JANICE ANTOINE LUMPKIN

Assistant Professor

S.B. 1980, Chemical Engineering, Massachusetts Institute of Technology
M.S. 1984, Chemical Engineering, University of Pennsylvania
Ph.D. 1988, Chemical Engineering, University of Pennsylvania

Description of Research:

Protein Instability and Kinetic Modeling of Biological Systems . The successful use of polypeptides and proteins in industrial, analytical, food-related and therapeutic applications has been impeded by numerous stability (molecular integrity) problems. Long-term fermentation and cell culture operations are often limited by inactivation of key biosynthetic enzymes. Commercialization of therapeutic proteins has been severely limited by loss of activity and formation of impurities during processing and storage, and by increasingly stringent regulatory (governmental approval) requirements concerning product efficacy, purity and safety. Metal ion-catalyzed oxidation (MCO) of proteins is a largely unexplored class of reactions which recently have been recognized to irreversibly modify most amino acids and to inactivate or degrade several important metabolic, industrial and therapeutic proteins. MCO reactions can occur intra- or extracellularly by enzymatic or nonenzymatic pathways, and require O2, transition metals and reductants commonly found in bioreactors. These reactions typically proceed via active oxygen intermediates such as hydrogen peroxide, hydroxyl radicals and superoxide anion. In order to assess the magnitude of this stability problem and make effective process design, process control and/or protein engineering decisions, quantitative kinetic models of MCO reactions must be developed and highly reactive polypeptide sequences must be identified. Current research activities are focused in experimental measurement and mathematical modeling of rates of active oxygen formation in nonenzymatic MCO model systems and in mammalian cell culture. Electron spin resonance (ESR) techniques are being developed to study radical intermediates in model solutions; detection of nontoxic radical trapping agents is being developed for in vivo measurements. Rates of lactate dehydrogenase inactivation and selected tripeptide oxidation are under study in these systems. Simualtion models of biomolecule damage In vivo and in vitro by oxygen radicals are under development.

Publications:

• Diffusional Limitations on the Kinetics of Dehydration Reactions of Hydrated Barium Chloride
  
• Thermal and Water Vapor Effects on the Rate of the Dehydration Reactions of Hydrated Barium Chloride
  
• Hyperoxia Induces DNA Damage in Mammalian Cells
  
• Mathematical Modeling of Drug Release from Hydrogel Matrices via a Diffusion Coupled with Desorption Mechanism
  
• Smith, J.M., G. F. Payne, J. A. Lumpkin, J. S. Karns, "Enzyme-Based Strategy for Toxic Waste Treatment and Minimization," Biotech. and Bioeng., 39, 741 (1991).
• tert-Butyl hydroperoxide-mediated DNA base damage in cultured mammalian cells
  
• Conditions Promoting Metal Catalyzed Oxidations During Immobilized Cu-IDA Metal Affinity Chromatography
  
• Effect of Electrostatic Interactions on Polylysine Release Rates from Collagen Matrices and Comparison with Model Predictions
  

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Research Group

The currently active members of the group are:

Rajesh Krishnamurthy

Min Zhong

Nitin L. Mahadev

Kristen D. Bush

Janice A. Lumpkin