(4ag) Systems Biomedicine and Pharmaceutics

I am interested in research at the intersection of chemical engineering, computational science and engineering, applied mathematics, and biology. Many applications with great societal impact lie within the intersection of these disciplines, such as advanced pharmaceutical and medical technologies. The current pharmaceutical drug discovery and approval pipeline averages 13 years, has an attrition rate of 95%, costs more than $1 billion per approved drug, and has major impacts on clinical patient care. Predictive mathematical modeling has the potential to make significant improvements on this pipeline in several domains that often involve reacting systems with mass and energy transport on multiple length and time scales making them particularly challenging to understand mechanistically from experiments alone. Specifically, I am interested in modeling downstream processes related to how candidate drug compounds are put into formulations for dosing (manufacturing), how the drugs are released from the formulations inside patients (drug delivery), how the drugs are distributed throughout the human body and tissues (pharmacokinetics), and how the drugs dynamically affect physiological functions (pharmacodynamics).

Computational models for evaluating drug delivery from pharmaceutical formulations can narrow the range of experiments needed to identify successful formulation designs by predicting performance and thus can reduce the development time and drive down costs. In my PhD thesis research with Prof. Richard D. Braatz at the University of Illinois at Urbana-Champaign, I developed and solved novel, computationally-tractable, mechanistic mathematical models for autocatalytic reaction (hydrolysis) and diffusion (erosion) to predict the drug release dynamics from biodegradable polymer microspheres for use in human patients. These biodegradable polymer microspheres are used for controlled-release drug delivery—administering medicine over extended periods with a single dosage. The project was collaborative with Prof. Daniel W. Pack’s experimental drug delivery group. Also during my PhD research, I formulated a dynamic pharmacokinetic model used for controlling and optimizing the spatial distribution of growth factors delivered to stem cells for growing engineered tissues. 

Models coupled with sophisticated process control strategies allow for careful monitoring of manufacturing to reduce waste of materials and energy and to adhere to strict quality standards. My postdoctoral work at the Massachusetts Institute of Technology has focused on modeling of the physical and chemical processes involved in manufacturing pharmaceutical small molecules and biotherapeutics in order to make the production of pharmaceuticals more efficient and economical, particularly through innovative processing techniques shifting to continuous manufacturing or manufacturing on demand. In my project in the Novartis-MIT Center for Continuous Manufacturing, I developed a control-relevant, first-principles dynamic mathematical model for a continuous thin-film pharmaceutical manufacturing process. The polymer thin-film is drug-loaded and is to be used as a drug dosage formulation. The project is a collaborative effort with control engineers to design process control systems for quality-by-design industrial pharmaceutical manufacturing.  I am currently working on another project with the MIT Biomanufacturing Research Program to develop a dynamic model and control system for the small-scale on-demand production of biotherapeutics.

In my research program, I aim to develop mechanistic models of dynamic physiological processes, including metabolism and transport in biological tissues, that consider the effects of pharmaceutical treatments across multiple time and length scales to translate cellular- and tissue-level insights to clinical application. These models offer ways to predict the pharmacokinetic and pharmacodynamic interactions between drugs and their distribution and impact on the human body, the impact of controlled-release drug delivery dosages on tissue-level responses, and role of therapeutics and metabolites in the pathology of diseased populations. I am currently building collaborations with experimentalists at other universities for validating the modeling efforts.