C, Erythrocyte nitric oxide transport reduced by a submembrane cytoskeletal barrier, Biochimica et Biophysica Acta, 2005, 1723, 135-42.

Rohlin, L. Trent, J. D. Salmon, K. Kim, U. Gunsalus, R. P. Liao, J. C. , Heat shock response of Archaeoglobus fulgidus, J Bacteriol, 2005, 187 (17), 6046-57.

Yang, Y.L.; Suen, J.; Brynildsen,M.P.; Galbraith, S.J.; Liao, J.C., Inferring yeast cell cycle regulators and interactions using transcription factor activities, BMC Genomics, 2005, 6 (1), 90.

Zhou, B. Beckwith, D. Jarboe, L. R. Liao, J. C. , Markov Chain modeling of pyelonephritis-associated pili expression in uropathogenic Escherichia coli, Biophys J, 2005, 88 (4), 2541-53.

Zhou, B.; D. Beckwith; L. R. Jarboe, and J.C. Liao, Markov Chain Modeling of Pyelonephritis-Associated Pili Expression in Uropathogenic Escherichia coli, Biophysical J. , 2005, 88, 2541-2553.

Rohlin, L.;Trent, J.D.; Salmon, K; Kim, U.; Gunsalus, R.P.; and Liao, J.C., The heat-shock response of Archaeoglobus fulgidus, J. Bacteriol., 2005, 187, 6046-6057.

Brynildsen, M. P. Wong, W. W. Liao, J. C. , Transcriptional regulation and metabolism, Biochem Soc Trans, 2005, 33 (Pt 6), 1423-6.

Brynildsen, M.P.;Wong, W.W.; and Liao, J.C. , Transcriptional regulation and metabolism, Biochem. Soc. Trans. , 2005, 33, 1423-1426.

Sabatti, C; Rohlin, L; Lange, K; and Liao, J.C., Vocabulon: a dictionary model approach for reconstruction and localization of transcription factor binding sites, Bioinformatics. 2005 Apr 1, 2005, 21 (7), 922-31.

Sriram, G; Martinez, J.A.; McCabe, E.R.B.; Liao, J.C.; and Dipple, K.M., What Role Could Moonlighting Enzymes Play? , Am. J. Hum. Genet., 2005, 76, 911-924.

Tran, L.M.; M.P. Brynildsen; K. C. Kao; J. K. Suen and J. C. Liao, gNCA: A framework for determining transcription factor activity based on transcriptome: Identifiability and numerical implementation, Metabolic Engineering., 2005, 7 , 128-141.

Tran, L. M. Brynildsen, M. P. Kao, K. C. Suen, J. K. Liao, J. C. , gNCA: a framework for determining transcription factor activity based on transcriptome: identifiability and numerical implementation, Metab Eng, 2005, 7 (2), 128-41.

Liao, J.C., Custom Design of Metabolism, Nature Biotechnol., 2004, 22, 823-824.

Bulter, T;. Lee, S.-G.; Wong, W.W.; Fung, E.; Connor, M.R. and Liao, J.C., Design of artificial cell-cell communication using gene and metabolic networks, Proc. Natl. Acad. Sci. USA, 2004, 101, 2299-2304 [Commentary by Gerchman and Weiss, PNAS, 2004 101:2221-2222].

Han, T.H.; Fukuto,J.M., and Liao, J.C., Reductive nitrosylation and S-nitrosation of hemoglobin in inhomogeneous nitric oxide solutions, Nitric Oxide Biology and Chemistry, 2004, 10, 74-82.

Jarboe, L. R. Beckwith, D. Liao, J. C. , Stochastic modeling of the phase-variable pap operon regulation in uropathogenic Escherichia coli, Biotechnol Bioeng, 2004, 88 (2), 189-203.

Jarboe, L.R; Beckwith, D; Liao, J.C., Stochastic modeling of pap operon regulation in uropathogenic Escherichia coli, Biotechnol. Bioeng., 2004, 88, 189-203.

Kao, K. C. Yang, Y. L. Boscolo, R. Sabatti, C. Roychowdhury, V. Liao, J. C. , Transcriptome-based determination of multiple transcription regulator activities in Escherichia coli by using network component analysis, Proc Natl Acad Sci U S A, 2004, 101 (2), 641-6.

Hyduke, D. R. Rohlin, L. Kao, K. C. Liao, J. C. , A software package for cDNA microarray data normalization and assessing confidence intervals, OMICS, 2003, 7 (3), 227-34.

El-Farra, N.H.;P. D. Christofides and J. C. Liao, Analysis of Nitric Oxide Transport Barriers in Blood Vessels Using a Distributed Multi-cellular Model, Annals of Biomedical Engineering, 2003, 31, 294-309.

El-Farra, N. H. Christofides, P. D. Liao, J. C. , Analysis of nitric oxide consumption by erythrocytes in blood vessels using a distributed multicellular model, Ann Biomed Eng, 2003, 31 (3), 294-309.

