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Thomas W. White, Ph.D., Professor
Department of Physiology & Biophysics
School of Medicine, Stony Brook University
Overview:
CONNEXINS
Our research focuses on the intercellular communication provided by gap junction channels, how it is regulated by intracellular signaling cascades, and the human diseases that result from mutations in the genes encoding both the gap junction proteins, called connexins (Cx), and the signaling molecules that regulate their channel activity. Gap junctional communication plays important roles in many aspects of tissue homeostasis, a view supported by the association of connexin mutations with many human genetic diseases such as deafness, skin diseases and cataracts. Our general approach has been to study the consequences of disease causing mutations on the functional behavior of gap junction channels using in vitro assays of channel permeation and gating followed by the generation of genetically engineered mice where genes have been deleted or mutated to create models of human disease.
GAP JUNCTION COMMUNICATION
Connexin proteins (red) are found at the interfaces between epithelial cells (nuclei are blue).
Gap junctions allow cells to directly share small molecules like the fluorescent dye (green) injected into a single central cell that rapidly diffuses into neighboring cells through connexin channels present in gap junctions (cell nuclei are blue).
Current Projects:
A transgenic mouse model of Keratitis Ichthyosis Deafness (KID) syndrome (caused by mutations in Cx26).
A transgenic mouse model of cataract associated with PTEN hamartoma tumor syndrome (PHTS).
Further Reading:
C. Sellitto and T.W. White (2025). Combinatorial genetic manipulation of Cx50, PI3K and PTEN alters postnatal mouse lens growth and homeostasis. Front. Ophthalmol. 5:1502836.
F. Mammano, A.S. Paller and T.W. White (2024). Connexin hemichannel inhibition and human genodermatoses. J. Invest. Derm. doi:10.1016/j.jid.2024.08.003
X. Pan, E.R. Muir, C. Sellitto, Z. Jiang, P.J. Donaldson and T.W. White (2024). Connexin 50 influences the physiological optics of the in vivo mouse lens. Invest. Ophthalmol. Vis. Sci. 65(8):19. https://doi.org/10.1167/iovs.65.8.19
A.A. Giannone, C. Sellitto, B. Rosati, D. McKinnon and T.W. White (2023). Single cell RNA sequencing analysis of the early postnatal mouse lens epithelium. Invest. Ophthalmol. Vis. Sci. 64:37
C. Peres, C. Sellitto, C. Nardin, S. Putti, T. Orsini, F. Scavizzi, M. Raspa, F. Zonta, G. Yang, T.W. White and F. Mammano (2023). Antibody gene transfer treatment drastically improves epidermal pathology in a keratitis ichthyosis deafness syndrome model using male mice. eBioMedicine 89:104453 (full text)
C. Sellitto, L. Li and T.W. White (2022). Double deletion of PI3K and PTEN modifies lens postnatal growth and homeostasis. Cells. 11: 2708
C. Sellitto, L. Li and T.W. White (2021). Connexin hemichannel inhibition ameliorates epidermal pathology in a mouse model of keratitis ichthyosis deafness syndrome. Sci. Rep. 11:24118 (full text)
V. Valiunas and T.W. White (2020). Connexin43 and connexin50 channels exhibit different permeability to the second messenger inositol triphosphate. Sci. Rep. 10:8744 (full text)
Y. Chen, J. Gao, L. Li, C. Sellitto, R.T. Mathias, P.J. Donaldson and T.W. White (2019). The ciliary muscle and zonules of Zinn modulate lens intracellular hydrostatic pressure through Transient Receptor Potential Vanilloid channels. Invest. Ophthalmol. Vis. Sci. 60:4416-4424
V. Valiunas, P.R. Brink and T.W. White (2019). Lens connexin channels have differential permeability to the second messenger cAMP. Invest. Ophthalmol. Vis. Sci. 60:3821-3829
M. Srinivas, T.F. Jannace, A.G. Cocozzelli, L. Li, N. Slavi, C. Sellitto, T.W. White (2019). Connexin43 mutations linked to skin disease have augmented hemichannel activity Sci. Rep. 9:19 (full text)
C. Sellitto, L. Li, E. Vaghefi, P.J. Donaldson, R.Z. Lin and T.W. White (2016). The phosphoinositide 3-kinase p110α catalytic subunit is required for normal lens growth. Invest. Ophthalmol. Vis. Sci. 57:3145-3151
Z. Shuja, L. Li, S. Gupta, G. Meşe, and T.W. White (2016). Connexin26 mutations causing palmoplantar keratoderma and deafness interact with connexin43, modifying gap junction and hemichannel properties. J. Invest. Derm. 136:225-235
C. Sellitto, L. Li, J. Gao, M.L. Robinson, R.Z. Lin, R.T. Mathias and T.W. White (2013). AKT activation promotes PTEN hamartoma tumor syndrome-associated cataract development. J. Clin. Invest. 123:5401–5409
G. Meşe, C. Sellitto, L. Li, H.-Z. Wang, V. Valiunas, G. Richard, P.R. Brink and T.W. White (2011). The Cx26-G45E mutation displays increased hemichannel activity in a mouse model of the lethal form of keratitis-ichthyosis-deafness syndrome. Mol. Biol. Cell 22:4776-4786
F.J. Martinez-Wittinghan, C. Sellitto, L. Li, X. Gong, P.R. Brink, R.T. Mathias and T.W. White (2003). Dominant cataracts result from incongruous mixing of wild-type lens connexins. J. Cell Biol. 161: 969-978
T.W. White (2002). Unique and redundant connexin contributions to lens development. Science 295:319-320 (full text)
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