Research Network for Metals in Medicine

 

 

Dr Phillip S. Oates

Position: Senior Lecturer, Physiology

Affiliation: Department of Physiology, The University of Western Australia

Postal Address:
Department of Physiology
The University of Western Australia
35 Stirling Highway CRAWLEY WA 6009
AUSTRALIA

Phone: +61 (08) 9380 1391
Email: poates@cyllene.uwa.edu.au
Webpage: http://www.physiology.uwa.edu.au

Research Profile

Dr Oates has 25 years experience in studies on the digestive system. He started working on the effects of uncooked soya beans on pancreatic growth and its development to neoplastic changes. These studies showed that feeding uncooked soybeans to rats resulted in damage to the exocrine pancreas which rapidly repaired. Along with other studies he confirmed that the pancreas responded to long-term soya feeding by hypertrophy and hyperplasia. It was shown that the hyperplastic response was initially due to proliferation of ductular cells and then acinar cells, suggesting that the stem cell responding to the growth stimulus may be of ductular origin. Further studies revealed that changing the diet from uncooked to cooked soy beans resulted in a rapid return in pancreatic size to normal by apoptosis. This was the first demonstration of this process at a time when apoptosis was not generally accepted as “physiological form of death”. He identified that cells targeted for apoptosis were not selected from the population that underwent hyperplasia but affected old and new cells alike and the loss of cells did not require inflammation because blood flow decreased during apoptosis. Other studies showed that acinar cells of the pancreas have varying ploidy, with the pancreatic acinar cell population being 95% mononucleate at birth but changing to 70% binucleate in the adult. Despite this, it is the mononucleate cell that proliferates during development and therefore appears different to the trophic response produced by raw soya flour in the adult described above. These findings should be viewed from the perspective that feeding uncooked soya beans to rats can results in pancreatic adenomas but the pathophysiology of this process was unexplained. These data indicated that the exocrine pancreas can undergo rapid changes in size and that the mononucleate cell is the cell targeted by the carcinogenic process in the rat. It should also be made clear this work was performed without major research support, but it was obvious that this was needed if more mechanistic explanations to the observations made above were to be found.

In 1990 he retrained to gain experience with cell and molecular biology techniques. He was accepted to carry out a Fellowship at Massachusetts General Hospital. There he assisted in the cloning and characterization of trefoil peptides. These peptides are expressed and secreted by mucous producing cells of the gastrointestinal tract and appear to be involved in wound healing. Other contributions whilst on this Fellowship can viewed below (See below under the heading of characterisation of growth factors in the intestine and pancreas (1991-1993)).

After returning to Perth he studied iron absorption. These studies showed that in homozygous Belgrade rats the uptake transporter involved in iron absorption was defective, and later confirmed that this was due to a G185R mutation in the gene encoding divalent metal transporter 1. Supporting expression on the microvillus membrane of the enterocyte, immunohistochemical studies confirmed that DMT1 was expressed on the microvillus membrane. Other studies revealed that that contrary to a long held view that under certain circumstances significant amounts of iron can be excreted from the body.

Selected Publications

  1. Thomas C, Oates PS. IEC-6 cells are an appropriate model of intestinal iron absorption in rats. J Nutr. 2002;132(4):680-7.
  2. Morgan EH, Oates PS. Mechanisms and regulation of intestinal iron absorption.Blood Cells, Mol., Dis. 2002; 293(3): 384-399.
  3. Thomas C, Oates PS. Copper deficiency increases iron absorption in the rat.Am. J. Physiol. (Gastrointest. Liver Physiol.) 2003; 285: 789-795.
  4. Lee AM, Oates PS, Trinder D. Effects of cell proliferation on the uptake of transferrin-bound iron by hepatoma cells.Hepatology 2003; 38, Pt 4, 967-977.
  5. Thomas C and Oates PS. Ferroportin/Ireg-1/MTP-1/SLC40A1 modulates the uptake of iron at the apical membrane of enterocytes.Gut 2004; 35, 44-49.
  6. Thomas C, Oates PS. Differences in the uptake of iron from Fe(II) ascorbate and from Fe(III) citrate by IEC-6 cells and the involvement of ferroportin/IREG-1/MTP-1.Eur. J. Physiol. (In press).

Facilities

Culture suite, atomic absorption spectrometry, gamma counters, cell lines, radiotracers to track movement of metals.

International Linkages

Professor Nancy Andrews (Children’s Hospital, Harvard USA)