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Theodore W. Randolph

Gillespie Professor

Center for Pharmaceutical Biotechnology, Co-Director

ECCH 116

(303) 492-4776
theodore.randolph@colorado.edu

http://www.colorado.edu/che/RandolphGroup

Education:

B.S., University of Colorado (1983)
Ph.D. University of California, Berkeley (1987)

Awards:

• Bioscience Company of the Year - BaroFold, Inc., co-founded by Ted Randolph
• American Society of Engineering Educators Dow Lectureship Award, 2007
• Editorial Board Member  J. Pharmaceutical Innovation
• Ebert Award, Best Original Investigation in 2006, American Pharmacists Association
• American Institute of Chemical Engineers, Professional Progress Award, 2005
• Boulder Faculty Assembly Research and Creative Work Award 2003
• College of Engineering and Applied Sciences Max Peters Award for Outstanding Service 2002
• Editorial Board Member, Journal of Pharmaceutical Sciences
• Outstanding Graduate Teaching Award, Department of Chemical Engineering, 2000
• Editorial Board Member, Current Pharmaceutical Biotechnology
• College of Engineering and Applied Sciences Outstanding Research and Service Award, 1998
• Invited Foreign Researcher, Japanese Agency of Industrial Science and Technology, 1995
• Patten Associate Professor Chair in Chemical Engineering, University of Colorado, Boulder, 1993
• John J. Lee Junior Professorship Chair in Chemical Engineering, Yale University, 1993
• Senior Faculty Fellowship, Yale University, 1993
• NSF Presidential Young Investigator Award (1991)

Katayama, DS, Carpenter, JF, Manning, MC, Randolph, TW, Setlow, P, and Menard KP, (2008) “Characterization of amorphous solids with weak glass transitions using high ramp rate differential scanning calorimetry” Journal of Pharmaceutical Sciences Volume 97, Issue 2.

Seefeldt MB, Crouch C, Kendrick B, Carpenter, JF, and Randolph, TW (2007) “Specific volume and adiabatic compressibility measurements of native and aggregated recombinant human interleukin-1 receptor antagonist: Density differences enable pressure-modulated refolding” BIOTECHNOLOGY AND BIOENGINEERING 98 (2): 476-485 OCT 1 2007.

Thirumangalathu, R, Krishnan, S, Bondarenko, P, Speed-Ricci, M, Randolph, TW, Christians, U, (2007) “Oxidation of methionine residues in recombinant human interleukin-1 receptor antagonist: Implications of conformational stability on protein oxidation kinetics”  Biochemistry 46 (21): 6213-6224.

Randolph, TW and Carpenter, JF (2007) “Engineering challenges of protein formulations,” AIChE J, 53(8), 1902-1907.

Downey, C. D.; Crisman, R. L.; Randolph, T. W.; Pardi, A. (2007) “Influence of Hydrostatic Pressure and Cosolutes on RNA Tertiary Structure” J. Am. Chem. Soc. 129(30); 9290-9291.      

Ng KY, Zhou HY, Zhang YL, Hybertson B, Randolph T, Christians U (2007). Quantification of isoniazid and acetylisoniazid in rat plasma and alveolar macrophages by liquid chromatography-tandem mass spectrometry with on-line extraction. Journal Of Chromatography B-Analytical Technologies In The Biomedical And Life Sciences  847(2):188-198.

Vessely, C., Estey, T, Randolph, TW, Henderson, I, Nayar, R., and Carpenter, JF, (2007) “Effects of Solution Conditions and Surface Chemistry on the Adsorption of Three Recombinant Botulinum Neurotoxin Antigens to Aluminum Salt Adjuvants”, J. Pharmaceutical Science, Journal of Pharmaceutical Sciences,  Volume 96, Issue 9, 2375-2389

Gabrielson JP, Brader ML, Pekar AH, Mathis KB, Winter G, Carpenter JF, Randolph TW. (2007) “Quantitation of aggregate levels in a recombinant humanized monoclonal antibody formulation by size-exclusion chromatography, asymmetrical flow field flow fractionation, and sedimentation velocity”. J Pharm Sci. 2007 Feb;96(2):268-79.

Gabrielson JP, Randolph TW, Kendrick BS, Stoner MR (2007) “Sedimentation velocity analytical ultracentrifugation and SEDFIT/c(s): Limits of quantitation for a monoclonal antibody system”.  Anal. Biochem. Feb 1;361(1):24-30. Epub 2006 Nov 28. 

Research Interests:

Supercritical Fluid Engineering: The use of supercritical fluids in industry is being propelled by regulatory forces (fluids like CO₂ are non-toxic and environmentally friendly), and in addition supercritical fluids offer a unique milieu for both extraction and reaction processes. Our group works on understanding how the unique transport and physical properties of supercritical fluids can be used to develop new applications for supercritical fluids. One example is our new supercritical fluid antisolvent process for forming inhalable, submicron-sized bioerodable polymers for controlled release of pharmaceutical products for tuberculosis therapy and prophylaxis. In collaboration with scientists at the University of Colorado Health Sciences Center and the Colorado State University School of Veterinary Medicine, we are testing controlled release preparations in animal models.

Protein-Solvent Interactions: If a protein is to be used as a therapeutic agent, it must not only be produced in a chemically pure state, but also in a conformationally pure state, and remain so for a reasonable shelf life. Proteins are only marginally stable, and tend to undergo rapid chemical and physical degradation. In addition to developing new protein processing techniques such as high-pressure refolding methods, we are studying the mechanisms by which proteins degrade during processing and storage, and the mechanisms by which various protective agents work to inhibit such damage during processes such as lyophilization, spray-drying, microencapsulation, and storage. We approach the problems by studying the thermodynamics of protein-additive interactions, coupled with spectroscopic characterization of protein chemical and conformational states. To probe experimentally the interaction of proteins with excipients, we use an array of analytical tools. For example, in our recent work investigating the interactions of nonionic surfactants with recombinant human growth hormone, we used electron paramagnetic resonance, Fourier transform infrared, circular dichroism, light scattering, surface plasmon resonance, and fluorescence spectroscopies combined with analytical ultracentrifugation, differential scanning calorimetry, and titration microcalorimetry. To generalize and extend the validity of our work, we turn to solution thermodynamic theories for guidance. As an example, we have been using McMillan-Mayer theory combined with osmotic virial coefficients measured by light scattering to predict the effect of excipients on protein chemical potentials and the subsequent stability of the protein.