Northwestern Events Calendar

Sep
26
2019

BMG Seminar: Decoding the cancer genome one codon at a time and its therapeutic implications -Davide Ruggero, PhD

CANCELLED

When: Thursday, September 26, 2019
10:00 AM - 11:00 AM CT

Where: Simpson Querrey Biomedical Research Center, SQBRC Auditorium, 303 E. Superior Street, Chicago, IL 60611 map it

Audience: Faculty/Staff - Student - Post Docs/Docs - Graduate Students

Contact: Vanessa Hughes   (312) 503-5229

Group: Biochemistry & Molecular Genetics Seminar Series

Category: Lectures & Meetings

Description:

Our research is centered on understanding translational control of gene expression in both normal health and disease, with a particular focus on cancer biology. Our research combines mouse genetics with genome-wide translational profiling, in-depth molecular biology, and pharmacology to systematically define the points of regulation, in cis and trans, by which the genome is selectively decoded into proteins in a cell- and tissue-specific manner. We have uncovered that a common denominator of multiple oncogenic pathways is their ability to directly control the core translation machinery of a cell, resulting in the rapid remodeling of mRNA translation programs that promote distinct hallmarks of cancer development, such as cell growth, metabolism, and increased motility. Our most recent findings delineate the in vivo requirements for a distinct threshold of the major cap-binding protein, eIF4E, in normal organismal development compared to those required for translating the cancer genome. We show that increased eIF4E activity is essential for cancer cell survival as distinct subsets of mRNAs that regulate the cancer cell oxidative response are marked by the presence of a novel, eIF4E-dependent cis-acting motif present in their 5’UTRs. I will also discuss a new link between translational nutrient availability to maintain metabolic fitness and health span in vivo. In particular, we are defining the role of translation regulation for the first time in the poorly understood molecular program underlying increased risk of cancer development associated with obesity. I will also discuss the generation of the first comprehensive systems-level analysis of the ‘cancer translatome’ during cancer development in vivo that highlights a dichotomy in transcriptional vs. translational control of gene expression guiding key, select steps in cancer development and evolution. The immediate impact of our research has been the design of a new generation of compounds to target the aberrant translation machinery in cancer cells, which are currently in clinical trials, and may reflect a new frontier in cancer therapy.

Davide Ruggero, PhD
Professor, Department of Urology
Helen Diller Family Chair in Basic Cancer Research
University of California San Francisco



 

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