David X. Liu, Ph.D. in Molecular Genetics
Associate Professor, Department of Neural and Behavioral Sciences, College of Medicine
Northeastern State University Gregg Wadley College of Science & Health Professions, USA
My laboratory studies the molecular and cellular mechanisms that control cell proliferation and survival. Our goal is to identify molecules and signaling pathways that are deregulated in major human diseases as in cancer and to use this knowledge for therapeutic intervention. Recent work from my laboratory and several other laboratories have shown that the activating transcription factor 5 (ATF5) is required for cell survival in cancer cells but is dispensable in non-cancer cells. We also found that ATF5 deficiency significantly reduced tumor burden in PyMT mice. Mechanistically, we demonstrated that ATF5 activates the transcription of Bcl-2 and Egr-1, promoting cell survival and proliferation, and acts as an essential structural component in the centrosome, regulating genomic stability in a cell-cycle-dependent manner. Our studies further indicated that ATF5 is enriched at the midbody and controls cytokinesis. In addition, ATF5 is interdependently activated with NFkB and c-Src in transformed cells, which in turn activates the PI3K/mTOR signaling pathway. Moreover, our data indicated that ATF5 plays an essential role in the transformation-dependent activation of 5’-terminal polypyrimidine track (5’-TOP) genes, whose expression is tightly associated with cell proliferation and survival and is exclusively regulated at translational level. Our work has been published in peer-reviewed journals including Cell, Neuron, Genes&Dev., Molecular Cell, Nature Communications, Oncogene, Cancer Research, among others, and is currently supported by a grant from NCI.