Delivery System

Current delivery systems bring one type of biomolecule, e.g., one protein or one gene, at a time to the targeted site. We are developing platforms to integrate polymers with biomolecules, such as aptamers, to deliver multiple biomolecules to a targeted pathway or site.

Metabolic Profiling

In this project, metabolic engineering will be applied to further our mechanistic understanding of diseases, such as Type II diabetes, Parkinson's and Alzheimer diseases. The objective of this project is to quantify the pathway alterations in response to environmental mediators. Knowledge of in-vivo flux distributions in cells at different physiological states is of increasing importance by providing "cellular" targets for evaluation as predictors of the disease.

Systems Biology

This is the study of biology as an integrated system of genetic, protein, metabolite, cellular, and pathway events that are continually changing and inter-related. Gene expression data provide information on pathways relevant to the metabolic models. Although genes yield informative clues to diseases, they do not contain functional information. Disease mechanisms can stem from genetic and environmental causes. The importance of studying biology as a system rather than one gene or protein at a time has become increasingly relevant with the advent of high throughput genomic and proteomic technologies. A systems approach can help explain why some genes respond to a particular environmental stimulus, while others do not.

Tissue Engineering

Tissue engineering aims to improve or replace biological functions. Our goal is to design cellular co-culture systems and manipulate cellular microenvironment to reflect in vitro the metabolism in vivo. Nonparenchymal cells can aid parenchymal cells to maintain functions, but they can also mediate deleterious effects. An advantage of this technique, upon which we will capitalize, is the ability to control the cell seeding density and the spatial orientation and placement of different cell types.

Reviewed Journal Publications

Dalkic, E.; Wright, N. T.; and Chan, C. "Drug-cancer type association based networks", submitted, (2009).

Yang, X.; Opperman, M. J.; Chan, C. "PKR differentially regulates IRS1 and IRS2 in HepG2 cells", in review, (2009).

Zhang, L.; Seitz, L. C.; Abramczyk, A. M.; Chan, C. "Synergistic effect of cAMP and palmitate in promoting altered mitochondria function and cell death in HepG2 cells", in review, (2009).

Mehrotra, S.; Lynam, D.; Maloney, R.; Pawelec, K. M.; Tuszynski, M.; Lee, I.; Chan, C.; Sakamoto, J.; "Time controlled protein release from layer-by-layer assembled multilayers functionalized agarose hydrogels", Advanced Functional Materials, in press (2009).

Yang, X.; Chan, C. "Repression of PKR Mediates Palmitate-Induced Apoptosis in HepG2 Cells through Bcl-2", Cell Research, 19(4), 469-486, (2009) .

Dalkic, E.; Nash, D. E. W.; Fassia, M. K.; and Chan, C. "Integrative Analysis of Cancer Pathway Progression", Proteomics - Clinical Applications, 3, 473-85, (2009).

Leekumjorna, S.; Cho, H. J.; Wu, Y.; Wright, N. T.; Sum, A. K.; Chan, C. "Fatty Acid Induced Toxicity: The Role of Saturation in Degrading and Benefiting Cell Survival", Biochimica et Biophysica Acta - Biomembranes, 1788, 1508-1516, (2009).

Mehrotra, S.; Lee, I.; Chan, C. "Multilayer Mediated Forward Patterned siRNA Transfection using Linear-PEI at Extended N/P Ratios," Acta Biomaterialia, 5, 1474-1488, (2009).

Yang, X.; Zhou, Y.; Jin, R.; Chan, C., "Reconstruct modular phenotype-specific gene networks by knowledge-driven matrix factorization", Bioinformatics, 25(17), 2236-2243, (2009).

Wu, M., Yang, X., and Chan, C., "A dynamic analysis of insulin signaling and its feedback mechanisms: A discrete modeling approach", PLoS ONE, in press (2009).

Srivastava, S. and Chan, C., "Application of Metabolic Flux Analysis to Identify the Mechanisms of Free Fatty Acid Toxicity to Human Hepatoma Cell Line, HepG2", Biotechnology and Bioengineering 99: 399-410, (2008).

