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Charles Cooney, Ph.D.

Department of Chemical Engineering
Professor of Chemical and Biochemical Engineering
Co-Director, Sloan Program on the Pharmaceutical Industry (POPI)
Faculty Director, Deshpande Center for Technological Innovation

Room 56-469B
617-253-3108 (phone)


Ph.D. Biochemical Engineering, 1970
Massachusetts Institute of Technology

Research Summary

The Cooney lab is interested in the processes used to manufacture products in biotechnology and pharmaceutical industries. We use various analytical techniques to measure properties of molecules and biological systems used in these industries and apply computational techniques to predict the behavior of the system on a molecular and system-wide scale.

Biotechnology processes
One major focus of biotechnology is the development of processes to produce large amounts of high-quality recombinant proteins for therapeutic applications. In particular, we are interested in the production of the protein human Alpha-1-antitrypsin from bacterial sources (Escherichia coli). Alpha-1-antitrypsin is a protein, native to the lung that inhibits the activity of elastase. In normal individuals, if lung tissue is damaged due to smoking or disease, elastase destroys the damaged tissue. In individuals without alpha-1-antitrypsin, unchecked degradation by elastase can lead to emphysema and chronic obstructive pulmonary disease. Current therapeutic uses for Alpha-1-antitrypsin include treatment of patients lacking the protein to prevent further damage of lung tissue.

Many therapeutic proteins are manufactured with recombinant methods. A gene encoding a protein is introduced into bacteria such that they will produce large quantities that can be purified for use in patient treatment. We are interested in understanding the underlying biology of this process and how growth conditions in the manufacturing procedures affect the final protein product. A powerful analytical tool in this research is transcriptional profiling using DNA microarray technology. We can use transcriptional profiling to understand the pathways affected by introduction and expression of large quantities of a foreign protein. With that understanding, we can design improved methods for therapeutic protein production.

Pharmaceutical processes
Eighty percent of the drugs that are used today are produced as dry powders. However, the science underlying the formation of these powders is very poorly understood. For example, it is difficult, yet very important to mix an active pharmaceutical ingredient (API) with other ingredients like sugar such that each resultant tablet has the exact same amount of API. To investigate the principles behind this process, in collaboration with Prof. Christine Ortiz, we are using atomic force microscopy to measure the cohesive and frictional forces of interactions between particles. For these 20-30 micron particles, we can determine cohesive forces from perpendicular interactions and frictional forces from lateral interactions and use computational techniques, such as DEM (discrete element methods) to simulate large numbers, e.g. 100,000 particles in a blender. With this information, we can predict how the blender is going to perform depending on the physical and chemical properties of the particles that are present. As a systems approach to pharmaceutical powders, we are combining molecular information with computational algorithms to create predictive models that we can then test experimentally.

Selected Publications

  • Lai C.K., D. Holt, J.C. Leung, C.L. Cooney, G.K. Raju and Hansen P. (2001). Real time and noninvasive monitoring of dry powder blend homogeneity. AIChE Journal 47, 2618-2622.
  • Griffiths, S. W. and C. L. Cooney (2002). Development of a peptide mapping procedure to identify and quantify methionine oxidation in recombinant human alpha1-antitrypsin, Journal of Chromatography A., 942, 133-143.
  • Grovender, E.A., C.L. Cooney, R. Langer, and G.A. Ameer, (2002). Immunoadsorption Model for a Novel Fluidized-Bed Blood Detoxification Device. AIChe Journal 48, 2357-2365.
  • Griffiths S.W., King J, Cooney C. L. The reactivity and oxidation pathway of cysteine 232 in recombinant human alpha 1-antitrypsin J BIOL CHEM 277 (28): 25486-25492 JUL 12 2002.
  • Griffiths SW, Cooney C. L. Relationship between protein structure and methionine oxidation in recombinant human alpha 1-antitrypsin BIOCHEMISTRY-US 41 (20): 6245-6252 MAY 21 2002.

Last Updated: April 16, 2008