Charles M. Roth

Professor

Chemical and Biochemical Engineering

Phone:848-445-6686
Fax:
Email:cmroth@rci.rutgers.edu
Office:
Website: Research Webpage

Education

Harvard Medical School

Postdoc

1995-97

Bioengineering

University of Delaware

Ph.D.

1994

Chemical Engineering

University of Pennsylvania

B.S.E.

1989

Chemical Engineering

Honors

2005

Rutgers FASIP Award for Teaching, Research and Service (ranked first in Department)

2003

NSF Faculty CAREER Award

2002, 2006

Charles & Johanna Busch Biomedical Research Award

2002

Whitaker Foundation Transitional Career Award

2000

Whitaker Foundation Travel Award

1998-99

Harvard Council on Biomedical Engineering Faculty Excellence Fellow

1995-97

NIH Postdoctoral Fellowship

1989-90

Robert L. Pigford Graduate Student Fellowship, University of Delaware

1989

American Chemical Society Scholastic Achievement Award

1988

Delaware Valley AIChE Junior Award

1985-89

Benjamin Franklin Scholar, University of Pennsylvania

Professional Affiliations

Department of Biomedical Engineering
Department of Chemical and Biochemical Engineering


Graduate Program in Biochemistry
Graduate Program in Cell and Developmental Biology
IGERT Training Program in Engineered Biointerfaces
IGERT Training Program in Nanopharaceutics
Center for Structured Organic Composites
New Jersey Center for Biomaterials 

Research Interests

OVERVIEW

Our work falls under a broad umbrella of Molecular Bioengineering: developing an understanding of molecular interactions in a biological context and exploiting this knowledge for the improved design of bioengineered products.  This encompasses activities crossing interdisciplinary boundaries and including elements of biophysics, synthetic chemistry, engineering thermodynamics and kinetics, cell and molecular biology, and physiology.  Examples of ongoing and possible projects are outlined briefly below. 

1.  Molecular Bioengineering of Antisense Oligonucleotides

The sequencing of the human genome is more or less completed, with the promise of great improvements in understanding of human biology and concomitant advances in diagnosis and treatment of disease.  Several technologies have emerged to inhibit the expression of specific target genes based on their gene sequence.  We are working towards overcoming some of the technical barriers to two of the most promising -- antisense oligonucleotides (AS ONs) and short interfering RNAs (siRNAs).  In one project, we have developed a molecular thermodynamic model of DNA:RNA binding that we are using to rationally design AS ONs of high affinity and rapid hybridization kinetics, and we are now investigating the extension of this methodology to siRNA design.  In a second project, we use cell-specific ligands and biocompatible polymers to delivery oligonucleotides to cells with improved efficiency and selectivity. 

2. Liver Systems Biology

Efforts to develop “magic bullet” molecular therapeutics have been largely unsuccessful, in large part due to poor understanding of the underlying molecular basis for the disease being treated.  Most physiological processes and disease conditions involve the concerted actions of large sets of genes, which may act synergistically, antagonistically, or in sophisticated feedback loops.  We use computational and experimental approaches to analyze systems of molecules holistically, in an effort to rationally guide molecular strategies for engineering cell function.  One application of this approach is the manipulation of transcription factor expression to confer differentiated function to cultured hepatocytes for tissue engineering applications.  Another is the use of promoter binding site preferences and gene expression profiling to analyze dynamic responses of the liver to inflammatory stress.

