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Professor
Biochemistry
Born 1946; B.S. with Honors, University of California, Berkeley, 1968; Ph.D.,
Massachusetts Institute of Technology, 1971; Postdoctoral Fellow, Rice
University, 1971-72; Lecturer, Chinese University of Hong Kong, 1972-1973;
Postdoctoral Fellow, University of Pittsburgh, 1973-1977; Assistant Professor,
Wayne State University, 1977-1982; Associate Professor, Wayne State University,
1982; Associate Professor, Loyola University of Chicago, 1982-1986; Professor,
Loyola University of Chicago, 1986-2004. NIH National Research Service
Award, 1975-1979; NIH Research Career Development Awardee, 1981-1986.
NIH Study Section member (BBCB) 1985 - 1989. American Heart Association
Study Group (CFM) 1999-present.
We study a family of proteins - the spectrin isoforms. Spectrin, a
major protein in the membrane skeleton or cytoskeleton, is believed to
have evolved early in the development of metazoans, following divergence
of fungi, plants and vertebrates, with each isoform representing a candidate
for roles in specialized activities of multicellular animals.
The high degree of sequence homology amongst different spectrin isoforms
suggests similar structures and similar functions for these isoforms.
Yet, at least two of the better studied isoforms, erythroid and brain
spectrins, exhibit quite different affinities in subunit interactions
to form tetramers, which is the functional form for spectrin. The differences
in affinities are probably due to small differences in conformation,
or large differences in conformation of small areas (i.e. specific residue-residue
pairing, kinetic differences in association, etc.). We are using various
biophysical methods and recombinant model peptides of spectrin fragments
to study differences in critical regions of brain and erythroid spectrin
isoforms. The methods include cysteine scanning for spin or fluorescent
labeling, as well as high resolution NMR and X-ray studies. Our
broad, long-term objectives are to understand conformations of critical
regions in various spectrin isoforms and to correlate specific structural
features in these isoforms with functions unique to individual isoforms. Findings
from these studies will provide insight toward developing molecular understanding
of normal physiology involving spectrin molecules in erythrocytes, brain
cells and other types of cells, and of diseases related to spectrin tetramers,
such as hereditary hemolytic anemia blood diseases, and neurological
disorders (e.g., many Alzheimer patients have elevated antibodies toward
brain spectrin fragments).
These studies not only provide information on two important spectrin
isoforms, but may also serve as examples for other highly homologous
proteins with similar general folding patterns, that exhibit small conformational
variations to provide functional differences.
We believe that disease markers and drug targets can be identified
through functional proteomic studies of spectrin isoforms and their protein-protein
interactions.
Top: Molecular shapes/envelopes determined from the measured
SAXS data of SpαI-1-156 (left, erythroid spectrin) and SpαII-1-149
(right, brain spectrin). Bottom left: Ensemble structures for SpαI-1-156
calculated from NMR data; right: model structure for SpαII-1-149.
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