RESEARCH PROJECTS

 

1. Regulation of Lung Cancer and Metastasis

Our lab has been examining the molecular mechanisms by which tobacco smoke components, especially nicotine, promotes self-renewal, epithelial-mesenchymal transition, and metastasis. We are focusing on the role of the Hippo pathway, TBK1 kinase and b-arrestin in the context of nicotinic acetylcholine receptor signaling.

2. Modulation of YAP1 function in lung cancer 

Our lab has recently discovered a novel regulation of YAP1 by arginine methylation. Mechanistic studies to elucidate the mechanisms and players involved as well as the translational potential of these studies in overcoming drug resistance are going on.  This is a major research effort in the lab.  IN a similar vein, studies are also in progress to understand the differential regulation of YAP1 levels in normoxia and hypoxia.

3. Development of novel drugs that target YAP1 interactions 

Our lab had discovered a novel interaction of YAP1 with the transcription factor, Oct4, which facilitated the induction of Sox2.  A drug discovery project, conducted in collaboration with the Nick Lawrence lab, is in fairly advanced stage.  We now have novel compounds that selectively disrupt the binding of YAP1 to Oct4; they suppress Sox2 expression, self-renewal of stem-like cells, cell proliferation, growth of lung cancer organoids and growth of lung cancer xenografts in mice.

4. TBK1-mediated signaling events

Our lab had reported a novel role for TBK1 in mitosis.  We are examining the signaling events that promote the unexpected proliferative signaling events that occur when TBK1 is inhibited or depleted.  Role of TBK1 in modulating T cell-mediated anti-tumor immunity is also being studied.

5. Role of transcriptional CDKs in glioblastoma and lung cancer 

Novel roles for CDK7 and CDK9 in regulating the growth and stemness of GBM and lung cancer are being studied.  Especially, inhibitors are CDK7/9 appear to be highly effective in suppressing the self-renewal of glioma stem cells and growth of GBM tumors in mice.