Robert W. Freel Ph.D.
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Dept.
of Pathology, Immunology and Laboratory Medicine Office Location and
Express Mail address: Office:
(352) 392-8472 |
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Primary Area of Research: Our overall research interests concern the mechanisms and regulation of solute transport across epithelial membranes in health and disease. At the present time, our efforts are directed at understanding the cellular mechanisms mediating the secretion of oxalate and other divalent anions by renal and intestinal epithelia. The oxalate anion is of considerable importance because it forms insoluble complexes with calcium in the lumen of the renal tubule leading, in some conditions, to the formation of renal stones. Our recent studies suggest that the intestinal secretion of oxalate occurs via cAMP-stimulated transport pathways that are similar (if not identical) to those mediating monovalent anion secretion and that these pathways are up-regulated when renal function is impaired; providing an extrarenal pathway for the excretion of the oxalate anion. Currently, we are employing a variety of approaches to establish the nature of apical membrane oxalate conductance (patch clamp, membrane vesicles, Ussing chambers); the impact of variable intracellular oxalate on cell calcium signaling in oxalate transporting epithelia (spectrofluorometry); and the regulatory pathways involved in enhanced enteric oxalate secretion (real time-PCR and other molecular biological techniques). Our group also maintains
an active interest in the regulation of potassium ion transport by the
mammalian large intestine. Our studies in this area have provided two
novel regulatory pathways for potassium ion secretion in the large
intestine: an angiotensin II receptor mediated up-regulation of
potassium ion secretion and muscarinic down-regulation of potassium ion
secretion. Selected Recent
Publications Hatch M., Gjymishka A., Salido E. C., Allison M.J., and
Freel R. W. 2011. Enteric oxalate elimination is induced
and oxalate is normalized in a mouse model of primary hyperoxaluria
following intestinal colonization with Oxalobacter. Am. J. Physiol. Gastrointest. Liver
Physiol. 300(3): G461- G469. Freel, R.W., Morozumi, M., and Hatch, M. 2009.
Parsing apical oxalate exchange in Caco-2BBe1 monolayers: siRNA
knockdown of SLC26A6 reveals the role and properties of PAT-1. Am. J. Physiol. Gastrointest. Liver Physiol. 297:
G918-G929. Hatch, M. and
Freel, R. W. 2008. Increased colonic sodium absorption in
rats with chronic renal failure is partially mediated by AT1 receptor
agonism. Am. J. Physiol.
(Gastrointest. Liver Physiol.)
295(2):G348-356. Freel, R. W. and Hatch, M. 2008.
Enteric oxalate secretion is not directly mediated by the human CFTR
chloride channel. Urol. Res. 36(3-4):127-131. Hatch, M. and
Freel, R. W. 2008. The roles and mechanisms of intestinal oxalate
transport in oxalate homeostasis.
Semin Nephrol. 2008 Mar;28(2):143-151. Hatch M., Cornelius J., Allison M., Sidhu H., Peck A.,
and Freel R. W. 2006. Oxalobacter sp. reduces urinary oxalate
excretion by promoting enteric oxalate secretion. Kidney Int. : 69:
691-708. Freel, R. W., Hatch M., Green M., and Soleimani M. 2006. Ileal Oxalate Absorption and Urinary Oxalate Excretion Are Enhanced In Slc26a6-Null Mice. Am. J. Physiol. (Gastrointest. Liver Physiol.) 290: G719-G728. |
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Related Links:
Curriculum Vitae (click to download MS-Word
document)
Publications
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