Gerald B. Grunwald, PhD

Contact Dr. Grunwald

1020 Locus Street

Philadelphia, PA 19107

(215) 503-4191
(215) 503-6690 fax

How Do Errors in Cell Interactions and Differentiation Contribute to Ocular Disease?

Development of complex organs such as the eye depends upon highly orchestrated regulatory processes that control the interaction of cells with each other and with their environment. These processes assure the proper development of cells in the embryo as well as their continued normal function in adults. The onset of ocular diseases that can compromise normal visual function may be due in part to malfunctions of these important regulatory pathways.

Our research is thus directed at understanding the role of cadherin cell adhesion molecules and related signaling pathways in the normal development and function of the retinal pigment epithelium (RPE) cells of the eye. These cells are critical for maintaining normal visual function, but in some diseases phenotypic transformation of RPE cells contributes to the onset and progression of ocular proliferative disorders such as proliferative vitreoretinopathy (PVR). The formation of epiretinal membranes in PVR which impair normal ocular function may involve an epithelial-mesenchymal transformation (EMT) of RPE cells as part of an aberrant wound healing response. While the underlying mechanism remains unclear, this includes changes in RPE cell gene expression under the control of specific transcription factors and alterations of normal cell-cell interactions.

Currently our studies are directed at identification of the mechanisms that regulate EMT in RPE cells. To accomplish this we utilize in vitro model systems and the tools of modern cell, molecular and computational biology to identify biologically relevant transcription factors and their associated signaling pathways that are likely to regulate RPE cell phenotype and whose malfunctions may produce pathological changes in RPE cells in response to diseases or trauma such as retinal detachment. These molecules and pathways may provide potential therapeutic targets for the prevention and treatment of ocular proliferative disorders such as PVR.

Publications

Most recent Peer-reviewed Publications

1. Microphthalmia-associated transcription factor (MITF) promotes differentiation of human retinal pigment epithelium (RPE) by regulating microRNAs-204/211 expression
2. Modulation of MCT3 expression during wound healing of the retinal pigment epithelium
3. Transcriptional regulatory network analysis during epithelial-mesenchymal transformation of retinal pigment epithelium
4. Cadherins and NCAM as potential targets in metal toxicity
5. N-cadherin function is required for differentiation-dependent cytoskeletal reorganization in lens cells in vitro
6. Differential expression of N- and B-cadherin during lens development
7. Chapter 3 Cadherin Cell adhesion molecules in development and disease
8. In vivo analysis ok in-c adhlr1n cell adhesion molecule function in ocular development using transgenic mice expressing tissue-specific dominant-negative mutations
9. Difkereyiiai. spatio temporal expression paturns of v and b-cadherins correlate with specific morphogenetic events during lens development
10. Evidence that tyrosine phosphorylation regulates N-cadherin turnover during retinal development
11. Fibroblast growth factors are necessary for neural retina but not pigmented epithelium differentiation in chick embryos
12. Discovery and Analysis of the Classical Cadherins
13. Cadherin function is required for axon outgrowth in retinal ganglion cells in vivo
14. Cadherin cell adhesion molecules in retinal development and pathology
15. Ca2+ influx and neurite growth in response to purified N-cadherin and laminin
16. The structural and functional analysis of cadherin calcium-dependent cell adhesion molecules
17. Structure/function analysis of the integrin β1 subunit by epitope mapping
18. Analysis of protein variations in adult and postnatal day 11 staggerer and lurcher mutant mice
19. Purification and characterization of NCAD90, a soluble endogenous form of N-cadherin, which is generated by proteolysis during retinal development and retains adhesive and neurite-promoting function
20. Immunohistochemical and biochemical analysis of N-cadherin expression during CNS development

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