Eric T. Boder
Career Development Associate Professor of Chemical and Biomolecular Engineering, University of Tennessee, Knoxville
Adjunct Associate Professor of Chemical and Biomolecular Engineering, University of Pennsylvania
B.S., Chemical Engineering, Washington University, 1993
M.S., Chemical Engineering, University of Illinois, 1996
Ph.D., Chemical Engineering, University of Illinois, 1998
 
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Research Group Home Page
 

Current Focus of Research:

Proteins are naturally occurring polymers comprised of amino acid subunits. The advantage of these molecules is their ability to catalyze a wide range of complex chemistries and engage in countless exquisitely specific molecular interactions, yet each protein is itself constructed from a single synthetic chemistry and its function is perfectly contained within a simple genetic code. The ability of this class of molecule to perform highly complex tasks, combined with their relative ease of synthesis by microorganisms, has spurred the development of an industry pursuing the use of proteins in separations, diagnostics, and numerous medical therapies.

Protein pharmaceuticals, also called biopharmaceuticals, represent a rapidly developing product area in industry. In many cases, the extreme specificity of molecular interations required to inhibit certain disease states has limited the success of small organic pharmaceuticals in treatment. Protein reagents have the potential to overcome this obstacle; however, the utility of proteins as therapeutic agents has been limited by the lack of a quantitative engineering approach to developing proteins with the appropriate molecular properties. My goal is to develop a program of research addressing this need. This research must consider several critical points:

1. Selection of a molecular scaffold with properties suitable for the intended application (e.g, tissue penetration properties, thermal stability).

2. Development of protein engineering processes for quantitatively altering the functional properties of the chosen reagent to optimize for the specific application.

3. Quantitative analysis of the relevant molecular properties and combination of this knowledge with protein engineering processes for molecular design.

A particular target application of this research is engineering the immune response. Numerous devastating diseases result from destruction of the body's own tissues due to attack by the cellular immune system (autoimmunity). Misidentification of self in autoimmunity and immunological attack of transplanted tissues, as well as failure of the immune system to identify certain harmful entities (e.g., certain viruses or tumor cells), is essentially a problem of molecular recognition. Inhibiting undesirable immune responses or stimulating immune responses against novel targets are problems most likely to be solved by taking advantage of the unique properties of engineered protein reagents. Research in this area makes use of tools from molecular biology, protein chemistry, and biophysics.

Selected Publications (more info):

S. Subramanian, E.T. Boder, and D.E. Discher:  Phylogenetic Divergence in Human SIRPa-CD47 Interactions Reveals Locus of Species-specificity: Implications for the Binding Site.  J. Biol. Chem. (in press).

J.H. Lee, M. Goulian, and E.T. Boder:  Autocatalytic Activation of Influenza Hemagglutinin.  J. Mol. Biol., 364:275-282 (2006).

L.R. Pepper, D.A. Hammer, and E.T. Boder: Rolling Adhesion of aL I Domain Mutants Decorrelated from Binding Affinity J. Mol. Biol., 360:37-44 (2006).

S. Park, Y. Xu, X.F. Stowell, F. Gai, J.G. Saven, and E.T. Boder:  Limitations of yeast surface display in engineering proteins of high thermostability.  Prot. Eng. Des. Sel., 19:211-217 (2006).

P. Derr, E. Boder, and M. Goulian:  Genetic selection for new bacterial chemoreceptors. J. Mol. Biol.  355:923-932 (2006).

S. Subramanian, R. Parthasarathy, E.T. Boder, and D.E. Discher:  Species-specific adhesive interactions between CD47 and human SIRPa.  Blood, 107:2548-2556 (2006).

R. Parthasarathy, S. Subramanian, E.T. Boder*, and D.E. Discher:  Post-translational regulation of expression and conformation of an immunoglobulin domain in yeast surface display.  Biotechnol. Bioeng., 93:159-168 (2006).

R. Parthasarathy, J. Bajaj, and E.T. Boder:  Immobilized biotin ligase via surface display of E. coli BirA on Saccharomyces cerevisiae.  Biotechnol. Prog., 21:1627-1631 (2005).

E.T. Boder, J.R. Bill, A.W. Nields, P.C. Marrack, and J.W. Kappler:  Yeast surface display of a noncovalent MHC class II heterodimer complexed with antigenic peptide.  Biotechnol. Bioeng., 92:485-491 (2005).

S. Park, E.T. Boder, and J.G. Saven:  Modulating the DNA affinity of Elk-1 with computationally selected mutations.  J. Mol. Biol., 348:75-83 (2005).

S.J. Park, H. Kono, W. Wang, E.T. Boder, and J.G. Saven: Progress in the development and application of computational methods for probabilistic protein design.  Computers Chem. Eng., 29:407-21 (2005).