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David I. Yule, Ph.D.

Contact Information

Phone Numbers

Office: (585) 273-2154

Fax: (585) 273-2652

Research Labs

Faculty Appointments



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.



BS | UK-Portsmouth Polytechnic

PhD | UK-Univ of Liverpool

Post-doctoral Training & Residency

1990 - 0
M.R.C. Secretory Control Group, Physiology Department, University of Liverpool. Supervisor: Prof. O.H. Petersen.

1990 - 1992
Department of Physiology, University of Michigan. Supervisor: Prof. J.A. Williams.


Journal Articles

Rosa N, Ivanova H, Wagner LE, Kale J, La Rovere R, Welkenhuyzen K, Louros N, Karamanou S, Shabardina V, Lemmens I, Vandermarliere E, Hamada K, Ando H, Rousseau F, Schymkowitz J, Tavernier J, Mikoshiba K, Economou A, Andrews DW, Parys JB, Yule DI, Bultynck G. "Bcl-xL acts as an inhibitor of IPR channels, thereby antagonizing Ca-driven apoptosis." Cell death and differentiation.. 2021 Nov 8; Epub 2021 Nov 08.

Wahl AM, Yule DI. "An inside job: Annexin 1A-Inositol 1,4,5-trisphosphate receptor interaction conveys endoplasmic reticulum luminal Ca sensitivity." Cell calcium.. 2020 Jul 8; 90:102250. Epub 2020 Jul 08.

Arige V, Yule DI. "Pivotal role of type-1 inositol 1,4,5-trisphosphate receptor for glucagon-induced gluconeogenesis." Cell calcium.. 2020 Jun 10; 90:102243. Epub 2020 Jun 10.

Books & Chapters

Chapter Title: Stimulus-secretion Coupling in Pancreatic Acinar Cells
Book Title: Physiology of the Gastrointestinal Tract, Two Volume Set
Author List: Williams, John A., and Yule, David I.
Edited By: Johnson L, Ghishan F, Kaunitz J, Merchant J, Said H, Wood J
Published By: Elsevier 2012

Chapter Title: Stimulus-Secretion Coupling in the Pancreatic Acinus.
Book Title: Physiology of the Gastrointestinal Tract
Author List: Williams, JA; and Yule, DI
Edited By: Johnson, LR
Published By: Raven Press 2006

Chapter Title: Stimulus-secretion coupling in the pancreatic acinus.
Book Title: Physiology of the Gastrointestinal Tract
Author List: Yule, DI; and Williams, JA
Edited By: Johnson, LR
Published By: Raven Press 1994