Professor and Canada Research Chair in Gap Junctions and Disease
(Cross Appointment with Physiology and Pharmacology)
Ph.D. University of British Columbia
M.Sc. University of British Columbia
B.Sc. University of Prince Edward Island
Our research program is engaged in examining the over two dozen distinct human diseases linked to genes that encode the proteins (connexins) used in gap junctional intercellular communication. Mutations in 50% of the 21 connexin gene family members result in conditions ranging from developmental abnormalities that include hearing loss to life-shortening organ failure. We use a multidimensional approach involving organotypic cultures, genetically-modified mice, connexin-linked disease patient cells, and human inducible pluripotent stem cells to interrogate the scope of mechanisms that lead to disease in some tissues while other organs are spared. Once it is better understood how connexin gene mutations cause diseases and deformities that often intensify in aging, it is anticipated that these findings could be translated to pre-clinical studies and possible treatments of gap junction-linked diseases. In 2005 our program extended to the interrogation of a second family of channel forming proteins called pannexins which we proceeded to clone, sequence, and characterize. Pannexin expression and functional levels have been linked to over a dozen diseases of varying severity but their causal role(s) in disease onset and progression are only beginning to be understood.
D.W. Laird, C.C. Naus and P.D. Lampe (2017) “SnapShot: Connexins and disease”, Cell 170: 1260-1260e1.
E.R. Press, Q. Shao, J.J. Kelly, K. Chin, A. Alaga and D.W. Laird (2017) “Induction of cell death and gain-of-function properties of connexin26 mutants predict severity of skin disorders and hearing loss” Journal of Biological Chemistry 292: 9721-9732.
K.C. Alaga, M. Crawford, L. Dagnino and D.W. Laird (2017) “Aberrant Cx43 expression and mislocalization in metastatic human melanomas” Journal of Cancer 8: 1123-1128.
J.L. Esseltine, Q. Shao, C. Brooks, J. Sampson, D. Betts, C. Seguin and D.W. Laird (2017) “Connexin43 mutant patient-derived induced pluripotent stem cells exhibit altered differentiation potential” Journal of Bone and Mineral Research 32: 1368-1385. Selected for Journal Cover.
E.R. Press, K.C. Alaga, K. Barr, Q. Shao, F. Bosen, K. Willecke and D.W. Laird (2017) “Disease-linked Cx26S17F promotes volar skin abnormalities and mild wound healing defects in mice” Cell Death and Disease Jun 1;8(6):e2845. doi: 10.1038/cddis.2017.234
Aasen, M. Mesnil, C.C. Naus, P.D. Lampe and D.W. Laird (2016) “Gap junctions and cancer: Communicating for 50 years” Nature Reviews Cancer 16: 775-788. Article selected for cover illustration.
J.J. Kelly, J. Esseltine, Q. Shao, E.W. Jabs, J. Sampson, M. Auranen, D. Bai and D.W. Laird (2016) “Specific functional pathologies of Cx43 mutations associated with oculodentodigital dysplasia” Molecular Biology of the Cell 27: 2172-2185.
J. Esseltine and D.W. Laird (2016) “Next-generation connexin and pannexin biology” Trends in Cell Biology 26: 944-955.
J.M. Abitbol, J.J. Kelly, K. Barr, A. Schormans, D.W. Laird* and B.L. Allman* (2016) “Differential effects of pannexins in noise-induced hearing loss” Biochemical Journal 473: 4665-4680. *Co-senior authors
M.K.G. Stewart, J.F. Bechberger, I. Welch, C.C. Naus and D. W. Laird (2015) “Cx26 knockdown predisposes the mammary gland to primary mammary tumors in a DMBA-induced mouse model of breast cancer” Oncotarget 6: 37185-37199.
J.J. Kelly, Q. Shao, D.J. Jagger and D.W. Laird (2015) “Cx30 exhibits unique characteristics including a long half-life when assembled into gap junctions” Journal of Cell Science 128: 3947-3960. Highlighted “In this Issue”
J.L. Esseltine, Q. Shao, T. Huang, J.J. Kelly, J. Sampson and D.W. Laird (2015) “Manipulating Cx43 expression triggers gene reprogramming events in dermal fibroblasts from oculodentodigital dysplasia patients” Biochemical Journal 472: 55-69.
P. Moon, S. Penuela, K. Barr, C.L. Pin, I. Welch, M. Attur, S.B. Abramson, D.W. Laird* and F. Beier* (2015) “Cartilage-specific deletion of Panx3 prevents the development of surgically induced osteoarthritis” Journal of Molecular Medicine 93:845-856. *Co-senior authors.