Kidambi, S.; Lee, I.; Chan, C. "Patterned Co-culture of Neurons and Astrocytes on Polyelectrolyte Multilayer Films for Studying Astrocyte Mediated Oxidative Stress in Neurons," Advanced Functional Materials 18(2), 294 - 301, (2008).

Kidambi, S.; Chan, C.; Lee, I. "Tunable Resistive m-dPEG Acid Patterns on Polyelectrolyte Multilayers at Physiological Condition for Directed Deposition of Multiple Biomacromolecules," Langmuir 24(1), 224 -230, (2008).

Li, Z.; Srivastava, S.; Findlan, R.; Chan, C. "Using dynamic gene module map analysis to identify targets that modulate free fatty acid and tumor necrosis factor (TNF)-α induced cytotoxicity," Biotechnology Progress, 24(1), 29-37, (2008).

Jin, R.; Si, L.; Chan, C. "A Bayesian Framework for Knowledge Driven Regression Model in Micro-array Data Analysis," International Journal of Data Mining and Bioinformatics (IJDMB), 2(3): 250-267 (2008).

Patil, S.; Balu, D.; Melrose, J.; Chan, C. "Brain region specificity of palmitic acid-induced Alzheimer-like changes in primary neurons", BMC Research Notes, June 4; 1(1):20, (2008).

Leekumjorn, S.; Wu, Y.; Sum, A.K.; and Chan, C. "Experimental and Computational Studies Investigating Trehalose Protection of HepG2 Cells from Palmitate Induced Cytotoxicity", Biophysical Journal, 94, 1-15, (2008).

Srivastava, S., Zhang, L., Jin, R. and Chan, C. "A novel unsupervised classification and feature selection method which incorporates ontology information" PLoS One, 3(12):e3869, (2008).

Li, Z.; Srivastava, S.; Yang, X.; Mittal, S.; Norton, P.; Resau, J.; Haab, B.; Chan, C., "A Hierarchical Approach to Identify Pathways that Confer Cytotoxicity in HepG2 Cells from Metabolic and Gene Expression Profiles", BMC Systems Biology, May 11;1(1):21, (2007).

Kidambi, S.; Sheng, L.; Lee, I; and Chan, C., "Selective Adhesion of Primary Cells in Protein-Free Polyelectrolyte Multilayer Films- Templates for Patterned Cell Co-cultures", Macromolecular Bioscience, 7(3), 344 - 353, (2007).

Srivastava, S.; Chan, C. "Hydrogen peroxide and hydroxyl radical mediate palmitate-induced cytotoxicity to hepatoma cells: relation to MPT," Free Radical Research, 41(1),38-49, (2007).

Li, Z.; Srivastava, S.; Mittal, S.; Yang, X.; Sheng, L.; and Chan, C. "A Three Stage Integrative Pathway Search (TIPS©) framework to identify toxicity relevant genes and pathways", BMC Bioinformatics June 14;8(101):1-17, (2007).

Kidambi, S.; Udpa, N.; Schroeder, S.A.; Findlan, R.; Lee, I.; Chan, C. "Cell Adhesion on Polyelectrolyte Multilayer Coated Polydimethylsiloxane Surfaces with Varying Topographies," Tissue Engineering 13, 2105-2117, (2007).

Patil, S.; Melrose, J.; and Chan, C. "Involvement of astroglial ceramide in palmitic acid-induced Alzheimer-like changes in primary neurons", European Journal of Neuroscience 26(8):2131-2141, (2007).

Srivastava, S.; Li, Z.; Yang, X.; Yedwabnick, M., Shaw, S.; and Chan, C. "Identification of genes that regulate multiple cellular processes/ responses in the context of lipotoxicity in hepatoma cells" BMC Genomics 8:364, (2007).

Patil, S.; Sheng, L.; Masserang, A.; Chan, C. "Palmitic acid-induced BACE1 upregulation and accumulation of C-terminal fragment of APP in primary cortical neurons," Neuroscience Letters, 406, 55-59, (2006).

