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My laboratory studies two overlapping areas with emerging roles in cancer of the immune system. We initially compared gene expression profiles from B cell tumors that arose in immune deficient versus immune competent settings. This approach resulted in the isolation of a large number of differentially expressed genes. We have characterized these isolates and focused on members of the TCL1 gene family, which act like rheostats to control the strength of transduced environmental signals and to regulate gene expression. We have determined that TCL1 promotes cell survival and proliferation by modulating the Akt signaling pathway and probably by interacting with a mRNA degrading enzyme. During normal lymphocyte differentiation, TCL1 is down regulated and shut off; however, in many lymphoid cancers, TCL1 levels remain aberrantly high suggesting a tumorigenic role. We have generated TCL1 transgenic mice that develop lymphoma, establishing this principle. Further characterization indicates that these transgenic mice are the first to accurately model the vast majority of B cell cancers that arise in humans, which has been a major goal in hematology/oncology research for years. Current lab studies include understanding how TCL1 dysregulation contributes to tumor formation through the regulation of Akt and mRNA stability and comparative investigations of additional TCL1 family member proteins. A failure to properly execute developmental gene expression programs can be due to many causes and also leads to cancer. In studies linked to TCL1 gene regulation, we have discovered a novel type of DNA methylation that has a role in altering chromatin structure and gene expression. Methylation of the internal cytosine in CCWGG motifs (W = A or T) causes the silencing of critical genes, such as the p53 tumor suppressor. Current lab studies include broadening studies of epigenetic regulation and its significance in lymphocyte development and neoplasia.
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Chieh Chen,Brett Lomenick,Min Chai,Wilson Huang, Jessie Chu,Laurent Vergnes, Reid O. Johnson,Ajay A. Vashisht,Randall M. Chin,Melissa M. Dix,Gabriel Simon,Xudong Fu,
biorxiv(2022)
Shen Li,Tomohiro Yokota,Ping Wang,Johanna Ten Hoeve,Feiyang Ma,Thuc M Le,Evan R Abt,Yonggang Zhou,Rimao Wu, Maxine Nanthavongdouangsy,Abraham Rodriguez,Yijie Wang,
STAR protocolsno. 3 (2022): 101568-101568
Conference on Lasers and Electro-Opticspp.1-2, (2022)
TRENDS IN CELL BIOLOGYno. 4 (2021): 311-323
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