A central goal in the field of proteomics is the
discovery of specific protein biomarkers for different disease states.
Most such efforts are focused on mining the serum proteome for such
markers, often through the separation of serum proteins by various
chromatographic means followed by massively parallel analysis by
mass spectrometry. The hope is to identify proteins whose level and/or
post-translational modification state is characteristically altered
in a particular disease state.
A central goal of Dr. Reddy Moola, Prof. Tom Kodadek
and co-workers in the Center is to develop a technique for the identification
of IgG antibody biomarkers for different diseases. Ultimately, we
hope to apply this approach to the identification of narcolepsy-specific
antibodies. Mass spectrometry is poorly suited for antibody analysis,
since IgG antibodies differ from one another by only a small number
of amino acid residues in the antigen-binding region. The method
being explored by UT Southwestern Center researchers involves hybridization
of crude, diluted serum to microarrays comprised ouf thousands of
peptoids. The hope is that different antibodies will bind to specific
peptoids on the array by chance, forming a unique “molecular fingerprint”
as has been observed with other, non-IgG proteins. Thus, if a particular
antibody were highly amplified in a particular disease state to which
the immune system responds, a larger amount of that particular IgG
molecule would bind to particular peptoid spots, providing a specific
biomarker for that disease state. Unpublished studies in the Center
suggest that this approach is indeed a fruitful approach to the identification
of useful antibody biomarkers.