Li, Z., Shaw, S. M., Yedwabnick, M. J., and Chan, C., "Using a state-space model with hidden variables to infer transcription factor activities," Bioinformatics, 22(6), 747-754, (2006).

Patil, S.; Chan, C. "Palmitic and stearic fatty acids induce Alzheimer-like hyperphosphorylation of tau in primary rat cortical neurons," Neuroscience Letters, 384(3), 288-293 (2005).

Kidambi, S.; Lee, I.; Chan, C. "Controlling Primary Hepatocyte Adhesion and Spreading on Protein Free Polyelectrolyte Multilayer Films," Journal of the American Chemical Society 126 (50), 16286 -16287 (2004).

Kidambi, S.; Chan, C.; Lee, I. "Selective Depositions on Polyelectrolyte Multilayers: Self-Assembled Monolayers of m-dPEG Acid as Molecular Templates," Journal of the American Chemical Society 126, 4697-4703 (2004).

Hwang, D. H.; Stephanopoulos, G.; Chan, C. "Inverse modeling using multi-block PLS to determine the environmental conditions that provide optimal cellular function," Bioinformatics 20, 487-499, (2004).

Li, Z.; Chan, C. "Inferring pathways and networks with a Bayesian framework," FASEB J 18(6), 746-748, (2004).

Li, Z.; Chan, C. "Integrating gene expression and metabolic profiles," Journal Biological Chemistry 279, 27124-27137, (2004).

Li, Z.; Yarmush, M. L.; Chan, C. "Insulin concentration during pre-conditioning mediates the regulation of urea synthesis in primary rat hepatocytes during exposure to amino acid supplemented plasma," Tissue Engineering 10(11), 1737-1746, (2004).

Chan, C.; Berthiaume, F.; Dwarakanath, B.; Tilles, A. W.; Toner, M.; Yarmush, M. L. "Hepatic tissue engineering for adjunct and temporary liver support: Critical technologies," Liver Transplantation 10(11), 1331-1342, (2004).

Li, Z.; Chan, C. "Extracting novel information from gene expression data," Trends in Biotechnology 22, 381-383, (2004).

Chan, C.; Berthiaume, F.; Lee, K.; Yarmush, M.L. "Metabolic Flux Analysis of Cultured Hepatocytes Exposed to Plasma", Biotechnology and Bioengineering 81, 33-49, (2003).

Chan, C.; Hwang, D. H.; Stephanopoulos, G. N.; Yarmush, M. L.; Stephanopoulos, G. "Application of Multivariate Analysis to Optimize Function of Cultured Hepatocytes", Biotechnology Progress 19, 580-598, (2003).

Chan, C.; Berthiaume, F.; Lee, K.; Yarmush, M. L.; "Metabolic flux analysis of hepatocyte function in hormone- and amino acid-supplemented plasma", Metabolic Engineering 5, 1-15, (2003).

Hwang, D.H.; Stephanopoulos, G.; Chan, C. "Inverse modeling using multi-block PLS to determine the environmental conditions that provide optimal cellular function", Bioinformatics, (2003).

Chan, C.; Berthiaume, F.; Washuzu, J.; Toner, M.; Yarmush, M. L. "Metabolic Pre-Conditioning of Cultured Cells in Physiological Levels of Insulin: Generating Resistance to the Lipid Accumulating Effects of Plasma in Hepatocytes", Biotechnology and Bioengineering 78, 753-760, (2002).

Washizu, J.; Berthiaume, F.; Chan, C.; Tompkins, R. G.; Toner, M.; Yarmush, M. L. "Optimization of Rat Hepatocyte Culture in Citrated Human Plasma", J. of Surgical Res. 93, 237-246, (2000).

Washizu, J.; Chan, C.; Berthiaume, F.; Tompkins, R. G.; Toner, M.; Yarmush, M. L. "Amino Acid Supplementation Improves Cell-Specific Functions of the Rat Hepatocytes Exposed to Human Plasma", Tissue Eng. 6, 497-504.(2000).

