CHOW H

Our lab is interested in post-transcriptional regulation of mammalian gene expression, in particular, on how a group of enzymes called endoribonucleases degrade mRNAs and influence the overall biology of gene expression. In addition to understanding the basic biochemical processes of mRNA degradation, we are also interested in using these enzymes and their properties for the treatment of human diseases. We have recently purified and characterized two endoribonucleases that are capable of degrading c-myc mRNA in vitro. We have named these enzymes, PAC-1 (polysome-associated c-myc CRD endonuclease) and PAC-2. Current focuses of our lab include: (1) determining the RNA sequence and structure requirements for cleavage by these enzymes, (2) characterizing the interaction between these enzymes and CRD-BP, an RNA-binding protein, (3) mapping the catalytic domain and studying protein structure/function relationships, and (4) understanding the biological role of these enzymes in cells and animals.

Dept of Advanced Therapeutics, BC Cancer Agency, Vancouver, BC, CANADA; 1997-1998.

McArdle Laboratory for Cancer Research, University of Wisconsin, Madison, USA; 1996-1997.

Affiliate Associate Professor: Department of Biochemistry & Molecular Biology, Faculty of Medicine, UBC; 2004-present.

Visiting Scholar: Department of Molecular, Cellular & Developmental Biology, YALE UNIVERSITY, New Haven, USA; 2003.

Eberding A, Rehaume V, Lee CH. (2004) Detection of mRNA degradation intermediates in tissues using 3’-end poly(A)-tailing polymerase chain reaction method. Anal. Biochem. (in press).

Lee CH. (2004) Drug resistance in cancer therapy: Reversing agents for ABC drug transporters. Curr. Med. Chem. – Anti-Cancer Agents 4: 1-10.

Lee CH, Edwards AM. (2003) Effects of estrogens and other growth-stimulatory

Lee CH, Cragoe EJ Jr, Edwards AM. (2003) Control of hepatocyte DNA synthesis

by intracellular pH and its role in the action of tumor promoters. J. Cell. Physiol.

Lee CH. (2002) Differential regulation of P-glycoprotein genes in primary rat

Lee CH, Edwards AM. (2002) Structural specificity of steroids in stimulating hepatocyte DNAsynthesis and protooncogenes expression in primary culture. J. Steroid Biochem. Mol. Biol. 81: 25-36.

Lee CH. (2001) Induction of P-glycoprotein mRNA transcripts by cycloheximide in

animal tissues: Evidence that class I Pgp is transcriptionally regulated whereas

class II Pgp is post-transcriptionally regulated. Mol. Cell. Biochem. 216: 103-110.

Lee CH, Edwards AM. (2001) Stimulation of DNA synthesis and c-fos messenger

RNA expression in primary rat hepatocytes by estrogens. Carcinogenesis 22:

in primary rat hepatocytes is not mediated by arachidonic acid metabolites. J.

human breast cancer cells are independent of inherent Bcl-2 protein expression.

Lee CH, Leeds P, Ross J. (1998) Purification and characterization of a polysome

associated endoribonuclease that degrades c-myc mRNA in vitro. J. Biol. Chem.

Lee CH, Bradley G, Ling V. (1995) Overexpression of the class II P-glycoprotein

gene in primary rat hepatocyte culture: Evidence for increased mRNA stability.

Zhang J-T, Lee CH, Duthie M, Ling V. (1995) Topological determinants of internal

transmembrane segments in P-glycoprotein sequences. J. Biol. Chem. 270: 1742-

Lee CH, Bradley G, Ling V. (1994) Expression of P-glycoprotein in normal and

malignant rat liver cells. Cold Spring Harbor Symp. Quant. Biol. 59: 607-615.

glycoprotein genes in primary rat hepatocyte culture. J. Cell. Physiol. 157: 392-

Bergstrom K, Lee CH. Evidence for two distinct endoribonucleases capable of cleaving coding region determinant of c-myc mRNA in vitro.

Bergstrom K, Urquhart J, Tafech A, Lee CH. Characterization and purification of PAC-2, a mammalian polysome-associated endoribonuclease that degrades c-myc mRNA in vitro.

Bergstrom K, Urquhart JC, Tafech A, Lee CH. PAC-2, a mammalian polysome-associated endoribonuclease that degrades c-myc mRNA in vitro is a SNAP receptor protein.

Lee CH, Rehaume V, Shandro J. Identification of in vivo P-glycoprotein mRNA decay intermediates in normal liver but not in liver tumours.

Tafech A, Mills F, Bergstrom K, Lee CH. Identification of RNA sequences and structures involved in site-specific cleavage of coding region determinant of c-myc mRNA by PAC-2.