Thomas Hurley, Ph.D.
Research Interests
The goal of my research is to clarify the
ways in which cells regulate the concentrations of ions in the cytosol and ways
in which changes in cytosolic ion levels
regulate cellular functions. The pancreas
and salivary glands of the rat are used as
model systems to study the cell biology
of the secretory process and to define
the pathways of ion handling in living cells.
Because diseases as diverse as cystic fibrosis, schizophrenia, and muscle disorders
may be due, in part, to derangements in these ion handling pathways, such studies
relate directly to the pathophysiology of disease states in humans. In this work a
variety of techniques are used including cell culture and subcellular fractionation,
ion transport measurements, electrophoresis and autoradiography, as well as direct measurement of cytosolic ion concentrations by spectrofluorometry. These methods
are used to gain insight into the cell biology of secretory organs. For example,
in Figure 1a (below) are shown the changes in cytosolic calcium (Ca2+I)
in pancreatic cells exposed to maximally effective concentrations of two agents (A
and B) which increase Ca2+I. Agent A increases Ca2+I but no further increase
follows addition of agent B. (If B is added first, Ca2+I rises and then agent A
causes no further increase.) In salivary gland cells, however, maximally effective
concentrations of agents A and B each produce an increase in Ca2+I no matter
which is added first (Figure 2a). Since all these changes in Ca2+I depend on entry
of Ca2+ from outside the cells, we interpret these results to mean that, in
pancreatic cells, different plasma membrane receptors (Figure 1b) control a single
Ca2+ influx pathway. In salivary gland cells, on the other hand, different receptors
control separate Ca2+ entry pathways (Figure 2b). The result is that, when both
agents A and B are present, there is an additive increase in Ca2+I in salivary gland
cells but not in pancreatic cells (compare Figures 1c and 2c). Other explanations
of these are also possible. Some of our studies are designed to test alternative
models of cellular ion handling. Other studies are directed toward understanding
changes in the concentration of other ions in the cytosol and the ways in which
those changes may be related to each other. In addition, the role of protein
phosphorylation in controlling ion levels and in regulating the secretory process is
being investigated. Since kinase regulation is the principal mechanism mediating a
wide variety of cellular activities, these studies may give insights into the cell
biology of many differentiated tissue functions.
Professional Background
- Ph.D. in physiology, Duke University
- Joined Department in 1981 with joint appointment in Department of Child
Health
- Elected membership in several professional societies
- Referees manuscripts for a variety of journals
- Serves on NIH review groups
- Research program funded by NIH and the Cystic Fibrosis Association of
Missouri
Selected Publications
- Hurley, T.W., W.E. Dale and M.J. Rovetto. Differing significance of
Na+-Ca2+ exchange in the regulation of cytosolic Ca2+ in rat exocrine gland
acini and cardiac myocytes. Can. J. Physiol. Pharmacol. 70:461-465. 1992.
- Hurley, T.W., M.P. Ryan and R.W. Brinck. Changes of cytosolic Ca2+
interfere with measurements of cytosolic Mg2+ using Mag Fura-2. Am. J.
Physiol. 263:C300- C307, 1992.
- Hurley, T.W., D.D. Shoemaker and M.P. Ryan. Extracellular ATP prevents
the release of stored Ca2+ by autonomic agonists in rat submandibular
gland acini. Am. J. Physiol. 265:C1472-C1478, 1993.
- Hurley, T.W., M.P. Ryan and D.D. Shoemaker. Mobilization of Ca2+ influx, but not of stored Ca2+, by extracellular ATP in rat submandibular gland acini. Arch. Oral Biol. 39:205-212, 1994.
- Hurley, T.W., M.P. Ryan and W.C. Moore. Regulation of changes in cytosolic
Ca2+ and Na+ concentrations in rat submandibular gland acini exposed to
carbachol and ATP. J. Cell. Physiol. 168:229-238, 1996.
Methodology/Techniques
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