Selected Publications

Book Chapters

    1. Roth CM, Lenhoff AM.  Electrostatic and van der Waals contributions to protein adsorption:  computation of equilibrium constants.  Langmuir, 1993; 9:962-972.
    2. Roth CM, Lenhoff AM.  Electrostatic and van der Waals contributions to protein adsorption:  comparison of theory with experiment.  Langmuir, 1995; 11:3500-3509.
    3. Roth CM, Neal BL, Lenhoff AM.  Van der Waals interactions involving proteins.  Biophys. J., 1996; 70:977-987.
    4. Roth CM, Unger KK, Lenhoff AM.  A mechanistic model for retention in ion exchange chromatography.  J. Chromatogr., 1996; 726:45-56.
    5. Roth CM, Lenhoff AM.  Improved parametric representation of water dielectric data for Lifshitz theory calculations.  J. Colloid Interface Sci., 1996; 179:637-639.
    6. Roth CM, Reiken SR, Le Doux JM, Rajur SB, Lu X-M, Morgan JR, Yarmush ML.  Targeted antisense modulation of inflammatory cytokine receptors.  Biotechnol. Bioeng., 1997; 55:72-81.
    7. Rajur SB, Roth CM, Morgan JR, Yarmush ML.  Covalent protein-oligonucleotide conjugates for efficient delivery of antisense molecules.  Bioconjugate Chem., 1997; 8:935-940.
    8. Roth CM, Sader JE, Lenhoff AM.  Electrostatic contribution to the energy and entropy of protein adsorption.  J. Colloid Interface Sci., 1998; 203:218-221.
    9. Sundaram S, Roth CM, Yarmush ML.  Pressure-induced dissociation of antigen-antibody complexes.  Biotechnol. Prog., 1998; 14:773-781.
    10. Walton SP, Stephanopoulos GN, Yarmush ML, Roth CM.  Prediction of antisense oligonucleotide binding affinity to a structured RNA target.  Biotechnol. Bioeng., 1999; 65:1-9.
    11. Andreadis ST, Roth CM, Le Doux, JM, Morgan, JR, Yarmush, ML.  Large-scale processing of recombinant retroviruses for gene therapy.  Biotechnol. Prog., 1999, 15:1-11.
    12. Roth CM, Yarmush ML.  Nucleic acid biotechnology.  Annu. Rev. Biomed. Engr., 1999, 1:265-297.
    13. Roy P, Roth CM, Margolies MN, Yarmush ML.  Effect of pressure on antigen-antibody complexes: modulation by ionic strength and temperature.  Mol. Immunol., 1999; 36:1149-1158.
    14. Roy P, Roth CM, Margolies MN, Yarmush ML.  Aromatic residues mediate the pressure-induced association of digoxigenin and antibody 26-10.  Biophys. Chem., 1999; 83:171-177.
    15. Jayaraman A, Yarmush ML, Roth CM.  Dynamics of gene expression in rat hepatocytes under stress.  Metabolic Eng., 2000; 2:239-251.
    16. Roth CM, Kohen RL, Walton SP, Yarmush ML. Coupling of inflammatory cytokine signaling pathways probed by measurements of extracellular acidification rate.  Biophys. Chem., 2001; 89:1-12.
    17. Jayaraman A, Walton SP, Yarmush ML, Roth CM.  Rational selection and quantitative evaluation of antisense oligonucleotides.  Biochim. Biophys. Acta, 2001; 1520:105-114.
    18. Walton SP, Stephanopoulos GN, Yarmush ML, Roth CM.  Thermodynamic and kinetic characterization of antisense oligodeoxynucleotide binding to a structured mRNA.  Biophys. J., 2002; 82:366-377.
    19. Jayaraman A, Yarmush ML, Roth CM.  Molecular bioengineering.  Ind. Eng. Chem. Res., 2002; 41:441-455.
    20. Roth CM.  Quantifying gene expression.  Curr. Issues Mol. Biol., 2002; 4:93-100.
    21. Lee LK and Roth CM.  Antisense technology in molecular and cellular bioengineering.  Curr. Opin. Biotechnol., 2003; 14:505-511.
    22. Roth CM, Sundaram S.  Engineering synthetic vectors for improved DNA delivery: Insights from intracellular pathways.  Annu. Rev. Biomed. Engr., 2004; 6:397-426.
    23. Jayaraman A, Yarmush ML, Roth CM.  Evaluation of an in vitro model of hepatic inflammatory response by gene expression profiling.  Tissue Eng., 2005; 11:50-63.
    24. Roth CM.  Molecular and cellular barriers limiting the effectiveness of antisense oligonucleotides.  Biophys. J., 2005, 89:2286-2295.
    25. Sundaram S, Viriyayuthakorn S, Roth CM.  Oligonucleotide structure influences the interaction between cationic polymers and oligonucleotides.  Biomacromolecules, 2005; 6:2961-2968.
