Professor of Medicine and
Adjunct Professor of Pathology and Dentistry
B.A. University of California, Irvine
Ph.D. University of Utah
Lorise Gahring's Lab Page
Lorise Gahring's PubMed Literature Search
Molecular Biology Program
Neuroimmune Interactions, Neuroimmunology, neuroinflammation and cytokines
The nicotinic acetylcholine receptor alpha7 (α7) subtype is well-recognized to modulate both central and peripheral neurotransmission, but it also modifies inflammatory processes. In part, the modulatory control by α7 on the inflammatory response is through expression of this receptor on non-neuronal cells such as immune cells and epithelium. A unique property of nicotinic α7 includes its exceptional permeability to calcium, which is sufficient to initiate multiple calcium-mediated intracellular signaling processes. Thus, the broad distribution of α7 expression combined with its significant functional pleiotropy and cell-specific regulation must be considered when defining the contribution of this receptor to the inflammatory process. To facilitate the dissection of how α7 contributes to the organ-specific inflammatory response, we have used a genetic approach to develop new tools to provide us with the specificity and sensitivity for measuring α7 expression by cells in the mouse. Through the precision and specificity of homologous recombination, mice were generated in which a bi-cistronic IRES:tau-GFP reporter cassette (α7G) or an Cre recombinase (α7Cre) are expressed as a 3’ extension to the endogenous α7-transcript. Also, the high permeability of α7 to calcium due to the presence of a glutamic acid at position 260 in the α7 protein has been ablated with minimal impact on the Na+/K+ current through the introduction of a dominant E260A point mutation into α7 (α7E260A:G). These new mouse models dramatically improve the ability to detect and study α7 expression, and they offer the important benefit of doing so while retaining normal genomic context, copy number, and minimal perturbations to normal gene expression and function. Our results combining the use of flow cytometry, RNA-array analysis methods and microscopy are revealing how α7 contributes to multiple steps in an inflammatory response, which includes effects on both cell recruitment and cell signaling responses.
- Enioutina EY, Myers EJ, Tvrdik P, Hoidal JR, Rogers SW, and Gahring LC. 2015. The nicotinic receptor Alpha7 impacts the mouse lung response to LPS through multiple mechanisms. PLoS One. 10(3):e0121128.
- Gahring LC, Enioutina EY, Myers EJ, Spangrude GJ, Efimova OV, Kelley TW, Tvrdik P, Capecchi MR, Rogers SW. 2013. Nicotinic receptor alpha7 expression identifies a novel hematopoietic progenitor lineage. PLoS One. 8(3):e57481.
- Rogers SW, Myers EJ, Gahring LC. 2012. The expression of nicotinic receptor alpha7 during cochlear development.Brain Behav. Sep;2(5):628-39.
- Rogers SW, Tvrdik P, Capecchi MR, Gahring LC. (2012). Prenatal ablation of nicotinic receptor alpha7 cell lineages produces lumbosacral spina bifida the severity of which is modified by choline and nicotine exposure. Am. J. Med. Genet A. 158A(5):1135-44.
- Gahring LC, Osborne AV, Reed M, Rogers SW. 2010 Neuronal nicotinic alpha7 receptors modulate early neutrophil infiltration to sites of skin inflammation.J Neuroinflammation. 7(1):38.
- Osborne-Hereford AV, Rogers SW, Gahring LC. 2008. Neuronal nicotinic alpha7 receptors modulate inflammatory cytokine production in the skin following ultraviolet radiation.J Neuroimmunol. Jan;193(1-2):130-9.
- Gahring LC, Osborne-Hereford AV, Vasquez-Opazo GA, Rogers SW. 2008. Tumor necrosis factor alpha enhances nicotinic receptor up-regulation via a p38MAPK-dependent pathway.J Biol Chem. 11;283(2):693-9.