Room 6614, Pharmaceutical Sciences Building
2405 Wesbrook Mall
Dr. Wong is an Associate Professor in the Faculty of Pharmaceutical Sciences at the University of British Columbia (UBC). Judy Wong obtained a PhD in Pharmacology from the University of Toronto. She was a post-doctoral fellow in the Department of Molecular and Cell Biology at the University of California, Berkeley.
Research Areas of Interest
Dr. Wong investigates mechanisms responsible for the gross structural maintenance of the genome, the role of telomeres and telomerase in preventing chromosome erosion, and the cellular pathways that respond to DNA damage. Most cancers and premature aging syndromes share an observable loss of genome integrity. Her long-term goal is to discover genetic and pharmacological means to control cellular changes that affect stable genome maintenance.
- Non-canonical activities of telomerase reverse transcriptase in cancer
New evidence suggests that high telomerase activity promotes survival of cancer cells in stressful conditions, such as treatment with chemotherapeutic agents. These growth advantages provided by telomerase expression are mediated through cellular functions not related to telomere repair. We intend to deduce the mechanisms of these telomerase activities in detail, and develop pharmacological strategies to inhibit them.
- Inheritance and disease mechanisms of X-linked dyskeratosis congenita
X-linked dyskeratosis congenita (X-DC) is a bone-marrow-failure syndrome, caused by mutations in the DKC-1 gene, which encodes for the housekeeping enzyme dyskerin. Dyskerin is a pseudouridinylase enzyme that modifies RNAs. This is important for the structural and functional integrity of ribosomes, which are responsible for protein translation. Dyskerin is also a component of the telomerase reverse transcriptase, which repairs the end of chromosomes. More than forty dyskerin mutations are currently known to associate with X-DC. In collaboration with the US National Insitutes of Health, we have created model cell lines from X-DC patients, to study the inheritance and disease mechanism of X-DC, as a paradigm for pre-mature aging.
- Therapeutic development of DNA-binding chemicals
Cancers have become resistant to treatment over time. New therapeutic strategies are needed to counter such resistance when it develops. We propose that a novel class of DNA-binding chemicals be developed for clinical application. Using a functional genomics approach, we intend to characterize the cellular effects of treatments with these agents.
- Genetic variations in telomere maintenance
Epidemiological data has recently linked common genetic changes in the telomerase holoenzyme to high incidences of various cancers. Our hyptohesis is that telomerase function is altered by these genetic changes. We propose to study this in human cells.
Trudeau MA and Wong, JM. Genetic Variations in Telomere Maintenance, with Implications on Tissue Renewal Capacity and Chronic Disease Pathologies. Curr. Pharmacogenomic Person Med. 8(1):7-24. (2010)
Tamakawa RA, Fleisig HB and Wong JMY. Telomerase inhibition potentiates the effects of genotoxic agents in breast and colorectal cancer cells in a cell cycle specific manner. Cancer Res 70:8684-94. (2010)
Fleisig HB and Wong JMY. Telomerase promotes efficient cell cycle kinetics and confers growth advantage to telomerase-negative transformed human cells. Oncogene 31(8):954-65. (2012)
Zeng XL, Thumati NR, Fleisig HB, Hukezalie KR, Savage SA, Giri N, Alter BP and Wong JMY. The accumulation and not the specific activity of telomerase ribonucleoprotein determines telomere maintenance deficiency in X-linked dyskeratosis congenita. Hum Mol Genet 21(4):721-9. (2012)
Fleisig H, Wong J. Measuring cell cycle progression kinetics with metabolic labelling and flow cytometry. J Vis Exp 63.pil:4045. (2012)
Hukezalie KR, Thumati NR, Cote H and Wong JMY. In vitro and ex vivo effects of anti-HIV nucleoside and non-nucleoside reverse transcriptase inhibitors on cellular telomerase activities. PLoS One. 7(11): e47505. doi:10.1371/journal.pone.0047505. (2012).
Hukezalie KR and Wong JM. Structure-function relationship and biogenesis regulation of the human telomerase holoenzyme. FEBS J. 280(14):3194-204 (2013).
Thumati NR, Zeng XL, Jang C, Au H, Jan E and Wong JMY. Severity of X-linked dyskeratosis congenita (DKCX) cellular defects is not directly related to dyskerin (DKC1) activity in ribosomal RNA biogenesis or mRNA translation. Hum Mutat. 34(12):1698-707 (2013).