Faculty > Andley

Usha P. Andley, Ph.D.

 

Associate Professor, Ophthalmology and Visual Sciences
Assistant Professor, Biochemistry and Molecular Biophysics
(314) 362-7167

B.Sc. Chemistry, Delhi University, Delhi, India (1970); M.Sc. Chemistry, Delhi University, Delhi, India (1972); Ph.D. Biochemistry, Jawaharlal Nehru University, New Delhi, India (1977); Fellow, Biochemistry of the Eye, Harvard Medical School (1977-1979)

Research Area:

Cataract

Research Interests:

Molecular biology of lens epithelial cells and stress proteins

My laboratory studies the biochemical basis of human cataract formation. Several approaches are being used at understanding the function of a-crystallin, a major protein of the lens and a member of the small heat shock protein family of molecular chaperones. This protein, composed of two gene products aA and aB, plays important roles in the lens and other tissues. Mutations in aA and aB-crystallins form the basis of several hereditary cataracts. The laboratory is using gene transfer and knockout models to understand the function of a-crystallin in the lens epithelium. Previously it was thought that aA acted simply as a sink for unfolding proteins in lens fiber cells. However, recent work showed that lens epithelial cultures of aA knockout mice have vastly slower growth and an altered cell cycle distribution, and these findings may explain why the aA null lenses are smaller than controls. It was also found that lens epithelial cells derived from aB null mice transform at a higher rate and demonstrate very much increased proliferation and genomic instability. These new finding indicate that aA and aB may be involved in changing the regulation of the cell cycle. Studies now focus on visualizing DNA synthesizing cells in vivo in the aA and aB knockout mice, and to examine the interaction of aA and aB with cell cycle proteins. These studies use confocal microscopy, flow cytometric and biochemical techniques to study the role of a-crystallin in the cell cycle. Genes encoding GFP-tagged a-crystallin are being introduced into lens epithelial cells. Time-lapse video microscopy can then be used to visualize the protein in living cells. Other studies focus on the role of aA in the cross talk between cell proliferation and apoptosis in the lens epithelium.

In a related project, my laboratory is examining the protective phenotype conferred by the expression of this protein in lens epithelial cells, and the effect of specific mutations associated with hereditary cataract on the protective function of a-crystallin. Ongoing studies on the mechanisms of cataract formation are also being pursued through gene chip microarray studies.

Selected Publications:

  1. Bai F, Xi JH, Wawrousek, EF, Fleming TP, Andley UP. Hyperproliferationand p53 status of lens epithelial cells derived from aB-crystallin knockout mice. J Biol Chem 2003 278:36876-36886
  2. Mackay DS, Andley, UP, Sheils A. Cell death triggered by a novel mutation in the aA-crystallin gene underlies autosomal dominant cataract linked to chromosome 21q. Eur J Hum Genet 2003 11:784-793
  3. Xi JH, Farjo R, Ker, TS, Swaroop A, Andley UP. A comprehensive analysis of the expression of crystallin genes in mouse retinas. Mol Vis 2003 9:410-419.
  4. Xi JH, Bai F, Andley UA. Reduced survival of lens epithelial cells in the aA-crystallin knockout mouse. J Cell Sci 2003 116:1076-1085.


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