Heng, L.; Chan, C.; Churchill, S. W. "Essentially Exact Characteristics of Turbulent Convection in a Round Tube", Chem. Eng. J. 71, 163-173, (1998).

Brown, M.; Chan, C.; Targett, M.; Holtzmuller, M.; Churchill, S. W. "Combustion of Ethane with Small Concentrations of Methyl Chloride in a Refractory Tube Burner", Comb. Sci. and Tech., 115: 207-227, (1996).

Churchill, S. W.; Chan, C. "Turbulent Flow in Channels in Terms of Local Turbulent Shear Stress and Normal Stresses", AIChE J. 41:2513-2521, (1995).

Churchill, S. W.; Chan, C. "Theoretically Based Correlating Equations for the Local Characteristics of Fully Turbulent Flow in Round Tubes and between Parallel Plates", I&EC Res. 34, 1332-1341, (1995).

Books, Chapters, Monographs

Srivastava, S.; Li, Z.; Chan, C. "Identification of gene-networks associated with cell-death in lipotoxicity", in Methods in Molecular Biology: Caspase Regulation, ed. Jeffrey Varner, Humana Press Inc., Totowa, NJ, in press, (2009).

Yang, X.; Wang, X.; Wu, M., Dalkic, E.; and Chan, C. "Construction of the gene network by synergy analysis of the genes related to palmitate-induced cytotoxicity", Methods in Bioengineering in Systems Analysis of Biological Networks, eds. Arul Jayaraman & Juergen Hahn, Artech House Publishers, Chapter 5, p. 75 - 93, (2009).

Chan, C., Li, Z., and Srivastava, S., "Integration of Micro-Array and Metabolic Data", Mathematical Modeling in Experimental Nutrition, Chapter 5, p. 82-96, (2007).

Patil, S.; Li, Z.; Chan, C. "Approaches to Optimizing Cellular Function of Engineered Tissue: Cellular to Tissue Informatics," In Advances in Biochemical Engineering/Biotechnology, volume 102, Lee, K.; Kaplan, D., Eds., Springer: UK, volume 102, p. 139-159, (2006).

Berthiaume, F.; Tilles, A. W.; Toner, M.; Yarmush, M. L.; Chan, C. "Hepatic Tissue Engineering for Adjunct and Temporary Liver Support," In Tissue Engineering and Artificial Organs, Joseph D. Bronzino, Ed., Taylor and Francis, Chapter 59, p. 1-19, (2006).

Berthiaume, F.; Chan, C.; Yarmush, M. L. "Liver, Bio-artificial" In Encyclopedia of Biomaterials and Biomedical Engineering, G. Wnek; G. Bowlin, Eds.; Marcel Dekker Inc.: New York, Vol. 1, 899-909, (2004).

Reviews

Li, Z.; and Chan, C. "Systems biology for identifying liver toxicity pathways", BMC Proceedings, 3(Suppl 2):S2, (10 March 2009).

Chan, C.; Wang, X. Review of Systems Biological Approaches in Infectious Diseases, edited by Helen I. Boshoff and Clifton E. Barry, III, (2009) ChemMedChem, 4, 1-3.

Wang, X.; Wu, M.; Dalkic, E.; Chan, C. "Gene-module level analysis: Identification to Networks and Dynamics", Current Opinion in Biotechnology, 19, 482-491, (2008).

Wang, X.; Wu, M.; Li, Z.; Chan, C. "Short time-series microarray analysis: methods and challenges", BMC Systems Biology, 2:58, (2008).

Walton, S. P.; Li, Z.; Chan, C. "Biological network analyses: computational genomics and systems approaches," Molecular Simulation 32(3-4), 203-209, (2006).

Li, Z.; Chan, C. "Extracting novel information from gene expression data," Trends in Biotechnology 22, 381-383, (2004).

