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Full-Text Articles in Molecular Biology

P53 Drives A Transcriptional Program That Elicits A Non-Cell-Autonomous Response And Alters Cell State In Vivo, Sydney Moyer Dec 2020

P53 Drives A Transcriptional Program That Elicits A Non-Cell-Autonomous Response And Alters Cell State In Vivo, Sydney Moyer

Dissertations & Theses (Open Access)

Cell stress and DNA damage activate the tumor suppressor p53, triggering transcriptional activation of a myriad of target genes. The molecular, morphological, and physiological consequences of this activation remain poorly understood in vivo. We activated a p53 transcriptional program in mice by deletion of Mdm2, a gene which encodes the major p53 inhibitor. By overlaying tissue-specific RNA-sequencing data from pancreas, small intestine, ovary, kidney, and heart with existing p53 ChIP-sequencing, we identified a large repertoire of tissue-specific p53 genes and a common p53 transcriptional signature of seven genes which included Mdm2 but not p21. Global p53 activation …


Effects Of Penfluridol On Integrin-Fak Signaling And Tumor Cell Killing In Combination With Oncolytic Hsv In Glioblastoma, Mitra Nair May 2020

Effects Of Penfluridol On Integrin-Fak Signaling And Tumor Cell Killing In Combination With Oncolytic Hsv In Glioblastoma, Mitra Nair

Dissertations & Theses (Open Access)

Integrins are known to play an important role in activating multiple intracellular pathways, one of which is focal adhesion kinase (FAK). Phosphorylation of FAK can lead to the activation of various downstream signaling pathways that can increase tumor cell growth and proliferation, making it an ideal target for cancer therapeutics. Due to the fact that many FAK inhibitors are limited in their penetration of the blood brain barrier, we investigated the use of Penfluridol, an antipsychotic drug known to attenuate integrin expression at a transcriptional level, in combination with oncolytic herpes simplex I virus (oHSV) in a glioblastoma model. We …