What we study

RNA metabolism includes the transcription, splicing, modification, transportation, translation, and degradation of RNA molecules. The Ruan lab’s research aims to understand how genetic/environmental factors affect RNA metabolism in humans and why dysregulation of this process causes diseases. We are passionate about revealing non-coding RNA-mediated human-specific regulatory mechanisms controlling gene expression in health and diseases.

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Why it is important

Defects of RNA metabolism cause many human diseases, like diabetes, Parkinson's disease, and premature aging. As almost all key elements involved in RNA metabolism, including promoters, splicing signals, untranslated regions of mRNA are poorly conserved among different species, our knowledge gained in model animals may not easily be applied to humans. New strategies to study human RNA metabolism at the organism level are crucial to understanding the development of diseases.

Why we are the team

Our previous research (PMID: 33048844; PMID: 31896749) has established the humanized liver mouse model as a powerful tool to study human-specific regulation of gene expression. We continue optimizing humanized mouse models to study RNA metabolism in different human organs. We integrate human genetic data to define novel regulators of RNA metabolism, especially long non-coding RNAs (lncRNAs). In combination with CRISPR mediated genome editing, gene activation/inhibition, and RNA biology tools defining in vivo RNA-protein interactions, we are the team to reveal the mystery of human RNAs.

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Current projects

 

We recently identified hLMR1, a human-specific lncRNA, that transcriptionally controls the hepatic lipid biosynthesis. GWAS-eQTL integration supports that the expression of hLMR1 is strongly correlated with the blood lipid levels in human populations. In this project, we aim to address:

  1. How genetic variants affect the expression of hLMR1

  2. How nutrients and hormones affect the expression of hLMR1

  3. How hLMR1 coordinates with SREBP2 to control the transcription of genes in the lipid biosynthesis pathway

Instead of a constitutive process, RNA degradation, especially the 5′ degradation pathway is now recognized as a dynamic cellular event that is regulated by stresses and nutrients. In this project, we aim to determine:

  1. How overnutrition affect the RNA degradation in the liver

  2. The role of RNA 5′-end processing enzymes (XRN and DCP genes) in the development of fatty liver diseases

  3. The strategy to treat fatty liver diseases by inducing RNA degradation-transcription futile cycle

Global changes of pre-mRNA splicing are a crucial factor that contributes to aging-related phenotypes. Nuclear lncRNAs have emerged as an essential component regulating pre-mRNA splicing. In this project, we will test the core hypothesis that aberrantly expressed, nuclear-enriched lncRNAs disrupt pre-mRNA splicing to accelerate aging by blocking the activity of splicing factors.

 

We are hiring team members

We are not big names. We are just brave enough to ask tough questions, flexible enough to enjoy St. Pete Beach, and happy enough to do solid research.

If you want to join us as a post-doc or lab technician, please send your message in whatever way you like:

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