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Department of Pharmacology
Paul Axelsen, M.D.

Education:

1982

M.D.

Mayo Medical School

Research Summary:

The biophysics of molecular recognition - understanding how bioactive molecules recognize their target sites of action, and how they accomplish their function after binding to their target site. Our investigations are done using computer graphics modeling, molecular dynamics simulation, various forms of optical spectroscopy (infrared and fluorescence), NMR, and x-ray crystallography, with a view towards the rational design of new pharmacological agents for use against infections, malignancies, cardiovascular, and neurological diseases

Research Themes:
Infectious disease (antibiotic pharmacology, antimicrobial peptides,
antibiotic resistance, vancomycin)
Neurodegeneration (amyloid, Alzheimer's disease)
Cardiovascular disease (lipoprotein structure and function)

Focus Areas:
Rational drug design, molecular recognition
Protein-lipid interactions involved in protein folding, misfolding, and
amyloidogenesis
Mechanisms and consequences of oxidative lipid membrane damage

Core Technologies:
Computational chemistry (molecular simulation, molecular graphics)
Internal reflection infrared spectroscopy (supported monolayers)
Fluorescence spectroscopy (steady state, time resolved)
Mass spectrometry (electrospray, triple-quadrupole, ion trap)

Selected Key Publications:

Configurational Entropy and Cooperativity Between Ligand Binding and
Dimerization in Glycopeptide Antibiotics.
Jusuf, S., Loll, P.J., and P. H. Axelsen
Journal of the American Chemical Society 125:3988-3994, 2003.

Structural Analysis of Lipoprotein E Particles
Lumelle A. Schneeweis,
Vishwanath Koppaka, S. Lund-Katz, M. C. Phillips, and P. H. Axelsen
Biochemistry 44:12525-12534, 2005.

Promotion Of Oxidative Lipid Membrane Damage By Amyloid b Proteins.
I.V.J. Murray, M. E. Sindoni, and P. H. Axelsen
Biochemistry 44:12606-12613, 2005.

Membrane Mediated Amyloidogenesis and the Promotion of Oxidative Lipid Damage
by Amyloid beta Proteins.
Murray, I.V.J., Liu, L., Komatsu, H., Uryu, K., Xiao, G., Lawson, J.A., and
Axelsen, P.H.
Journal of Biological Chemistry 282:9335-9345, 2007.

Promotion of Amyloid beta Protein Misfolding and Fibrillogenesis by a Lipid
Oxidation Product.
Liu, L., Komatsu, H., Murray, I.V.J., and Axelsen, P.H.
Journal of Molecular Biology 377:1236-1250, 2008.

Two dimensional infrared spectra of isotopically diluted amyloid fibrils from
Abeta40.
Kim, Y.S., Liu, L., Axelsen, P.H., and Hochstrasser, R.M.
Proceedings of the National Academy of Sciences USA 105:7720-7725, 2008.

Lab Address:

Department of Pharmacology
105 Johnson Pavilion
3620 Hamilton Walk
Philadelphia, PA 19104-6084