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Research

Peptide and protein chemistry

Our lab combines biochemistry, biophysics, organic chemistry, virology, and cell biology to study and engineer proteins and peptides for biomedical applications.  We are currently engaged in several active lines of research:

1. Engineering of Novel Virus Immunotherapeutics

There has been much recent interest in the use of monoclonal antibodies (mAbs), or cocktails thereof, for treatment of viral diseases. We are using state-of-the-art protein engineering technologies to develop novel immunotherapeutics against several viruses.  A recent example is the use of "synthetic antibody technology" to develop the first humanized protective mAbs against the Sudan ebolavirus species (see below and ACS Chem. Biol., 2014, 9, 2263), the result of a large multi-institution collaborative effort. Synthetic antibody technology is a phage-based approach that allows the production and screening of very large (> 1010) protein libraries.  There are five species of ebolavirus and, while many potential mAbs are available for the Zaire ebolavirus species, few are available for Sudan ebolavirus despite its high pathogenicity and increasing prevalence.  Subsequent efforts are focused on using nascent protein engineering technologies to address unmet immunotherapeutic needs for this and other viruses.

Figure - Protein engineering of novel, human, protective Sudan ebolavirus antibodies.

2. Mechanisms of Viral Membrane Fusion

Membrane-bound viruses require fusion between the host and viral membranes for infection.  Although the details of the mechanism for membrane fusion differ among viruses, a common conformational state is the "extended" or "prehairpin" intermediate, in which the viral fusion subunit spans both the host and viral membranes.  Collapse of this extended intermediate into a stable hairpin-like structure provides the energetic driving force for membrane fusion.  We are using biophysical and structural methods to dissect fine details of the fusion process (below and: Biochemistry, 2015, 54, 1589; J. Mol. Biol., 2014, 426, 1452; Structure, 2013, 21, 1085 as examples).

Figure - Structural alignment of "post-fusion" hairpin structures of CAS Virus, Marburg virus, Moloney murine leukemia virus, and lymphocytic choriomeningitis virus fusion subunits.

3. Protein Structure and Molecular Recognition

We use combinatorial biochemistry, and traditional biophysical approaches to decipher determinants for protein structure and molecular recognition.  These studies illuminate the requirements for specificity and affinity at intermolecular interfaces and provide new tools and potential therapeutics.

Last Updated on Tuesday, 21 April 2015 21:00