| Research
Interests
The recent
sequencing of the human genome promises to provide numerous
new proteins as drug targets and therapeutic agents.
We are investigating several obstacles to the efficient
commercialization of these delicate molecules.
Because
of the interdisciplinary nature of these challenges,
most projects in our group involve collaborations with
other groups at the University of Virginia, other universities,
and the biotechnology industry.
Molecular
Scale Analysis of Protein Adsorption, Purification,
and Biointerfaces
The structure of proteins can be adversely affected
during manufacturing, purification, formulation and
use in ways that are poorly understood. We use multiple
biophysical experimental techniques as well as molecular
simulation to investigate the structural, kinetic, and
thermodynamic factors important during protein purification.
Currently we are focusing on the challenging case of
hydrophobic interaction chromatography, where many molecular
interactions are at play. We are also developing engineering
planar surfaces with tailored well-defined chemistry
to investigate protein adsorption as well as cell adhesion.
Aggregation
of Protein Biopharmaceuticals and Alzheimer's Disease
Misfolding and association ("aggregation")
can threaten the stability of proteins as pharmaceutical
agents. We are investigating the structural, kinetic,
and thermodynamic features of polypeptide aggregation.
Our goal in this research is to elucidate the mechanisms
of protein aggregation to guide engineering of the solvent
environment and protein molecules themselves to improve
stability. In a similar way, we are also investigating
the aggregation of the amyloid beta peptide, which plays
a central role in Alzheimer's disease.
Selected
Publications
Makrodimitris
K, Fernandez EJ, Woolf T, and O’Connell JP, “Simulation
and Experiment of Temperature and Cosolvent Effects
in Reversed Phase Chromatography of Peptides”,
Biotechnology Progress (2005) 21(3):893-896.
Makrodimitris
K, Fernandez EJ, Woolf T, and O’Connell JP, “ALLD:
An object-oriented mesoscopic simulation program for
polar biomolecules in hydrophobic chromatography or
biomembranes,” Molecular Simulation (2005) 31(9);
623–636.
Mougin
K, Ham AS, Lawrence MB, Fernandez EJ, and Hillier AC,
“Construction of a Tethered Poly(Ethylene Glycol)
Surface Gradient For Studies of Cell Adhesion Kinetics,”
Langmuir (2005) 21(11); 4809-4812.
Makrodimitris,
K; Fernandez EJ; Woolf, T; O’Connell, JP, “Mesoscopic
simulation of adsorption of peptides in a hydrophobic
chromatography system”, Analytical Chemistry (2005),
77(5), 1243-1252.
Stone Olson,
M., Ford, R. M., Smith, J. A., and Fernandez, E. J.,
"Analysis of Column Tortuosity for MnCl2 and Bacterial
Diffusion Using Magnetic Resonance Imaging (MRI)",
Environmental Science and Technology, (2005) 39(1):149-154.
Keener,
R. N., Maneval, J. E., and Fernandez, E. J., "
Toward a Robust Model of Packing and Scale-up for Chromatographic
Beds: 2. Flow compression", Biotechnology Progress
(2004) 20(4):1159-1168.
Keener,
R. N., Maneval, J. E., and Fernandez, E. J., "Toward
a Robust Model of Packing and Scale-up for Chromatographic
Beds: 1. Mechanical compression", Biotechnology
Progress (2004) 20(4):1146-1158.
Stone Olson,
M., Ford, R. M., Smith, J. A., and Fernandez, E. J.,
"Quantification of Bacterial Chemotaxis in Porous
Media Using Magnetic Resonance Imaging (MRI)",
Environmental Science and Technology, (2004) 38 (14)
3864-3870.
Tibbs Jones,
T. and Fernandez, E. J., "Hydrophobic Interaction
Chromatography Selectivity Changes Among Three Stable
Proteins: Conformation Does Not Play a Major Role",
Biotechnology and Bioengineering, (2004) 87 (3):388-399.
Mougin
K, Lawrence MB, Hillier AC, Fernandez EJ, “Construction
of Well-Defined Poly-Ethylene Glycol Self-Assembled
Monolayers on Gold”, Langmuir, (2004) 20 (10):4302-4305.
Tobler,
S.A., Holmes, B. W., Cromwell, M.E., and Fernandez,
E.J., "Benzyl alcohol-induced aggregation of interferon-?:
A study by hydrogen-deuterium isotope exchange",
Journal of Pharmaceutical Sciences, 93 (2004) 1605-1617.
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