Research Interests
The research interests of my group fall into two categories:
(1) Spatial-Temporal Modeling of Signaling Networks
(2) Functional Genomics Tool Development
Spatial-Temporal Modeling of Signaling Networks. Amplification of genes in the ErbB family (i.e. EGFR, ErbB2, etc) is associated with poor outcome in women's cancers, including breast, ovarian and endometrial cancer. While it is clear that overexpression is a factor leading to ligand-independent signaling via these receptors, the mechanism by which functional dimerization and activation occurs is unknown. It is my hypothesis that the spatial organization and the heterogeneity of the receptors in the plasma membrane and the downstream signaling components is essential for the control of signaling pathways. The focus of my work is on the development of spatially realistic simulations with the goal of understanding the importance of spatial regulation in signal transduction. The results of my future work will provide an unprecedented level of detail regarding the changing topography of membrane organization. Results of these analyses will contribute new insight into the nature and assembly of membrane microdomains controlling signal transduction and membrane trafficking in eucaryotic cells.
Functional Genomics Tool Development. The resounding success of the Human Genome Project clearly illustrates how early investments in developing cost-effective methods of data acquisition can have tremendous payoffs for the biomedical community. We maintain that the completion of the human genome marks the end-of-the-beginning, rather than the beginning-of-the-end, of the era of nucleic-acid (NA) technologies. For a wide range of biomedical and bioagricultural goals, a strong need is evolving for low-cost NA technology. The list of realized and potential applications is rich and growing. NA technology has the potential to significantly and substantially impact cancer related health care (and health care in general), both directly by providing diagnostic and prognostic markers for the clinical setting, and indirectly by accelerating the pace of basic and clinical biomedical research.
Selected Publications
Link to PubMed
1.
Chatterjee, A., Mayawala, K., Edwards, J. S. & Vlachos, D. G. Time
accelerated Monte Carlo simulations of biological networks using the
binomial {tau}-leap method. Bioinformatics (2005).
2.
Gadkar, K. G., Doyle III, F. J., Edwards, J. S. & Mahadevan, R.
Estimating optimal profiles of genetic alterations using
constraint-based models. Biotechnol Bioeng 89, 243-51 (2005).
3.
Mayawala, K., Vlachos, D. G. & Edwards, J. S. Heterogeneities in
EGF receptor density at the cell surface can lead to concave up
scatchard plot of EGF binding. FEBS Lett 579, 3043-7 (2005).
4.
Merritt, J., Butz, J. A., Ogunnaike, B. A. & Edwards, J. S.
Parallel analysis of human glucose-6-phosphate dehydrogenase
single-nucleotide mutants via functional complementation in S.
cerevisiae using polymerase colonies. Biotech Bioeng In press (2005).
5.
Butz, J., Goodwin, K. & Edwards, J. S. Detecting changes in the
relative expression of K-ras2 splice variants using polymerase
colonies. Biotechnol Prog 20, 1836-1839 (2004).
6.
Butz, J., Yan, H., Mikkilineni, V. & Edwards, J. S. Detection of
allelic variations of human gene expression by polymerase colonies. BMC
Genetics 5 (2004).
7.
Goodkind, J. R. & Edwards, J. S. Gene Expression Measurement
Technologies: Innovations and Ethical Considerations. Computers &
Chemical Engineering In Press (2004).
8.
Mayawala, K., Gelmi, C. A. & Edwards, J. S. MAPK cascade possesses
decoupled controllability of signal amplification and duration. Biophys
J 87, L01-2 (2004).
9.
Merritt, J. & Edwards, J. S. Assaying gene function by growth
competition experiment. Metab Eng 6, 212-219 (2004).
10.
Mikkilineni, V., Mitra, R. D., DiTonno, J. R., Merritt, J., Church, G.
M., Ogunnaike, B. A. & Edwards, J. S. Digital Quantitative
Measurements of Gene Expression. Biotech Bioeng 86, 117-124 (2004).
11.
Mutalik, V. K., Singh, A. P., Edwards, J. S. & Venkatesh, K. V.
