Peter Vogt, PhD
Professor Emeritus
Department of Molecular and Cellular Biology
Research Focus
Our work is directed at a basic understanding of genetic and epigenetic mechanisms that induce oncogenic transformation of cells. With this information, we conduct screens for small molecules that intervene with the activity of newly identified cancer targets. Our current research focuses on three families of cancer targets: protein and lipid kinases, transcriptional regulators and non-coding, antisense RNA.
Among the kinases, phosphatidylinositol 3-kinase (PI3K) has emerged as an important cancer target, because it is frequently mutated in cancer and because most cancers show increased PI3K activity. We have characterized the cancer-specific mutations in PI3K and continue to explore basic signaling mechanisms that involve this kinase. We are particularly interested in non-redundant, isoform-specific activities of Class IA PI3K. We are also engaged in the characterization of novel specific inhibitors that interfere with oncogenic PI3K.
We have conducted extensive studies on the oncogenic activity of transcriptional regulators, including Myc, Jun, ß-catenin/LEF, and FKHR. Our work on gene transcription now centers on Myc. We have discovered small molecules with the ability to reduce the dimerization of Myc and Max and to interfere with its biological functions. Our current focus is a compound identified from a Krohnke pyridine library in a collaboration with Kim Janda at The Scripps Research Institute. This small molecule binds to Myc, inhibits Myc-induced oncogenic transformation in vitro and in vivo and extinguishes the Myc transcriptional signature.
The vast majority of the transcriptome is non-coding. Non-coding RNAs (lncRNAs) are critical in the epigenetic regulation of gene activity. We have discovered that Myc controls the expression of most lncRNAs. Using a screen based on CRISPR technology, we have now identified numerous lncRNAs that are required for Myc-driven cell proliferation and are in the process of characterizing the functions of these transcripts.
Select Publications
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Hart, J. R.; Garner, A. L.; Yu, J.; Ito, Y.; Sun, M. H.; Ueno, L.; Rhee, J. K.; Baksh, M. M.; Stefan, E.; Hartl, M.; Bister, Klaus; Vogt, Peter K.; Janda, Kim D. Inhibitor of MYC identified in a Krohnke pyridine library. Proceedings of the National Academy of Sciences of the United States of America 2014, 111, 12556-12561.
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