Translational Medicine
Open Access
ISSN: 2161-1025
ISSN: 2161-1025
Lin Yang
AcceptedAbstracts: Transl Med
Chemotherapy agents are extremely important in the treatment of liquid malignancies, such as multiple myeloma (MM). Unfortunately, chemotherapy resistance in MM therapy is the most significant cause of treatment failure. The ability to predict, treat, or circumvent resistance is extremely likely to improve clinical outcomes. Thus, identification of novel genes that play a crucial role in MM progression and chemosensitivity is necessary to understand this disease better at the molecular level. Moreover, these genes and their products may serve as new therapeutic targets for MM, whose expression could improve patient outcomes or served as a predictor for chemotherapy outcome. Toward this purpose, we have successfully developed a high-throughput siRNA based functional target validation approach and identified a group of potential chemosensitivity genes. Our preliminary studies focusing on one of the candidate gene, ZO1 (zonula occludens 1), suggested that targeting ZO1 led to tumor cell resistant to several chemotherapy agents, including doxorubicin (Dox), cisplatin (Cis), methotrexate (MTX), and bortezomib. Further analysis with 264 bortezomib treated MM patients indicated that expression level of ZO1 correlated with patient response to bortezomib treatment. RPMI 8226 MM cell line, which were developed against bortezomib treatment in our lab, showed loss of ZO1 expression, suggesting a role of ZO1 may play in bortezomib resistance development. More importantly, ZO1 targeting in myeloma cells resulted in cell resistance to bortezomib treatment. Taken together, these studies revealed a novel chemosensitivity gene ZO1, which may form a basis for algorithms to help predict chemosensitivity based on baseline gene expression profiles in the future, and may provide the strategies aimed at enhancing chemosensitivity by increasing expression of target genes of interest.
Yang is currently a Professor at Cyrus Tang Hematology Center, Soochow University and Adjunct Professor at Department of Lymphoma/Myeloma, MD Anderson Cancer Center. In 1998, He obtained his Ph.D degree in Molecular Biology from Sun Yat-Sen University, China. From 2001 to 2003, he was working as a postdoctoral at George Whipple Cancer Laboratory at University of Rochester. From 2003 to 2007, He joined Department of Cancer Biology, MD Anderson Cancer Center to study a novel transcription factor of ZKSCAN3 in tumor progression. From 2008 to 2010, he was promoted as a research instructor at MD Anderson Cancer Center, during which he was working on identification of potential chemosensitivity genes by high throughput functional screening with a shRNA library. So far, he has had more than 50 publications including Cancer Research, J Biol Chem, Oncogene, and EMBO J, etc.