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RESEARCH

           Our model system

The kidney is a highly complex organ that performs diverse and specialized functions such as: water and electrolyte balance, excretion of toxic metabolites, and hormone secretion.

These essential functions are highly dependent on a precise trafficking network aimed at maintaining the kidney’s cellular and protein homeostasis.

Hence, it is not surprising that one-third of all monogenic kidney diseases arise from protein trafficking defects. To gain novel insights into the mechanisms contributing to trafficking dysfunction in the kidney, we investigate a collection of genetic mutations associated with protein mistrafficking and accumulation at different sub-cellular localizations

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Our Technique

Being that our work focuses on protein sorting, trafficking, and localization, the ability to visualize proteins in their cellular environment is of paramount importance.

To facilitate the exploration and discovery of new protein trafficking pathways, we use a High Content Screening approach.

High Content Screening combines automated microscopy with multiparametric image analysis to unbiasedly phenotype and elucidate cellular biological mechanisms.

Using this powerful technology, we perform large pharmacologic and genetic screens to comprehensively understand the trafficking network and develop new therapeutics to combat protein traffic jams.

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Specific research projects include:

          How do proteins arrive to their cellular destination?

The cellular proteome is highly rich and diverse. Trafficking processes tightly regulate the proteome and allow it to dynamically respond to internal and external cues.

An essential group of proteins devoted to this function is the TMED protein family that selects and sorts native, fully folded proteins which exit the ER, while retaining misfolded proteins. We are studying how the TMED protein family functions in and aids with transporting proteins to their final cellular destination.

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How do misfolded proteins generate cellular traffic jams?

Many human diseases are associated with the accumulation of misfolded proteins. Our lab studies the mechanisms that facilitate misfolded protein buildup and enable protein quality control.

How does RNA editing affect the trafficking network?

RNA editing modifies the encoded information and differentiates it from the genome. Editing of protein-coding sequences can affect protein stability, localization, and function.

In our lab, we investigate the role of RNA editing and its effect on trafficking components.

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