University of Delaware - College of Engineering
CHEMICAL & BIOMOLECULAR ENGINEERING

People

Faculty

Christopher J Roberts

Christopher  Roberts
  • Associate Professor

223 CLB
University of Delaware
Newark, Delaware 19716
cjr@udel.edu
302-831-0838
302-831-1048 (fax)


Education
  • Doctorate - 1999 Princeton University, Princeton, NJ
  • Masters - 1996 Princeton University, Princeton, NJ
  • Bachelors - 1994 University of Delaware

"Our research is generally focused on quantitative prediction, design, and control of protein degradation in solution, and of degradation of pharmaceutical and bio-pharmaceutical molecules in amorphous solids (glasses); the ultimate goal being quantitative control of the kinetic stability of labile aqueous and biological media, and the development of molecular-based engineering models to aid in design of preservation media for bio- and pharmaceutical based materials. Our research incorporates a variety of tools, including experiment, molecular simulation, and kinetic and statistical mechanical modeling.

PROTEIN AGGREGATION; PREDICTION OF PROTEIN SHELF LIFE; PROTEIN PRESERVATION

Proteins degrade in a variety of ways, including aggregation, oxidation, deamidation, and hydrolysis. The limited long-term storage stability of proteins is in fact one of the most difficult hurdles to commercial development of many protein therapeutics. Additionally, protein degradation is implicated in number of devastating diseases, such as Alzheimer's and Parkinson's, but prediction and control of the underlying processes remains elusive. Our research in this area is centered on biophysical chemistry of protein degradation, as well as the associated mathematical modeling and shelf life prediction for proteins. There is particular emphasis on understanding protein aggregation and other degradation routes from the perspective of reversible and irreversible clustering of native and non-native proteins, solvent-mediated and solute-mediated forces, interplay between chemical and physical degradation routes, and the influence of conformational state on reactivity. Our work utilizes both experimental techniques (e.g., analytical chromatography, micro-calorimetry, CD and FL spectroscopy, light scattering, and microscopy) and computational and theoretical tools to elucidate the role of protein interactions and conformation on protein aggregation, both thermodynamically and kinetically. This knowledge is in turn used, for example, to develop general models of protein aggregation kinetics that may be used to design and/or predict in vitro and in vivo behavior.

PHARMACEUTICAL & BIOLOGICAL AMORPHOUS SOLIDS (GLASSES); BIOPRESERVATION

Labile aqueous (biological) systems are inherently metastable, and will typically degrade upon long term storage (~ months to yrs.) unless deliberately preserved. Low temperatures, stabilizing additives, and/or encapsulation in "inert" solids are ubiquitous preservation techniques in both commercial and laboratory practice. Historically, these approaches have been inspired by preservation strategies found in Nature, and as such remain highly empirical. This is particularly the case for pharmaceutical and biological systems of commercial interest. The situation is further complicated by the need in many cases to rely on (at least partially) amorphous solid or glassy systems to act as preservation media. Such glassy systems are intrinsically metastable and their stability is sensitive to both their processing history (i.e., how they were prepared) and their final storage conditions. As a result, traditional models for crystalline solids or (equilibrium) liquids are inadequate, and special consideration of the thermodynamics and molecular dynamics is required in order to predict and control the properties of such materials. Work in our group uses experiment coupled with theoretical and computational statistical mechanics to develop more accurate molecular and microscopic models for the thermodynamics, dynamics, and degradation kinetics in systems such as glassy bio- and small-molelecule pharmaceuticals, food products, and biological systems under lowmoisture / low-temperature conditions. A common theme is the development of quantitative predictive models to allow rational design of bio-preservation media, as well to provide insight into novel experimental methods to preserve such labile systems."

XSelected Publications

For a complete listing of publications, please view the Full CV.
  1. Andrews, J.M.; Roberts, C.J., "A Lumry-Eyring nucleated-polymerization model of protein aggregation kinetics", J. of Phys. Chem. 111, 7897, (2007)
  2. Roberts, C.J., "Nonnative protein aggregation kinetics", Biotech. Bioeng. 98, 927, (2007)
  3. LiY, Weiss, WF IV, Roberts, CJ, "Characterization of High Molecular-Weight Nonnative Aggregates and Aggregation Kinetics by Size Exclusion Chromatography with Inline Multi-Angle Laser Light Scattering", J. Pharm. Sci. 98, 3997, (2009)
  4. Top A, Roberts CJ*, Kiick KL*, "Conformational and aggregation properties of a PEGylated alanine-rich polypeptide", Biomacromolecules 12, 2184, (2011)
  5. Blanco MA, Sahin E, Li Y, Roberts CJ*, "Reexamining Protein-Protein and Protein-Solvent Interactions from Kirkwood-Buff Analysis of Light Scattering in Multi-Component Solutions", J Chem Phys 134, 1, (2011)
  6. Sahin E, Jordan JL, Zhang A, Naranjo A, Costanzo JA, Weiss WF IV, Spatara ML, Robinson AS, Fernandez EJ*, Roberts CJ, "Computational design and biophysical characterization of point mutations for gamma-Dcrystallin illustrate a balance conformational stability and intrinsic aggregation propensity", Biochemistry 50, 628, (2011)
  7. Brummitt RK, Nesta DP, Chang L, Chase SF, Laue TM, Roberts CJ, "Non-native aggregation of an lgG1 antibody in acidic conditions: 1. Unfolding, colloidal interactions, and formation of amyloid-like high molecular weight aggregates", J Pharm Sci 100, 2087, (2011)
  8. Kim N, Remmele RL, Liu D, Razinkhov V, Fernandez EJ, Roberts CJ, "Aggregationof Anti-Streptavidin Immunoglobulin Gamma-1 Mediated by Fab Unfolding and Competing Growth Pathways", Biophys Chem 172, 26, (2013)
  9. Roberts CJ, Nesta DP, Kim N, "Effects of temperature and osmolytes on parallel degradation routes for an IgG1 antibody", J Pharm Sci 102, 3556, (2013)
  10. Weiss WF IV, Zhang A, Jordan JL, Ivanova MA, Sahin E, Fernandez EJ, Roberts CJ, "Reduction of the C191-C220 disulfide of a-chymotrypsinogen A accelerates amyloid formation via reduced nucleation barriers", Biophys Chem 185, 79, (2014)

XPatents

XSelected Awards

For a complete listing of awards, please view the Full CV.
  1. Nominated for University Excellence-in-Teaching Award (University of Delaware: 2009)
  2. College of Engineering Excellence in Teaching Award (University of Delaware: 2008)
  3. Selected as one of the "Top Reviewers for the Journal of Pharmaceutical Sciences": 2007
  4. University of Kansas, American Association of Pharmaceutical Sciences (AAPS), Student Chapter, Pharmaceutics Lecturer: 2006
  5. AAPS New Investigator Award in Pharmaceutics and Pharmaceutical Technologies (AAPS: 2005)
  6. New Investigator Grant (Pfizer Global Research & Development: 2005)
  7. Merck Faculty Fellow (University of Delaware: 2004 - 2007)
  8. Ebert Prize (American Pharmacists Association: 2004)
  9. Barry M. Goldwater Scholarship: 1992


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