    26. Gevertz JL, Dunn SM, Roth CM.  Mathematical model of real-time PCR kinetics.  Biotechnol. Bioeng., 2005; 92:346-355.
    27. Katz JM, Roth CM, Dunn MG.  Factors that influence transgene expression and cell viability on DNA-PEI seeded collagen films. Tissue Eng., 2005; 11:1398-1406.
    28. Lee LK, Williams CL, Devore D, Roth CM.  Poly(propylacrylic acid) enhances cationic lipid mediated delivery of antisense oligonucleotides.  Biomacromolecules, 2006; 7:1502-1508.
    29. Lee LK, Dunham BM, Li Z, Roth CM.  Cellular dynamics of antisense oligonucleotides and short interfering RNAs.  Ann. N.Y. Acad. Sci., 2006; 1082:47-51.
    30. Moghe PV and Roth CM.  Multidisciplinary graduate curriculum on integrative biointerfacial engineering.  Chem. Eng. Educ., 2006; 40:251-258.
    31. Sundaram S, Lee LK, Roth CM. Interplay of polyethyleneimine molecular weight and oligonucleotide backbone chemistry in the dynamics of antisense activity.  Nucleic Acids Res , 2007; 35:4396-4408.
    32. Burley MR, Roth CM. Effects of Retinoic Acid on Proliferation and Differentiation of HepG2 Cells. Open Biotechnology Journal, 2007; 1:47-51.
    33. Roth CM.  Quantitative measurements and rational materials design for intracellular delivery of oligonucleotides.  Biotechnol. Prog., 2008; 24:23-28.
    34. Ierapetritou MG, Georgopoulos PG, Roth CM, Androulakis IP. Tissue-Level Modeling of Xenobiotic Metabolism in Liver: An Emerging Tool for Enabling Clinical Translational Research. Clin. Trans. Sci., 2009; 2:228-237.
    35. Waite CL, Sparks SM, Uhrich KE, Roth CM. Acetylation of PAMAM dendrimers for cellular delivery of siRNA. BMC Biotechnol., 2009; 9:38.
    36. Yang H, Roth CM, Ierapetritou MG. A rational design approach for amino acid supplementation in hepatocyte culture. Biotechnol. Bioeng., 2009; 103:1176-1191.
    37. Peddada LY, Harris, NK, Devore DI, Roth CM. Novel graft copolymers enhance in vitro delivery of antisense oligonucleotides in the presence of serum. J. Control. Rel., 2009; 140:134-140. (free PMC version)
    38. Waite CL, Roth CM. PAMAM-RGD conjugates enhance siRNA delivery through a multicellular spheroid model of malignant glioma. Bioconjugate Chem., 2009; 20:1908-1916.
    39. Iyer VV, Yang H, Ierapetritou MG, Roth CM. Effect of glucose and insulin on HepG2-C3A cell metabolism. Biotechnol. Bioeng., 2010; 107:347-356. Selected as journal Spotlight article.
    40. Naczynski DJ, Andelman T, Pal D, Chen S, Riman RE, Roth CM, Moghe PV. Albumin nanoshell encapsulation of near-infrared-excitable rare-earth nanoparticles enhances biocompatability and enables targeted cell imaging. Small, 2010; 6:1631-1640. Selected for journal cover.
    41. Iyer VV, Ovacik MA, Androulakis IP, Roth CM, Ierapetritou MG. Transcriptional and metabolic flux profiling of triadimefon effects on cultured hepatocytes. Toxicol. Appl. Pharmacol., 2010; 248:165-177.
    42. Yang H, Ierapetritou MG, Roth CM. Effects of amino acid transport limitations on cultured hepatocytes. Biophys. Chem., 2010; 152:89-98.
    43. Yang H, Roth CM, Ierapetritou MG. Analysis of amino-acid supplementation effects on hepatocyte cultures using flux balance analysis. OMICS, 2011; in press.
    1. Roth CM, Lenhoff AM.  Quantitative modeling of protein adsorption, In:  Malmsten M, ed., Biopolymers at Interfaces.  Marcel Dekker, New York, 1998, pp. 89-118.
    2. Roth CM, Yarmush ML.  Chromatography, size exclusion, In:  Flickinger MC, Drew, SW eds., The Encyclopedia of Bioprocess Technology:  Fermentation, Biocatalysis, & Bioseparation.  John Wiley & Sons, New York, 1999, pp. 639-650.
    3. Walton SP, Roth CM, Yarmush ML.  Antisense technology, In: The Biomedical Engineering Handbook, 2nd ed.  CRC Press LLC, Boca Raton, 2000, Chapter 103, pp. 1-19.
    4. Roth CM.  Electrophoresis: Nucleic acids, In: Encyclopedia of Analytical Science, Second Edition (Paul J. Worsfold, Alan Townshend and Colin F. Poole, eds.), Elsevier, Oxford, 2005, Vol. 2, pp. 456-460.