Our laboratory works to understand the mechanism of resistance to anticancer drugs observed in many human cancers. Among other things, we have identified one mechanism of multi-drug resistance (MDR) involving P-glycoprotein (Pgp) which functions as a drug efflux pump of broad specificity. In some cancers the correlation between the presence of Pgp function and non-response to chemotherapy has been established and the use of agents that block Pgp functiton has begun to yield promising results in combination with conventional chemotherapy. Our research in understanding the structure and function of Pgp will provide the fundamental basis for the pharmaceutical industry to design better blockers of Pgp. We and others have also discovered that PgP is a member of a superfamily of related proteins called ABC transporters which may be represented by more than 50 members in the human genome. These transporters are found in all kingdoms of life and appear to be involved in many fundamental biological processes. An inventory of ABC Transporters is currently being generated and we are profiling their expression patterns in different drug-resistant cell lines and some cancers. We are also studying a related liver-specific gene discovered in our lab, the sister of P-glycoprotein (sPgp), and its function in bile formation and cholesterol homeostasis. The mutation of Spgp in humans can cause Progressive Familiar Intrahepatic Cholaestasis -a liver disease, which is often fatal , especially in children. Technologies/expertise in our laboratory include: quantitative RT-PCR, expression profiling, generation of knockout mice, phylogenetic analysis, serial analysis of gene expression (SAGE), Protein biochemistry, Fluorescence labelling, and Transport kinetics.
Dong X, Guan J, English JC, Flint J, Yee J, Evans K, Murray N, Macaulay C, Ng RT, Gout PW, Lam WL, Laskin J, Ling V, Lam S, Wang Y. Patient-derived first generation xenografts of non-small cell lung cancers: promising tools for predicting drug responses for personalized chemotherapy. Clin Cancer Res. 2010 Mar 1;16(5):1442-51.
Wang R, Chen HL, Liu L, Sheps JA, Phillips MJ, Ling V.Compensatory role of P-glycoproteins in knockout mice lacking the bile salt export pump. Hepatology. 2009 Sep;50(3):948-56.
Lo M, Tsao MS, Hedley D, Ling V. Gene expression profiling of adenosine triphosphate-binding cassette transporters in response to K-ras activation and hypoxia in human pancreatic cancer cell cultures. Pancreas. 2009 Jan;38(1):85-93.
Lo M, Ling V, Wang YZ, Gout PW. The xc- cystine/glutamate antiporter: a mediator of pancreatic cancer growth with a role in drug resistance. Br J Cancer. 2008 Aug 5;99(3):464-72.
Lin D, Watahiki A, Bayani J, Zhang F, Liu L, Ling V, Sadar MD, English J, Fazli L, So A, Gout PW, Gleave M, Squire JA, Wang YZ. ASAP1, a gene at 8q24, is associated with prostate cancer metastasis. Cancer Res. 2008 Jun 1;68(11):4352-9.
Ho MM, Hogge DE, Ling V. MDR1 and BCRP1 expression in leukemic progenitors correlates with chemotherapy response in acute myeloid leukemia. Exp Hematol. 2008 Apr;36(4):433-42
Buys TP, Chari R, Lee EH, Zhang M, MacAulay C, Lam S, Lam WL, Ling V. Genetic changes in the evolution of multidrug resistance for cultured human ovarian cancer cells. Genes Chromosomes Cancer. 2007 Dec;46(12):1069-79.
Mak IW, Liu L, Ling V, Kastelic T.The effect of the fungal metabolite radicicol analog A on mRNA degradation. Genomics. 2007 Dec;90(6):723-32. Epub 2007 Oct 23.
Li X, Ling V, Li PC. Same-single-cell analysis for the study of drug efflux modulation of multidrug resistant cells using a microfluidic chip. Anal Chem. 2008 Jun 1;80(11):4095-102.