Inflammatory Bowel Disease – Cadherin-Mediated Interventions
Slowing Disease Progression in IBD Through The Modulation of Cadherin Activity
Cadherin-mediated cell adhesion is a dynamic and tightly regulated process with important implications for development, morphogenesis, and disease. The Gumbiner lab is gaining an understanding of the basic mechanisms of cadherin function and applying this knowledge to disease states associated with deficits in cadherin function. Dr. Gumbiner has shown that cadherins can be physiologically regulated by changes in conformation and/or physical state at the cell surface independent of internalization or catenin dissociation, other mechanisms that have been proposed to control cadherins.
Dr. Gumbiner is interested in investigating therapeutic candidates for IBD that function by activating cadherin pathways. Defects in the intestinal epithelial barrier function have been observed in IBD, with enhanced permeability being an early stage defect that precedes overt inflammation. The E-cadherin gene has been implicated in IBD through genome wide association studies (GWAS), and because cadherins are dynamic components of the barrier, Dr. Gumbiner has hypothesized that defects in cadherin, or the state of cadherin, are involved in disruption or leakiness of the barrier, leading to IBD. Consequently, it may be possible to slow disease progression in IBD through the modulation of cadherin activity.
Dr. Gumbiner would be interested in industry collaborations focused on validating cadherin-activating compounds for utilization in animal models of IBD. Ultimately, cadherin activation may have therapeutic utility in a wide variety of disease, including inflammatory vascular conditions, tumor metastasis, and endothelial dysfunction.
Stage of Development
- Pre-clinical in vitro
- Pre-clinical in vivo
- Collaborative research opportunity
- Sponsored research agreement
- Consultation agreement
- Petrova, Y.I., M.M. Spano, and B.M. Gumbiner, (2012) Conformational epitopes at cadherin calcium- binding sites and p120-catenin phosphorylation regulate cell adhesion. Molec. Biol. Cell. 23:2092-2108. PMCID: PMC3364174
- Gumbiner, B.M. (2005) Regulation of cadherin-mediated adhesion in morphogenesis. Nature Reviews Molecular Cell Biology, 6, 622-634. PMID: 16025097.
- Petrova YI, Schecterson L, Gumbiner BM. Roles for E-cadherin cell surface regulation in cancer. Mol. Biol. Cell. 2016. 27: 3233-3244; doi:10.1091/mbc.E16-01-005.
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