Leadership Distinguished Lecture Series: “Body-on-a-Chip”: A New Approach to Drug Development

Date: 
10/06/2014 - 4:00pm
Speaker: 
Michael L. Shuler, Ph.D., Samuel Eckert Professor of Chemical Engineering & Biomedical Engineering, Cornell University
Location: 
Communicore, Room C1-15

Abstract:

The current drug development process is costly (> 1 billion dollars) and requires considerable effort (ca. 12 to 15 yrs). Currently, only one in ten drugs entering human clinical trials becomes an approved product. Animal testing is lengthy and costly and the results of animal testing are only marginally useful in predicting human response. Development of a human-based in vitro system has the potential to reduce dependency on animal testing and to make better predictions of human response to drugs. Ideally an effective human surrogate would lead to higher rates of success (say 1 in 4 drug candidates making it to approval) and by reducing the dependency on animals, the process could be accelerated.

Our efforts (1, 2) to construct human surrogates uses a combination of cell cultures and microfabrication. These devices have been referred to as "Body-On-a-Chip" systems or microphysiological systems. These devices are designed to be physical replicas of a physiologically based pharmacokinetic (PBPK) model where cell cultures or tissue engineered constructs are used to replace the differential equations for each organ compartment in the PBPK. A microfluidic system is used where each compartment is interconnected as they might be in a PBPK model. By using cell cultures in place of equations, interactions of the drug with each tissue and communication between each tissue can be replicated even if the mechanisms are unknown and unexpected and would not be captured in the equation by themselves. 

Construction of a "pumpless" system (3) that might serve as a basis for a larger system (e.g. 10 compartments) will be discussed. Such "chips" should be relatively low cost to construct and have the potential for broad application in drug development or potentially to evaluate the toxicity of chemicals. I will discuss some of the issues in the design, construction and use of such devices.

Brief Bio:

Michael L. Shuler is the Samuel B. Eckert Professor of Engineering in Biomedical Engineering and in the School of Chemical and Biomolecular Engineering at Cornell University, Ithaca, New York. He is currently the director for a NCI funded Physical Sciences-Oncology Center (Center for the Microenvironment and Metastasis). Shuler received both of his degrees in chemical engineering (BS, University of Notre Dame, 1969 and Ph.D., University of Minnesota, 1973) and has been a faculty member at Cornell University since January 1974.  Shuler’s research is focused on biomolecular engineering and includes development of “Body-on-a-Chip” or microphysiological system for testing pharmaceuticals and chemicals for toxicity, creation of production systems for useful compounds, such as paclitaxel from plant cell cultures, and constructions of computer models of cells relating physiological function to genomic structure.  Shuler’s research has helped to lay the foundation for modern biochemical engineering and has led to commercial processes for production of the anticancer agent, Taxol, to tools to produce proteins from recombinant DNA (the “High Five” cell line), to software to support systems biology, such as a model of a minimal bacterial cell, and to devices for drug development (“Body-on-a-Chip”). Shuler and F. Kangi have authored a popular textbook, “Bioprocess Engineering; Basic Concepts”.

He has received numerous national and international awards for his research as well as several teaching awards from Cornell. He has an honorary doctorate from the University of Notre Dame.  He has received the Amgen Award in Biochemical Engineering, as well as the Professional Progress, Food, Pharmaceutical and Bioengineering Division Award, and the Warren K. Lewis Awards from the American Institute of Chemical Engineers. Also, he was the inaugural awardee for the J.E. Bailey Award from the Society for Biological Engineering. He received the Pritzker Award from Biomedical Engineering Society and the Marvin Johnson Award from the American Chemical Society.  Shuler has been elected to membership in the National Academy of Engineering and the American Academy of Arts and Science and is a fellow of numerous other professional societies.

Academic year: