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Stavroula Mili, Ph.D.

Portait Photo of Stavroula Mili
Laboratory of Cellular and Molecular Biology
Investigator
Center for Cancer Research
National Cancer Institute
Building 37, Room 2042
Bethesda, MD 20892-4256
Phone:  
301-402-0106
Fax:  
301-496-8479
E-Mail:  
voula.mili@nih.gov

Biography

Stavroula (Voula) Mili obtained her BSc degree in Biology from the University of Athens, Greece and her PhD degree in Biomedical Sciences from the Mount Sinai School of Medicine of New York University under Dr. Serafin Pinol-Roma. For her post-doctoral training she joined Dr. Joan Steitz's lab at Yale University and subsequently Dr. Ian Macara's lab at the University of Virginia. She joined the Laboratory of Cellular and Molecular Biology at the NCI in September 2012.

Research

Functions of localized RNAs and their roles in disease
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A large number of mRNAs do not exist diffusely in the cytoplasm, but undergo specific subcellular targeting and local control of their translation. Such localized RNAs are important for various processes such as migration, epithelial cell polarity, mitotic spindle assembly and neuronal function. Defects in RNA localization are implicated in diseases such as mental retardation and cancer metastasis. The lab aims to understand the mechanisms and regulation of RNA localization in mammalian cells, the effect of localized translation on protein function, and the contribution of these processes to disease.

A. The APC-dependent RNA localization pathway
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We have identified an RNA localization pathway that targets numerous mRNAs to cellular protrusions. A central component of this pathway is the tumor suppressor protein Adenomatous Polyposis Coli (APC), which is disrupted in most colorectal cancers. APC associates with RNAs at the plus ends of microtubules in ribonucleoprotein complexes (APC-RNPs). Localization of these RNAs is dependent on APC and is disrupted by cancer APC mutants, suggesting that their deregulation might contribute to tumor progression. We have identified additional components of this pathway and are dissecting their roles and regulation. We aim to understand the functions fulfilled by these localized RNAs, and the contribution of their disruption to cancer progression.

B. Deregulation of localized RNAs by pathological RNA granules
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RNAs can additionally be segregated in the cytoplasm through formation of RNA granules. Assembly of such granules is driven by RNA-binding proteins that contain prion-like domains. These RNA-protein assemblies are normally associated with RNA silencing (stress granules) or degradation (P-bodies). RNA granules have also been linked to pathological conditions. Mutations in the RNA-binding protein Fus result in formation of inclusions in neurodegenerative diseases, such as in ALS (Amyotrophic Lateral Sclerosis) and FTD (Frontotemporal Dementia). We have found that wild type Fus is a component of APC-RNPs at protrusions and regulates their translation. Cytoplasmic granules formed by ALS-associated Fus mutants preferentially recruit APC-RNPs. Interestingly, APC-RNPs are not silenced within Fus granules but are being actively translated. We are interested in understanding the mechanisms directing specificity in formation and functional consequences of RNA granules, the effects of ectopic APC-RNP translation and its potential involvement in neurodegeneration.

We are using a variety of microscopy-based approaches, quantitative image analysis, biochemical assays and high-throughput sequencing. We are also trying to develop new, or adapt existing methodologies to study localized translation and its effects on protein function.

This page was last updated on 4/7/2014.