Val Shestopalov, Ph. D.
Dmitry Ivanov, Ph. D.
Galina Dvoriantchikova, Ph. D.
are focused on molecular, cellular and systems
biology of ocular tissues with particular emphasis on the
lens and the retina. We investigate the molecular and cellular mechanisms
underlying pathophysiology of the two most blinding human diseases: cataract
and glaucoma. Cataract formation in the lens and glaucomatous optic neuropathy
are the two most blinding diseases worldwide.
Disrupted communication between fiber cells in the avascular lens tissue results in optical aberrations and cataract formation. We study proteins implicated in several parallel pathways of intercellular communication in the lens. In addition to “classical” connexin-based gap junctions and novel syncytial pathways characterized in our lab few years ago, we recently identified that the third, pannexin-mediated coupling, is also present in the lens. In the year 2004 our lab received a prestigious PECASE Award from the White House for the work on the lens syncytium. Read more…
In human primary open
angle glaucoma (POAG) irreversible damage to the axons occurs at the lamina
cribrosa in the optic nerve head (ONH). In common with many complex diseases,
glaucoma is facilitated by homeostatic imbalance resulting from environmental
factors and multiple genetic components interconnected in complex epistatic
networks. We utilized systems biology approach to analyze and compare the
microarray and the published data and to determine pathways
implicated in pathophysiology of the disease. We detected
several glial cellular pathways potentially relevant to glaucoma in humans.
Complex, multifactorial nature of the both disorders, slow progression and strong influence of age require comprehensive systems approach to study them. We utilize the vast array of modern molecular cell biology, functional genomics and bioinformatics methods to elucidate these mechanisms at the levels of gene regulation, protein interaction and activity of pathways and protein networks. Using the MetaCore™ Analytical suite (in collaboration with GeneGo Inc.) we extract additional layers of functional information from various “high throughput” (HT) data. Analysis of HT data obtained from the affected cells in the lens and the optic nerve tissues revealed changes in complex networks of interacting cellular pathways. Read more…