David I. Yule, Ph.D.

David I. Yule, Ph.D.

Contact Information

University of Rochester Medical Center
School of Medicine and Dentistry
601 Elmwood Ave, Box 711
Rochester, NY 14642

Office: (585) 273-2154
Lab: (585) 275-6128
Fax: (585) 273-2652

Research Bio

In exocrine acinar cells regulation of intracellular calcium plays a pivotal role in controlling fluid and protein secretion. Exposure of cells to neurotransmitters and hormones results in a rapid elevation of intracellular calcium. This increase in [Ca2+]i carries complex spatial and temporal information important to the physiology of the acinar cell. Research in this laboratory focuses on gaining a better understanding of the mechanisms which underlie these signaling patterns with a primary goal of relating this knowledge to the physiology and pathophysiology of exocrine cells.
Although all Ca2+ mobilizing agonists in pancreatic acinar cells utilize the phosphoinositide-signaling (PI) pathway, stimulation by individual agents results in markedly different temporal and spatial patterns of Ca2+ signaling. One project is designed to understand at the molecular level how the cell effectively "knows" which PI-coupled agonist it is currently exposed to. Given that tremendous molecular diversity is expressed at all levels of this signaling pathway, our working hypothesis is that individual agonists do not couple to the signaling machinery in an identical fashion. This study involves precisely defining by molecular techniques the individual signaling proteins expressed in the acinar cell and then subsequently assessing if individual agonists utilize discrete and different elements of the PI-signaling pathway. We are utilizing fluorescence imaging techniques including high-speed confocal microscopy to monitor [Ca2+]i while manipulating the signaling pathway with neutralizing antibodies and antisense technology.



A further project relates to the organization and regulation of calcium release sites in exocrine cells. These organelles are defined by the expression of receptors for the second messenger Inositol 1,4,5-trisphosphate. In acinar cells the distribution of these receptors is tightly localized to an area associated with the actin cytoskeleton in the apical secretory pole of the cell. This distribution of receptors is the major factor in defining the spatial characteristics of the Ca2+ signal. The nature of the association with the cytoskeleton is being investigated. In addition the regulation of these receptors by phosphorylation and the consequences this may have for Ca2+ signaling are also being studied.

Recent Journal Articles

Showing the 5 most recent journal articles. 104 available »

2013 Apr 19
Alzayady KJ, Chandrasekhar R, Yule DI. "Fragmented inositol 1,4,5-trisphosphate receptors retain tetrameric architecture and form functional Ca2+ release channels." The Journal of biological chemistry.. 2013 Apr 19; 288(16):11122-34. Epub 2013 Mar 11.
2013 Apr 12
Wei-Lapierre L, Gong G, Gerstner BJ, Ducreux S, Yule DI, Pouvreau S, Wang X, Sheu SS, Cheng H, Dirksen RT, Wang W. "Respective contribution of mitochondrial superoxide and pH to mitochondria-targeted circularly permuted yellow fluorescent protein (mt-cpYFP) flash activity." The Journal of biological chemistry.. 2013 Apr 12; 288(15):10567-77. Epub 2013 Mar 01.
2013 Mar 28
Zhang L, Malik S, Pang J, Wang H, Park KM, Yule DI, Blaxall BC, Smrcka AV. "Phospholipase C? hydrolyzes perinuclear phosphatidylinositol 4-phosphate to regulate cardiac hypertrophy." Cell.. 2013 Mar 28; 153(1):216-27.
2013 Jan
Gunter TE, Gerstner B, Gunter KK, Malecki J, Gelein R, Valentine WM, Aschner M, Yule DI. "Manganese transport via the transferrin mechanism." Neurotoxicology.. 2013 Jan; 34:118-27. Epub 2012 Nov 09.
2012 Nov 15
Patterson K, Catalán MA, Melvin JE, Yule DI, Crampin EJ, Sneyd J. "A quantitative analysis of electrolyte exchange in the salivary duct." American journal of physiology. Gastrointestinal and liver physiology.. 2012 Nov 15; 303(10):G1153-63. Epub 2012 Aug 16.

Current Appointments

Professor - Department of Pharmacology and Physiology (SMD) - Primary
Professor - Department of Medicine, Gastroenterology/Hepatology (SMD)
Professor - Center for Oral Biology

Education

PhD | Physiology | UK-Univ of Liverpool1989
BS | Pharmacology | UK-Portsmouth Polytechnic1985

Post-Doctoral Training & Residency

M.R.C. Secretory Control Group, Physiology Department, University of Liverpool. Supervisor: Prof. O.H. Petersen. 0
Department of Physiology, University of Michigan. Supervisor: Prof. J.A. Williams. 1992