• American Institute of Medical and Biological Engineering, Fellow (2006)
• Van Lanen Award for service to the American Chemical Society, Division of Biochemical Technology (2005)
• NSF Career Young Faculty Development Award
• Rodman Scholars Award (U. Virginia) for Excellence in Teaching (1999)
• University Teaching Fellow (U. Virginia, 1997)

The 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. In addition, we are exploring protein misfolding relating to human disease.

Molecular Analysis of Protein Adsorption and Purification
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.

Misfolding of Pharmaceutical Proteins and Proteins Relevant to Human Disease
Misfolding and association ("aggregation") can threaten the stability of proteins as pharmaceutical agents. 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. Toward this end, we are combining experimental analysis with computational protein design approaches to reduce aggregation. In a similar way, we are also investigating the aggregation of peptides and proteins relevant to human disease (e.g. Alzheimer’s).

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.

Selected Publications

Qi W, Zhang A, Good TA, Fernandez EJ, Osmolyte effects on AB aggregation and oligomer-membrane interactions Biochemistry (2009), in press. [DOI]

Deitcher RW, Gildea PA, Rome JE, Fernandez EJ, O’Connell JP, A new thermodyamic approach to adsorption in hydrophobic interaction chromatography, J. Chromatography A (2009) in press. [DOI]

Salay LC, Qi W, Keshet B, Tamm LK, and Fernandez EJ, “Membrane interactions of a self-assembling model peptide that mimics the self-association, structure and toxicity of Aß(1-40)”, BBA Biomembranes, (2009) in press. [DOI]

Jordan JL, Arndt JW, Hanf K, Li G, Hall J, Demarest S, Huang F, Wu X, Miller B, Glaser S, Fernandez EJ, Wang D, Lugovskoy A., “Structural Understanding of Stabilization Patterns in Engineered Bispecific Ig-Like Antibody Molecules”, Proteins, (2009) in press. [DOI]

Ramos I, Fabris D, Qi W, Fernandez EJ, Good TA, Kinetic Study of Beta-amyloid residue accessibility using Reductive Alkylation and Limited Proteolysis followed by Mass Spectrometry, Biotechnology and Bioengineering, (2009) 104:181-192. [DOI]

Zhang A, Qi W, Good TA, Fernandez EJ, “Structural differences between Aß(1-40) intermediate oligomers and fibrils elucidated by proteolytic fragmentation and H/D exchange”, Biophysical Journal, 96(3):1091-1104 (2009). [DOI]