Dr. Bruce Nicholson's lab studies the coordination of cell behavior though the
direct intercellular exchange of signals via gap junction channels, and the
role they play in several different diseases (including cancer, infection,
deafness and endometriosis).
Specifically, we have been defining the
permeability characteristics of these channels to natural metabolites, including
larger signaling molecules previously thought not to pass through these
channels, like peptides and miRNAs.
We have also been mapping the molecular
determinants that control the gating of these channels, and the pore lining
residues that define their surprisingly selective permeabilities. More
translational aspects of our work include the screening for therapeutics that
can modulate gap junction function, and mouse models where we study the
mechanisms by which gap junctions inhibit metastasis, and promote spread of
inflammatory responses to infection and endometriosis.
Chandrasekhar A, Kalmykov EA, Polusani SR, Mathis SA, Zucker SN, Nicholson BJ. Intercellular redistribution of cAMP underlies selective suppression of cancer cell growth by connexin26. PLoS One. 2013 Dec 3;8(12):e82335.
Ren Q, Riquelme MA, Xu J, Yan X, Nicholson BJ, Gu S, Jiang JX. Cataract-causing mutation of human connexin 46 impairs gap junction, but increases hemichannel function and cell death. PLoS One. 2013 Sep 3;8(9):e74732.
Chaston DJ, Baillie BK, Grayson TH, Courjaret RJ, Heisler JM, Lau KA, Machaca K, Nicholson BJ, Ashton A, Matthaei KI, Hill CE. Polymorphism in endothelial connexin40 enhances sensitivity to intraluminal pressure and increases arterial stiffness. Arterioscler Thromb Vasc Biol. 2013 May;33(5):962-70.
Manam S, Nicholson BJ, Murthy AK. OT-1 mice display minimal upper genital tract pathology following primary intravaginal Chlamydia muridarum infection. Pathog Dis. 2013 Apr;67(3):221-4.
Xu J, Nicholson BJ. The role of connexins in ear and skin physiology - functional insights from disease-associated mutations. Biochim Biophys Acta. 2013 Jan;1828(1):167-78.