Davide Ruggero, PhD
Davide Ruggero, PhD
Davide Ruggero, PhD joined UCSF in July 2007 from the Fox Chase Cancer Center in Philadelphia where he was an Assistant Professor in the Department of Human Genetics. Ruggero’s current research seeks to understand the molecular mechanisms by which impairments in mRNA translation, cell growth and overall protein synthesis rates lead to human disease and cancer. The implications of his research results will be applied to design a new generation of cancer therapeutic agents that modulate the cellular proteome at a post-genomic level. Ruggero has received noteworthy funding to support his groundbreaking cancer research. During his graduate and postdoctoral training he was awarded an Enichem Society fellowship and an American-Italian Cancer Foundation fellowship. As a senior post-doctoral fellow Ruggero was one of two candidates, out of more than four hundred, to receive Memorial Sloan-Kettering Cancer Center's Outstanding Research Fellow Award. In 2005 Ruggero received the prestigious V-Scholar Foundation's Award for Cancer Research for his work on deregulations in protein synthesis during lymphomagenesis. The V-Scholar Foundation annually provides grant support to eighteen of the nation's most brilliant young researchers. He is also the recipient of the 2008 Gertrude B. Elion Cancer Research Award from the American Association for Cancer Research that acknowledges the outstanding achievements of one junior faculty in the country toward cancer research. Most recently, Ruggero is a recipient of the 2010 Leukemia & Lymphoma Society Scholar Award. He received full professorship in 2013.
Our research is centered on understanding the molecular mechanisms by which impairments in accurate control of mRNA translation, cell growth, and overall cellular protein synthesis rates lead to cancer. While it is commonly accepted that oncogenic signaling deregulates the transcriptional profile of neoplastic cells, our research has demonstrated a pivotal role for impairments in the translational efficiency of specific existing mRNA species at the post-transcription level towards cancer initiation. Global analysis of the deregulated proteome during cancer formation utilizing novel polysome microarrays pioneered by our lab indicates that control of protein production provides a highly specific, robust, and rabid response to oncogenic stimuli. The mRNAs translationally affected encode proteins involved in cell-cell interaction, cell differentiation, signal transduction, and growth control. These findings strongly suggest that a radical shift in the composition of mRNAs associated with actively translating polysomes may lead to an immediate neoplastic phenotype upon an oncogenic lesion. Our research is uncovering that the direct effect on the proteome may serve as common mechanism elicited by multiple oncogenic signals (i.e. PTEN/AKT/TOR, Ras, Myc) to cause cellular transformation and may overshadow the effect on the transcriptosome.
Our lab has generated the first mouse models for components of the translation machinery, including translation initiation factors and structural components of the ribosome, found mutated in human disease and cancer. Utilizing biochemical, molecular, and genetic approaches within the context of these unique animal models, will continue to address: (1) Which specific steps of protein synthesis control, when deregulated, contribute to cancer initiation and what are the rate limiting steps in protein biosynthesis that are regulated by mitogens and growth factors? (2) What are the target mRNAs, which are affected by aberrant protein translation in neoplastic cells and do they contain specific signatures in their untranslated regions? (3) How is control of translation initiation coupled to cell growth and proliferation and can we apply this knowledge to the discovery of novel therapeutic agents that target the deregulated translational machinery in cancer? The implications of these results will be important in the design of a new generation of compounds that modulate the cellular proteome at the post-genomic level and act as cancer therapeutic agents.
University of California San Francisco
Helen Diller Family Cancer Research Building
Department of Urology, MC 3110 1450 3rd Street
PO Box 589001
San Francisco, CA 94158-9001
(UCSF inter-office mail should be sent to Box 3110)