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My research has focused on several basic and translational aspects of cancer biology. From a basic science perspective, my lab cloned NOL7, a novel gene that induces an anti-angiogenic phenotype and suppresses in vivo tumor growth. NOL7 acts as a master regulator of angiogenesis by modulating the expression of angiogenesis-associated mRNAs via both steady-state downregulation and posttranscriptional upregulation. NOL7 itself is positively regulated by the retinoblastoma (Rb) gene, supporting the paradigm shift that Rb can act as a positive regulator of gene transcription. Our long-term goal is to understand how transcriptional and posttranscriptional regulation of angiogenesis-related mRNAs contributes to the expression of the phenotype and to leverage this knowledge to develop novel therapeutic approaches. Our central hypothesis is that Rb positively regulates NOL7 expression and that loss of NOL7 protein expression results in decreased regulation of NOL7 target mRNA transcripts, the gain of expression of the pro-angiogenic phenotype and the loss of tumor growth inhibition. This research is innovative because it will define the mechanisms by which NOL7 acts as a master regulator of angiogenesis. Further, it provides fundamental insights into the poorly understood area of posttranscriptional regulation of angiogenesis. This research is expected to have a positive impact on human health because it may provide new therapeutic avenues for targeting angiogenesis in both physiologic and pathologic conditions. We have also been pursuing a number of translational research aspects of tumor angiogenesis using head and neck squamous cell carcinoma as a model. For example, we have been testing the hypothesis that inhibitors of angiogenesis are effective chemopreventive agents. The expression of the angiogenic phenotype is both an early and an essential step in the development of cancer, making it an attractive target for cancer prevention. The long-term goal of our work is to develop novel, nontoxic chemopreventive strategies for cancer that are based upon the inhibition of angiogenesis. These investigations have resulted in a number of clinical trials. Finally, we are currently using animal models and tissue derived from the clinical trials to investigate mechanisms of acquired resistance in response prolonged chemopreventive therapy. Such modeling will enable us to test the hypothesis that acquired resistance to inhibitors of angiogenesis can be reversed, thereby prolonging a drug’s chemopreventive activity.
Research Interests
Papers共 240 篇Author StatisticsCo-AuthorSimilar Experts
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NPJ PRECISION ONCOLOGYno. 1 (2024): 114-114
JAMA oncologyno. 7 (2024): 923-931
crossref(2023)
crossref(2023)
Journal of the American Society of Cytopathologyno. 5 (2023): S9-S10
JCO global oncologyno. Supplement_1 (2023): 90-90
Alka Singh, Ashwin Lakshman Koppayi,Ping Wu,Mark W. Lingen,Vasudha Mishra,Alexander Pearson,Ari Rosenberg,Nishant Agrawal,Karthik Suresh,Evgeny Izumchenko
Cancer Researchno. 7_Supplement (2023): 4845-4845
Head and neck pathologyno. 2 (2023): 292-298
Michaela K. Keck,Zhixiang Zuo,Arun Khattri,Thomas P. Stricker, Christopher D. Brown, Matin Imanguli,Damian Rieke,Katharina Endhardt, Petra Fang,Johannes Brägelmann,Rebecca DeBoer, Mohamed El-Dinali,
crossref(2023)
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Author Statistics
#Papers: 242
#Citation: 8250
H-Index: 49
G-Index: 87
Sociability: 7
Diversity: 3
Activity: 43
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