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View Annual Report - Jules Stein Eye Institute

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suraj P. Bhat, PhD<br />

Associate Professor of Ophthalmology<br />

Member of the <strong>Jules</strong> <strong>Stein</strong> <strong>Eye</strong> <strong>Institute</strong><br />

Member of the Molecular Biology <strong>Institute</strong><br />

ReseaRch summaRy<br />

Molecular Biology of Vision<br />

Dr. Bhat’s laboratory studies the regulation of gene<br />

activity during differentiation and development of the<br />

vertebrate eye. This involves isolation and characterization<br />

of genes and gene products, identification of the<br />

regulatory elements and factors, and elucidation of their<br />

mechanisms employing both in vivo and in vitro paradigms<br />

with manipulated gene sequences.<br />

Two areas of research currently under investigation<br />

are focused on gaining deeper insight into molecular<br />

mechanisms that developmentally predispose the eye to<br />

visual impairment through ocular lens pathologies such<br />

as cataracts, and through retinal diseases including<br />

age-related macular degeneration (AMD).<br />

One area of attention is the study of the developmental<br />

and tissue-specific control of the heat shock promoter<br />

of the αB-crystallin gene and its involvement in cataractogenesis.<br />

Another is the elucidation of the physiological<br />

function of the αB-crystallin protein in the ocular<br />

lens, in the neuroretina and retinal pigment epithelium<br />

(RPE), and in the brain. Technically this work involves<br />

gene manipulations and the study of their consequences<br />

on the phenotype, both in vitro (cultured cells) as well as<br />

in vivo (transgenic animals).<br />

Studies on the regulation of the expression of the small<br />

heat shock protein gene, αB-crystallin are focused<br />

on heat-shock transcription factor 4 (HSF4), which<br />

Dr. Bhat’s laboratory has reported to be the predominant<br />

heat shock transcription factor of the developing<br />

ocular lens and whose post-natal expression correlates<br />

with the most prevalent form of early childhood lamellar<br />

cataracts. Dr. Bhat’s laboratory has generated mouse<br />

models of this cataract, thus enabling first-time investigation<br />

of this childhood pathology.<br />

Studies on the function of the αB-crystallin protein in<br />

the lens and the RPE (in particular its relation to AMD)<br />

are focused on elucidating its “noncrystallin” function,<br />

which is relevant both in the transparent and nontransparent<br />

physiology. These investigations in Dr. Bhat’s<br />

laboratory have led to the discovery of the secretion<br />

of αB-crystallin from the RPE in lipoprotein vesicles<br />

known as exosomes, and initiated studies on<br />

elucidation of intercellular communication (via<br />

exosomes) in the RPE, in health, and in disease.<br />

Public Service<br />

Member, Joint Working Group INDO-US Collaboration in<br />

Vision Research<br />

Assessor, National Health and Medical Research Council,<br />

Australia<br />

Editor, Molecular Vision<br />

Editorial Board Member, Developmental Neuroscience<br />

Editorial Board Member, International Journal of Biochemistry<br />

and Molecular Biology, e-Century Publishing Corporation, USA<br />

Reviewer for many scientific journals<br />

Faculty | Bhat 29

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