Reducing lung inflammation in asthma and lung infection by enhancing barrier function through modulation of E-cadherin
Dr. Barry Gumbiner
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.
Dr. Gumbiner is interested in investigating therapeutic candidates for asthma and lung inflammation that function by activating cadherins. Defects in the epithelial barrier function have been observed in inflamed airways and aveoli, with enhanced permeability permitting access of microbes, allergens or toxins into the tissue. E-cadherin has been implicated in airway and aveolar barrier function, and it has been hypothesized that defects in the state of cadherin are involved in disruption or leakiness of the barrier, leading to inflammation. Consequently, it may be possible to slow disease progression in lung inflammation through the enhancement of cadherin activity using activating antibodies that he has developed.
Dr. Gumbiner is interested in industry collaborations focused on validating cadherin-activating compounds for utilization in animal models of lung inflamma¬tion. Ultimately, cadherin activation may also 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
- Preclinical in vivo
- Collaborative research opportunity
- Sponsored research agreement
- Consultation agreement
- Maiden, S.L., Petrova, Y.I., and Gumbiner, B.M. (2016) Microtubules inhibit E-cadherin adhesive activity by maintaining phosphorylated p120-catenin in a colon carcinoma cell model. PLoS ONE 11(2): e0148574. doi:10.1371/journal.pone.0148574. PMCID: PMC4742228
- 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.
To learn more about partnering with Seattle Children’s Research Institute on this or other projects, please contact:
Dr. Elizabeth Aylward, Director
Office of Science-Industry Partnerships
Seattle Children's Research Institute
2001 8th Ave., M/S CW8-5
Seattle, WA 98121