Chan, C.; Berthiaume, F.; Dwarakanath, B.; Tilles, A. W.; Toner, M.; Yarmush, M. L. "Hepatic tissue engineering for adjunct and temporary liver support: Critical technologies", Liver Transplantation 10(11), 1331-1342, (2004).

Conference Proceedings

Wu, M., Yang, X., and Chan, C., "A dynamic analysis of insulin signaling and its feedback mechanisms: A discrete modeling approach", RECOMB Regulatory Genomics and Systems Biology, (2009).

Zhou, Y.; Li, Z.; Yang, X.; Zhang, L.; Srivastava, S.; Jin, R.; and Chan, C. "Using Knowledge Driven Matrix Factorization to Reconstruct Modular Gene Regulatory Network", the Twenty-Third AAAI Conference on Artificial Intelligence (AAAI-08), (2008).

Kidambi, S.; Lee, I.; Chan, C. "Aptamer incorporated polyelectrolyte multilayer films targeting influenza virus's hemagglutinin binding region," Polymeric Materials: Science and Engineering 97, 246-247, (2007).

Jin, R.; Si, L.; Srivastava, S.; Li, Z.; Chan, C. "A Knowledge Driven Regression Model for Gene Expression and Microarray Analysis," EMBC Conference Proceedings, (2006).

Kidambi, S.; Lee, I.; Chan, C. "Salt Tunable m-dPEG Acid Patterns on Polyelectrolyte Multilayers - Templates for Directed Deposition of Macromolecules," Polymer Preprints 47(1), 41-42, (2006).

Li, Z.; Srivastava, S.; and Chan, C. "Integrating Gene Expression and Metabolic Profiles to Infer Pathways and Networks that Confer Palmitate Induced Cytotoxicity in HEPG2 Cells," ASME Summer Bioengineering Conference Proceedings, (2005).

Kidambi, S.; Lee, I. Chan, C., "Polyelectrolyte Multilayer as Bioactive Surface for Cell Adhesion," Polymer Preprints 46(2), 1271-1272, (2005)

Kidambi, S.; Lee, I.; Chan, C. Selective Primary Hepatocyte Adhesion on Polyelectrolyte Multilayer: Template for Patterned Cell Co-Culture. In AIChE Nanotechnology Proceedings (2004).

Kidambi, S.; Lee, I.; Chan, C. "Engineering Polyelectrolyte Multilayer (PEM) Surfaces to Create Cell Resistant and Adhesive Surfaces" Polymer Preprints 45(1), 88-89, (2004).

Kidambi, S.; Lee, I.; Chan, C. "Engineering Polyelectrolyte Multilayer (PEM) Surfaces to Create Cell Resistant and Adhesive Surfaces" Polymer Preprints 45(1), 88-89, (2004).

Kidambi, S.; Lee, I.; Chan, C. Selective Primary Hepatocyte Adhesion on Polyelectrolyte Multilayer: Template for Patterned Cell Co-Culture. In AIChE Nanotechnology Proceedings (2004).

Chan, C.; Li, Z. "Inferring the Hepatic Network from Experimental Measurements using Bayesian Network Analysis", ASME Summer Bioengineering Conference Proceedings, (2003).

Chan C., Washizu, J., Berthiaume F., Toner, M., and Yarmush, M. L., "Application of Metabolic Engineering to Cellular Processes of the Liver: As Use in the Development of the Bioartificial Liver", ASME Summer Bioengineering Conference Proceedings 50, 357-8, (2001).

Chan, C.; Tannenbaum, P. "1997 Inter-Society Color Council Annual Meeting and the Color & Appearance Division of the Society of Plastics Engineers", Color Research and Application, 23, (1998).

Other Works

Huebner, M.; Kroos, L.; Chan, C.; Sun, F.; and Cheng, T. "Biological Networks: Design and Dynamics at Different Levels," Department of Statistics and Probability, Technical Report MSU RM639, (2005).

Jin, R., Si, L., Chan, C., "Improve the Linear Regression Model in Bioinformatics Using Text Mining", Technical Report (MSU-CSE-06-9) of Computer Science and Engineering Dept. of Michigan State University (2006).