Rutgers University Department of Molecular Biology and Biochemistry

Stephen Anderson, Ph.D.

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Dept. of Molecular Biology and Biochemistry
Rutgers University
CABM, Room 206
679 Hoes Lane
Piscataway, NJ 08854
(732) 235-5022
fax: (732) 235-5318

Research Summary
Our laboratory is focusing on the study of protein folding and molecular recognition and we are particularly interested in the role these processes may play in the pathophysiology of Alzheimer's disease.

We are using bovine pancreatic trypsin inhibitor (BPTI) as a model system for the protein folding studies. BPTI is a small, globular, 58 amino acid polypeptide and our approach has been to express a recombinant gene for this inhibitor in E. coli and produce, via site-directed mutagenesis, mutants of BPTI having perturbed folding. The folding of these mutants is then characterized in vitro in terms of the thermodynamics and kinetics of the process.

Our work on molecular recognition has centered on the well-characterized protease-protease inhibitor interaction. The specific model system we have employed is the interaction of avian ovomucoid third domains (OM3D) with members of the trypsin family of serine proteases. Our approach is similar to that described above with BPTI, namely the expression of recombinant OM3D in E. coli and specific mutagenesis of reactive site residues. Mutant inhibitors are then tested for binding affinity with a panel of serine proteases. Investigations of the physiological roles that such inhibitors play in vivo are also ongoing.

The Alzheimer's b amyloid precursor protein (APP) is a large, membrane-bound glycoprotein that is expressed in the body from several different alternatively-spliced mRNAs. Contained within this precursor is the amyloid ß peptide which has been strongly implicated as a causal agent in Alzheimer's disease. Our laboratory is currently using a protein engineering strategy to dissect the structure and function of the APP molecule as well as its component domains. We are also seeking to identify and isolate other proteins in the body that bind to APP. By characterizing these features of APP biology we hope to illuminate its role in both normal and diseased tissue.