(5t) Molecular Mechanisms for the Aggregation of Proteins and Therapeutic Antibodies

My overall research goal is to understand the mechanisms behind protein and therapeutic antibody aggregation, and design proteins with enhanced stability. Antibody aggregation leads to immunogenicity and loss of activity in the pharmaceutical formulations used in the treatment of numerous cancers, chronic inflammatory diseases, and infectious diseases. Furthermore, protein aggregation in vivo is associated with a number of neurodegenerative disorders such as Alzheimer's and Creutzfeldt-Jakob diseases, and type II diabetes. We study these aggregation mechanisms using multi-scale modeling and simulation techniques in close collaboration with experiments.

I. Mechanisms for the Aggregation of Therapeutic Antibodies

In my current post-doctoral position with Prof. Bernhardt L. Trout at the Massachusetts Institute of Technology, we study the mechanism behind the aggregation of therapeutic antibodies and design antibodies with enhanced stability. Antibodies constitute the most rapidly growing class of human therapeutics. These antibodies are, however, thermodynamically unstable under conditions required for storage and administration and degrade due to aggregation. We use molecular simulation tools in collaboration with experimental techniques to identify the regions of the antibody most prone to aggregation. Subsequently, we perform mutations in these specific aggregation prone regions to engineer antibodies with enhanced stability.

II. Development of Multi-scale Modeling Techniques for Soft Condensed Matter Systems

During my PhD work with Prof. Keith E Gubbins at North Carolina State University, we developed a multi-scale methodology connecting the atomistic and meso-scale models useful in understanding the long length and time scale phenomena involved in surfactant self-assembly, polymers, colloids and protein solutions. In addition, we have developed a novel technique to determine the rigorous effective pair potentials for a simple binary A/B mixture by integrating out the degrees of freedom of solvent B using Widom's particle insertion method. We have also explored the effect of cosolvents and cosurfactants such as alcohols on surfactant self-assembly and solubilization capacity in supercritical carbon dioxide with applications in separation processes in the food industry such as extraction of water-soluble vitamins and proteins, dry cleaning and polymerization.