Robust global sensitivity in multiple enzyme cascade system explains
how the downstream cascade structure may remain unaffected by
cross-talk. FEBS Letters 558, 79-84 (2004).
12.
Mutalik, V. K., Singh, A. P., Edwards, J. S. & Venkatesh, K. V.
Equilibrium analysis of allosteric interactions shows zero-order
effects. Cell Biochemistry and Biophysics 41, 179-192 (2004).
13.
Patel, S. & Edwards, J. S. RecA mediated initial alignment of
homologous DNA molecules displays apparent first order kinetics with
little effect of heterology. DNA Repair 3, 61-65 (2004).
14.
Patel, S., Venkatesh, K. V. & Edwards, J. S. An integrated
mechanistic model for transcription-coupled nucleotide excision repair.
DNA Repair 3, 343-348 (2004).
15.
Ruhela, A., Verma, M., Edwards, J. S., Bhat, P. J., Bhartiya, S. &
Venkatesh, K. V. Autoregulation of Regulatory Proteins is Key for
Dynamic Operation of GAL Switch in Saccharomyces cerevisiae. FEBS Lett
576, 119-126 (2004).
16.
Altenbaugh, R. E., Kauffman, K. J. & Edwards, J. S. Suitability and
utility of computational analysis tools: characterization of
erythrocyte parameter variation. Pac Symp Biocomput, 104-15 (2003).
17.
Butz, J., Wickstrom, E. & Edwards, J. S. Characterization of
Mutations and LOH of p53 and K-ras2 in Pancreatic Cancer Cell Lines by
Immobilized PCR. BMC Biotechnol 3, 11 (2003).
18.
Edwards, J. S. & Battista, J. R. Using DNA microarray data to
understand the ionizing radiation resistance of Deinococcus
radiodurans. Trends Biotechnol 21, 381-382 (2003).
19.
Edwards, J. S. & Kauffman, K. J. Biochemical Engineering in the
21st Century. Curr Opin Biotechnol 14, 451-453 (2003).
20.
Ibarra, R. U., Fu, P., Palsson, B. O., DiTonno, J. R. & Edwards, J.
S. Quantitative Analysis of E. coli Metabolic Phenotypes within the
Context of Phenotypic Phase Planes. J Mol Microbiol Biotechnol 6,
101-108 (2003).
21.
Kauffman, K. J., Prakash, P. & Edwards, J. S. Advances in Flux
Balance Analysis. Current Opinion in Biotechnology 14, 491-496 (2003).
22.
Lall, R., Gao, G., Dhurjati, P. & Edwards, J. S. MRAD:
Metabolic Reaction Analysis Database – An Entity-Relationship Approach.
J Mol Microbiol Biotechnol 6, 12-18 (2003).
23.
Merritt, J., DiTonno, J. R., Mitra, R. D., Church, G. M. & Edwards,
J. S. Functional characterization of mutant yeast PGK1 within the
context of the whole cell. Nucleic Acids Res 31, e84 (2003).
24.
Edwards, J. S., Covert, M. W. & Palsson, B. O. Metabolic Modeling
of Microbes: the Flux-Balance Approach. Environ Microbiol 4, 133-140
(2002).
25.
Edwards, J. S., Ramakrishna, R. & Palsson, B. O. Characterizing the
metabolic phenotype: A phenotype phase plane analysis. Biotechnol
Bioeng 77, 27-36 (2002).
26.
Ibarra, R. U., Edwards, J. S. & Palsson, B. O. Evolution towards
predicted optimal growth in Escherichia coli K-12. Nature 420, 186-189
(2002).
27.
Kauffman, K. J., Pajerowski, J. D., Jamshidi, N., Palsson, B. O. &
Edwards, J. S. Description and analysis of metabolic connectivity and
dynamics in the human red blood cell. Biophys J 83, 646-62 (2002).
28.
Mahadevan, R., Edwards, J. S. & Doyle, F. J., III. Dynamic Flux
Balance Analysis of Diauxic Growth in Escherichia coli. Biophys J 83,
1331-1340 (2002).
