Charles M. Roth

Tel: (732) 445-4109
Fax: (732) 445-2581
Email: cmroth@rci.rutgers.edu
Webpage: Dr. Roth's Home Page

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

  Recently, a "rough draft" of the human genome was completed, with the promise of great improvements in understanding of human biology and concomitant advances in diagnosis and treatment of disease. One of the emerging technologies that utilizes genetic information is antisense technology, in which a short single-stranded oligonucleotide with a sequence complementary to a defined region on a target mRNA is introduced to block the translation of the mRNA into protein. We are working towards overcoming some of the technical barriers to antisense effectiveness. We have recently developed a molecular thermodynamic model of DNA:RNA binding that we are using to rationally design antisense sequences of high affinity and rapid hybridization kinetics.

2. Genetic Control of Cellular Stress Responses

  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 are utilizing recent advances in the ability to monitor gene expression on a large scale, at both the transcript (DNA microarrays and quantitative kinetic RT-PCR) and protein (2-dimensional gel electrophoresis) levels, in order to uncover a deeper understanding of the molecular factors governing disease states and to develop improved therapeutic strategies for combating them. We also seek to develop models based on process control theory that segregate cellular behavior into particular modules, which can be more or less detailed depending on the amount of data available. These tools are applied to the selection of candidate molecules for therapeutic intervention in chronic inflammatory diseases (sepsis, multiple organ failure) and in guiding differentiated phenotype in cells cultured on biomaterials for tissue engineering applications.

3. Delivery of Nucleic Acids to Cells

  Among the various technologies - including gene therapy, antisense technology, and DNA vaccines - that involve administering nucleic acids to cells either in vivo or ex vivo, there exists a consistent and significant problem of delivering therapeutic quantities to the desired site without overloading the cells or body with toxic carriers or degradation products. A fundamental understanding of how gene delivery vehicles interact with cells is sorely lacking. We seek to understand vehicle-cell interactions by combining quantitative assays of adsorption with systematic variation of both physical (e.g., charge) and biological (e.g., ligand density) parameters. We will develop a physicochemical model that incorporates both specific (biological) and non-specific (physical) interactions, obtain parameters and refine it based on adsorption experiments, and use it to design materials that will achieve desired delivery profiles. New materials will be tested both for adsorption as well as in applications in disease models.

Dept. of Chemical and Biochemical Engineering, 98 Brett Road
Piscataway, NJ 08854-8058
Phone: (732) 445-2228 Fax: (732) 445-2581