Roles of gap junctions in excitable and inexcitable cells

Research of our laboratory is centered on physiological and cell/molecular biological studies of gap junctions, the intercellular channels that allow cells to directly exchange ions and metabolites. In the nervous system, gap junctions form electrotonic synapses between neurons, permitting synchronized excitation of coupled cells, and they couple glia into a complex interconnected network where information is exchanged through calcium waves and metabolically. Major projects of the laboratory are attempting to resolve (1) role of gap junctions and extracellular signaling in a mouse model of orofacial pain, (2) how connexin-protein interactions (which result in a dynamic complex that we term the “Nexus”) deliver, assemble and modulate gap junctions in various cell types, (3) the role of gap junctions in stem cell therapy in a mouse model of Chagas disease (with H.B. Tanowitz, Dept Pathology), (4) endothelial cell and astrocyte mechanotransduction and cell polarization in a blood-brain-barrier model (with members of the Biomedical Engineering Department, CCNY).  These studies utilize a variety of preparations, including primary cultures of cells from transgenic mice with altered expression of connexin and other genes and transfection of wildtype and mutated connexin sequences into communication deficient cell lines, where small high resistance cells permit structure-function analysis at the single channel level. Techniques include intracellular recordings with conventional and ion-selective microelectrodes, photomanipulation such as FRAP, optical monitoring of intracellular ionic activities (especially Ca²⁺ and propagated Ca²⁺ waves), patch clamp recording of single channels and whole cell currents and standard molecular biological and immunological methods such as Northern and Western blot analyses, immunostaining and RT-PCR and expression profiling using microarrays.

Representative recent publications (for Pubmed records, see D. Spray)

1. Bejarano E, Yuste A, Patel B, Stout RF Jr, Spray DC, Cuervo AM. Connexins modulate autophagosome biogenesis. Nat Cell Biol. 2014 May;16(5):401-14.
2. Jasmin, Jelicks LA, Tanowitz HB, Peters VM, Mendez-Otero R, Campos de Carvalho AC, Spray DC. Molecular imaging, biodistribution and efficacy of mesenchymal bone marrow cell therapy in a mouse model of Chagas disease. Microbes Infect. 2014 Nov;16(11):923-35.
3. Thi MM, Suadicani SO, Schaffler MB, Weinbaum S, Spray DC. Mechanosensory responses of osteocytes to physiological forces occur along processes and not cell body and require αVβ3 integrin. Proc Natl Acad Sci U S A. 2013 Dec 24;110(52):21012-7.
4. Spray DC, Hanstein R, Lopez-Quintero SV, Stout RF Jr, Suadicani SO, Thi MM. Gap junctions and Bystander Effects: Good Samaritans and executioners. Wiley Interdiscip Rev Membr Transp Signal. 2013 Jan;2(1):1-15.
5. Rozental R, Campos de Carvalho AC. (2000) David Spray and science in Brazil. Brain Res Brain Res Rev. 32:9-10.
6. Adesse D, Goldenberg RC, Fortes FS, Jasmin, Iacobas DA, Iacobas S, Campos de Carvalho AC, de Narareth Meirelles M, Huang H, Soares MB, Tanowitz HB, Garzoni LR, Spray DC. Gap junctions and chagas disease. Adv Parasitol. 2011;76:63-81.
7. Spray DC, Iacobas DA. Organizational principles of the connexin-related brain transcriptome. J Membr Biol. 2007 Aug;218(1-3):39-47.
8. Spray DC, Scemes E and Dermietzel R (2013) Gap Junctions in the Nervous System In: Enclyclopedia of the Neurological Sciences Second Edition, Eds: MJ Aminoff and RB Daroff. Academic Press, in press.
9. Spray DC and Scemes E (2012) Gap Junction Proteins (Connexins, Pannexins, and Innexins). Encyclopedia of Biophysics, Ed: GCK Roberts, Springer-Verlag Berlin, in press.
10. Dermietzel, R. and Spray DC. (2012) Blood-Brain-Barrier and the Neural-Vascular Unit. In Astrocytes: Wiring the Brain, Eds: E. Scemes and DC Spray. Taylor & Francis, CRC Press. Pp. 179-203.
11. Dermietzel R and Spray DC (2012) Gap Junctions and Electrical Synapses In Textbook of Neuroscience in the 21st Century: Basic and Clinical. Heidelberg: Springer Verlag.(2011) Editor-in-Chief: D.W. Pfaff,. In press.
12. Hanani M and Spray DC (2012)Chapter 11. Glial cells in autonomic and sensory ganglia In: Neuroglia. Eds: H. Kettenmann and B. Ransom. Oxford University Press, in press. Pp. 122-133.
13. Dermietzel, R. and Spray, D.C. (Eds) (2012) Electrical synapses: From the lab to the clinic. Brain Research Reviews Special Issue.