Harvey W. Blanch

Research Interests

Biochemical engineering, applied enzymology, bioproduct recovery.

Research Summary

Protein aggregation
The ability to control or reverse protein aggregation is vital to the production and formulation of therapeutic proteins and may be a key to prevention of over 20 neurodegenerative diseases in which aggregation is implicated. Our work incorporates experimental studies and computational treatments aimed at elucidating the molecular mechanisms of aggregation. Our simulation studies include coarse-grained approaches and molecular dynamic studies of small proteins and peptides.

Metabolic EngineeringApplication to Mammalian Cells
We study the growth and metabolism of human breast cancer cells. We quantify the physiological response of breast cancer cells to estrogen, the commonly-employed anti-cancer drug tamoxifen, and cerulenin, which influences fatty acid metabolism. Cells are grown on microcarriers under controlled conditions, and growth rates, glucose uptake, glutamine consumption rates, and other metabolic parameters are observed in estrogen receptor positive (ER+) and ER- cells. Cells are challenged with estrogen and tamoxifen. 

Intracellular metabolic fluxes are determined using 13C-labelled glucose and glutamine, by measuring intracellular fates and concentrations of NMR-observable metabolites. The objectives are to quantitatively determine how metabolism in breast cancer cells differs from that in normal cells, and the role played by estrogen and by anti-cancer drugs. A new approach to analysis of the isotopomer data we obtain has been developed. With flux data available, potential enzymes activities can be identified as targets for drug development.

Selected Publications

Wei Liu, Troy Cellmer, David Keerl, John M. Prausnitz, and Harvey W. Blanch, “Interactions of lysozyme in guanidinium chloride solution from dynamic light scattering measurements” Biotechnology & Bioengineering 90 (4), 482-490 (2005)

Cellmer, Troy, Bratko, Dusan, Prausnitz, John, Blanch, Harvey, “Protein Folding Landscapes in Multichain Systems”, PNAS 102 (33), 11692-11697 (2005)

Voogt, Jason, Blanch, Harvey, “Separation of Polyunsaturated Fatty Acids by Selective Inclusion in Guanidinium-1,5-naphthalenedisulfonate-2-methoxyethanol Networks”, Biotech & Bioeng., 92 (5), 532-540, (2005) [Featured on Cover]

Hsiao, T., Blanch, H.W., “Physiological Study of Polyunsaturated Fatty Acid Production in the Marine Microalga Glossomastix chrysoplasta”, Biotech. Bioeng.,  93(3),  465-475 (2006)

Bratko, D.N, Cellmer, T., Prausnitz, J.M., & H.W. Blanch, “Effect of single-point sequence alterations on the aggregation propensity of a model protein”, JACS, 128 (5), 1683-1691 (2006) 

Forbes, N., Meadows, A., Clark, D.S. & H.W. Blanch, “Estradiol stimulates the biosynthetic pathways of breast cancer cells: detection by metabolic flux analysis” Metabolic Engineering, 8(6), 639-652 (2006)