29.
Papin, J. A., Price, N. D., Edwards, J. S. & Palsson, B. O. The
genome-scale metabolic extreme pathway structure in Haemophilus
influenzae shows significant network redundancy. Journal of Theoretical
Biology 215, 67-82 (2002).
30.
Schilling, C. H., Covert, M. W., Famili, I., Church, G. M., Edwards, J.
S. & Palsson, B. O. Genome-scale metabolic model of Helicobacter
pylori 26695. J Bacteriology 184, 4582-4593 (2002).
31.
Badarinarayana, V., Estep, P. W., 3rd, Shendure, J., Edwards, J.,
Tavazoie, S., Lam, F. & Church, G. M. Selection analyses of
insertional mutants using subgenic-resolution arrays. Nat Biotechnol
19, 1060-1065 (2001).
32.
Covert, M. W., Schilling, C. H., Famili, I., Edwards, J. S., Goryanin,
I. I., Selkov, E. & Palsson, B. O. Metabolic Modeling of Microbial
Strains in silico. Trends Biochem Sci 26, 179-86 (2001).
33.
Edwards, J. S., Ibarra, R. U. & Palsson, B. O. In silico
predictions of Escherichia coli metabolic capabilities are consistent
with experimental data. Nat Biotechnol 19, 125-130 (2001).
34.
Jamshidi, N., Edwards, J. S., Fahland, T., Church, G. M. & Palsson,
B. O. Dynamic simulation of the human red blood cell metabolic network.
Bioinformatics 17, 286-7. (2001).
35.
Ramakrishna, R., Edwards, J. S., McCulloch, A. & Palsson, B. O.
Flux-balance analysis of mitochondrial energy metabolism: consequences
of systemic stoichiometric constraints. Am J Physiol Regul Integr Comp
Physiol 280, R695-R704 (2001).
36.
Tchieu, J. H., Norris, V., Edwards, J. S. & Saier, M. H., Jr. The
complete phosphotranferase system in Escherichia coli. J Mol Microbiol
Biotechnol 3, 329-46. (2001).
37.
Edwards, J. S. & Palsson, B. O. Multiple steady states in kinetic
models of red cell metabolism. J Theor Biol 207, 125-127 (2000).
38.
Edwards, J. S. & Palsson, B. O. The Escherichia coli MG1655 in
silico metabolic genotype: its definition, characteristics, and
capabilities. Proc Natl Acad Sci U S A 97, 5528-33 (2000).
39.
Edwards, J. S. & Palsson, B. O. Robustness Analysis of the
Escherichia coli metabolic network. Biotechnol Prog 16, 927-939 (2000).
40.
Edwards, J. S. & Palsson, B. O. Metabolic flux balance analysis and
the in silico analysis of Escherichia coli K-12 gene deletions. BMC
Bioinformatics 1, 1 (2000).
41.
Schilling, C. H., Edwards, J. S., Letscher, D. & Palsson, B. O.
Combining pathway analysis with flux balance analysis for the
comprehensive study of metabolic systems. Biotechnology and
Bioengineering 71, 286-306 (2000).
42.
Edwards, J. S. & Palsson, B. O. Systems Properties of the
Haemophilus influenzae Rd Metabolic Genotype. Journal of Biological
Chemistry 274, 17410-17416 (1999).
43.
Edwards, J. S., Ramakrishna, R., Schilling, C. H. & Palsson, B. O.
in Metabolic Engineering (eds. Lee, S. Y. & Papoutsakis, E. T.)
13-57 (Marcel Deker, New York, 1999).
44.
Schilling, C. H., Edwards, J. S. & Palsson, B. O. Towards metabolic
phenomics: Analysis of genomic data using flux balances. Biotechnology
Progress 15, 288-95 (1999).
45.
Edwards, J. S. & Palsson, B. O. How will bioinformatics influence
metabolic engineering? Biotechnology and Bioengineering 58, 162-169
(1998).
