Tumor cell response to chemotherapy and gene regulation.
We are investigating how genetic alterations affect cancer cell resistance to chemotherapy, aimed at discovering therapeutic approaches. Drug resistance or poor response to chemotherapy is a crucial reason for treatment failure, which occurs among 60% of patients with metastatic tumors during chemotherapy. Cell response to anticancer agents relies on the functions of certain group of genes involved in cells apoptosis and drug transportation, such as p53 mutation, multidrug resistance-1 (MDR1) and glucosylceramide synthase (GCS). Using state-of-the-art technologies and precision strategy in gene manipulation, we are identifying targets are causes of drug resistance in cancer cells, particularly in cancer stem cells.
Our program is distinguished by characterizing the roles of glycosphingolipids and sphingolipids playing in cancer drug resistance and in regulation of gene expression. We continuously study in:
Project 1: Glycosphingolipids and cancer stem cells. Among glycosphingolipids (GSLs), globotriosylceramide (Gb3/CD77), GD2 and others are highly associated with pluripotency of breast cancer cells. Gb2 can activate cSrc and β-catenin signaling pathways and upregulate stem cell factors.
Project 2: pre-mRNA splicing and expression restoration of p53 mutation. Intriguingly, ceramide can restore p53 tumor suppressor and the anticancer activity in cancer cells carrying p53 mutants (deletion-, missense-mutation). Most likely, ceramide modulates pre-mRNA splicing process and the later determines cells expressing wild-type or mutant proteins by epigenetic mechanism.
Project 3: Epigenetic therapy approaches for cancer drug resistance. With collaborations, we characterize and develop nanoparticles based on natural materials to effectively deliver poor water-soluble agents targeting p53 mutant cells and cancer stem cells.
The goal of our research interests is to discover and develop gene-based therapy that would overcome drug resistance and improve the treatments of cancers, particularly solid tumors in breast and colon.
|Yong-Yu Liu, Ph.D., M.D.
Professor of Pharmacology
Department of Basic Pharmaceutical Sciences
School of Pharmacy
University of Louisiana at Monroe
Monroe, LA 71209-0497