Han TH, Qamirani E, Nelson AG, Hyduke DR, Chaudhuri G, Kuo L, and Liao JC, Regulation of Nitric Oxide Consumption by Hypoxic Red Blood Cells, Proc. Natl. Acad. Sci. USA, 2003, 100, 12504-12509.

Wang, C.W.;T.H. Han, and J. C. Liao, Sequence Analysis for Metabolic Evolution of Archaeoglobus fulgidus Geranylgeranyl Diphosphate Synthase in Escherichia coli for Carotenoid Biosynthesis, J. Chin. Inst. Chem. Eng ., 2003, 34, 47-56.

Bulter, T.; J.R. Bernstein; and J.C. Liao, Strategies of metabolic engineering: Moving up the systems hierarchy, Biotechnol. Bioeng., 2003, 84, 815-821.

Hatzimanikatis, V. Liao, J. C. , A memorial review of Jay Bailey's contribution in prokaryotic metabolic engineering, Biotechnol Bioeng, 2002, 79 (5), 504-8.

Liao, JC, Blood feud: Keeping hemoglobin from nixing NO, Nature Medicine, 2002, 8, 1350-1351.

Sabatti, C. Rohlin, L, Oh, M.K., and Liao, J.C., Co-expression pattern from DNA microarray experiments as a tool for operon prediction, Nucl. Acids. Res. , 2002, 30, 2886-2893.

Rohlin, L., M.-K. Oh, and J. C. Liao, DNA Microarray For Microbial Biotechnology: Gene Expression Profiles in Escherichia coli During Protein Overexpression (invited paper), J. Chin. Inst. Chem. Eng., 2002, 33, 103-112 .

Oh, M. K. Rohlin, L. Kao, K. C. Liao, J. C. , Global expression profiling of acetate-grown Escherichia coli, J Biol Chem, 2002, 277 (15), 13175-83.

Liao, JC and Sabatti, C., Microanalysis of DNA microarrays, ASM News, 2002, 68, 432-437.

Joshi, M.S., Ferguson, T.B., Han,T.H., Hyduke, D.R., Liao,J.C., Rassaf, T., Bryan, N., Feelisch, M., and Lancaster, J.R., Nitric Oxide is Consumed, Rather than Conserved, by Reaction with Oxyhemoglobin under Physiological Conditions, Proc. Natl. Acad. Sci. USA, 2002, 99, 10341-10346.

Han, T. H. Hyduke, D. R. Vaughn, M. W. Fukuto, J. M. Liao, J. C. , Nitric oxide reaction with red blood cells and hemoglobin under heterogeneous conditions, Proc Natl Acad Sci U S A, 2002, 99 (11), 7763-8.

Farmer, W. R. Liao, J. C. , Acetate-inducible protein overexpression from the glnAp2 promoter of Escherichia coli, Biotechnol Bioeng, 2001, 75 (5), 504-9.

Wang, C. W. Liao, J. C. , Alteration of product specificity of Rhodobacter sphaeroides phytoene desaturase by directed evolution, J Biol Chem, 2001, 276 (44), 41161-4.

Vaughn, M. W. Huang, K. T. Kuo, L. Liao, J. C. , Erythrocyte consumption of nitric oxide: competition experiment and model analysis, Nitric Oxide, 2001, 5 (1), 18-31.

Barkovich, R. Liao, J. C. , Metabolic engineering of isoprenoids, Metab Eng, 2001, 3 (1), 27-39.

Rohlin, L. Oh, M. K. Liao, J. C. , Microbial pathway engineering for industrial processes: evolution, combinatorial biosynthesis and rational design, Curr Opin Microbiol, 2001, 4 (3), 330-5.

Huang, K. T. Han, T. H. Hyduke, D. R. Vaughn, M. W. Van Herle, H. Hein, T. W. Zhang, C. Kuo, L. Liao, J. C. , Modulation of nitric oxide bioavailability by erythrocytes, Proc Natl Acad Sci U S A, 2001, 98 (20), 11771-6.

Farmer, W. R. Liao, J. C. , Precursor balancing for metabolic engineering of lycopene production in Escherichia coli, Biotechnol Prog, 2001, 17 (1), 57-61.

Oh, M. K. Liao, J. C. , DNA microarray detection of metabolic responses to protein overproduction in Escherichia coli, Metab Eng, 2000, 2 (3), 201-9.

Wang, C. Oh, M. K. Liao, J. C. , Directed evolution of metabolically engineered Escherichia coli for carotenoid production, Biotechnol Prog, 2000, 16 (6), 922-6.

Vaughn, M. W. Huang, K. T. Kuo, L. Liao, J. C. , Erythrocytes possess an intrinsic barrier to nitric oxide consumption, J Biol Chem, 2000, 275 (4), 2342-8.

Oh, M. K. Liao, J. C. , Gene expression profiling by DNA microarrays and metabolic fluxes in Escherichia coli, Biotechnol Prog, 2000, 16 (2), 278-86.

Farmer, W. R. Liao, J. C. , Improving lycopene production in Escherichia coli by engineering metabolic control, Nat Biotechnol, 2000, 18 (5), 533-7.