C. RUSSELL MIDDAUGH

Takeru and Aya Higuchi Distinguished Professor

B.S., 1973, University of California, Santa Cruz; Ph.D., 1978, Cornell University; Postdoctoral Fellow, 1978, University of Minnesota.

Office: B051 Smissman Laboratories
Phone: (785)864-5813
FAX: (785)864-5736
middaugh@ku.edu

Proteins, gene therapy, biophysical chemistry, formulation, delivery, vaccines

Research Interests

The majority of our research focuses in three areas. The first involves the development of vehicles to deliver polynucleotides for gene therapy. To this end, we are: (a) exploring the use of physical methods such as infrared spectroscopy, circular dichroism, fluorescence, light-scattering, calorimetry and related techniques to characterize viral and nonviral gene delivery complexes, (b) studying the cellular barriers to vehicle transport and (c) preparing novel gene delivery systems.

The second area involves studies of proteins that transport across cellular barriers by currently unknown mechanisms. These efforts involve investigations of the structure, stability and membrane activity of a wide variety of proteins of pharmaceutical interest including growth factors and Factor VIII.

The other major area of interest is vaccines. We are currently exploring structural aspects of the delivery of both proteins and polynucleotides as vaccines and the use of adjuvants to enhance immunogenicity in these systems.

Representative Publications

C. M. Wiethoff and C. R. Middaugh, "Barriers to nonviral gene delivery," J. Pharm. Sci., 92: 203–217 (2003).

J. Rexroad, C. M. Wiethoff, A. P. Green, T. D. Kierstead, M. O. Scott and C. R. Middaugh, "Structural stability of adenovirus type 5," J. Pharm. Sci., 92: 665–678 (2003).

L. A. Kueltzo, J. Osiecki, J. Barker, W. L. Picking, B. Ersoy, W. D. Picking and C. R. Middaugh, "Structure-Function Analysis of Invasion Plasmid Antigen C (IpaC) from Shigella flexneri," J. Biol. Chem., 278: 2792–2798 (2003).

S. Choosakoonkriang, C. M. Wiethoff, G. S. Koe, J. G. Koe, T. J. Anchordoquy and C. R. Middaugh, "An infrared spectroscopic study of the effect of hydration on cationic lipid/DNA complexes," J, Pharm. Sci., 92: 115–130 (2003).

C. S. Braun, G. S. Jas, S. Choosakoonkriang, G. S. Koe, J. G. Smith and C. R. Middaugh, "The Structure of DNA within Cationic Lipid/DNA Complexes," Biophys. J., 84: 1114–1123 (2003).

D. T. Brandau, L. S. Jones, C. M. Wiethoff, J. Rexroad and C. R. Middaugh, "Thermal stability of vaccines," J. Pharm. Sci., 92: 218–231 (2003).

C. M. Wiethoff, M. L. Gill, G. S. Koe, J. G. Koe and C. R. Middaugh, "The structural organization of cationic lipid-DNA complexes," J. Biol. Chem., 277: 44980–44987 (2002).

D. B. Volkin, G. Sanyal, C. J. Burke and C. R. Middaugh, "Preformulation studies as an essential guide to formulation development and manufacture of protein pharmaceuticals," Pharm. Biotechnol., 14: 1–46 (2002).

S. A. Tatulian, B. Chen, J. Li, S. Negash, C. R. Middaugh, D. J. Bigelow and T. C. Squier, "The inhibitory action of phospholamban involves stabilization of alpha- helices within the Ca-ATPase," Biochemistry, 41: 741–751 (2002).

P. O. Souillac, H. R. Costantino, C. R. Middaugh and J. H. Rytting, "Investigation of protein/carbohydrate interactions in the dried state. 1. Calorimetric studies," J. Pharm. Sci., 91: 206–216 (2002).

P. O. Souillac, C. R. Middaugh and J. H. Rytting, "Investigation of protein/carbohydrate interactions in the dried state. 2. Diffuse reflectance FTIR studies," Int. J. Pharm., 235: 207–218 (2002).

D. S. Maclean, Q. Qian and C. R. Middaugh, "Stabilization of proteins by low molecular weight multi-ions," J. Pharm. Sci., 91: 2220–2229 (2002).

B. A. Lobo, S. A. Rogers, S. Choosakoonkriang, J. G. Smith, G. Koe and C. R. Middaugh, "Differential scanning calorimetric studies of the thermal stability of plasmid DNA complexed with cationic lipids and polymers," J. Pharm. Sci., 91: 454–466 (2002).

C. Y. Huang, S. S. Ma, S. Lee, R. Radhakrishnan, C. S. Braun, S. Choosakoonkriang, C. M. Wiethoff, B. A. Lobo and C. R. Middaugh, "Enhancements in gene expression by the choice of plasmid DNA formulations containing neutral polymeric excipients," J. Pharm. Sci., 91: 1371–1381 (2002).