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Jim KoropatnickProfessor, Department of Oncology Ph. D. University of British Columbia |
Clinical Activities
Keywords:
Research Interests
Keywords: Metallothionein and resistance to radiation and chemotherapeutic drug treatment
Description of Research Activities
The development of resistance to radiation or chemotherapy by malignant
cells is a significant cause of failure of cancer therapy. Metallothionein
(MTs) are a class of proteins that have been associated with cellular
resistance to these agents and with homeostasis of essential metals
within cells. We hypothesize that MTs play a critical role in sequestering
or donating essential metals (zinc and copper) to proteins that include
hormone receptors, transcription factors, and enzymes regulating reactive
oxygen molecules. We are investigating this potential role by transfecting
human normal and tumour cells with transcriptionally active rodent and
human metallothionein genes to allow constitutive expression of MT,
or vectors expressing "antisense" RNA to down-regulate MT.
Mice and cultured cells with genetically ablated MT genes (MT knockouts)
are also being used to explore the function of MT. The effect on cell
viability and growth, cellular drug resistance, apoptosis, differentiation
capacity, and susceptibility to chemical and radiation-induced mutation
is being investigated.
(Funded by CIHR)
Thymidylate Synthase (TS) and Cell Growth and Drug Resistance:
The role of thymidylate synthase in cell growth and chemotherapeutic
drug resistance, novel effects on TS gene transcription in response
to antisense nucleic acids, and the usefulness of downregulation of
TS using antisense oligodeoxynucleotides is being explored.
(Funded by Zeneca Pharma Canada, Inc., with Mark Vincent).
