Huili GUO 
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  Huili GUO  
  Lab Location: #5-07

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  Key Publications  

Eichhorn, S.W.*, Guo, H.*, McGeary, S.E., Rodriguez-Mias, R.A., Shin, C., Baek, D., Hsu, S.-H., Ghoshal, K., Villén, J., Bartel, D.P. (2014)
mRNA destabilization is the dominant effect of mammalian microRNAs by the time substantial repression ensues.
Mol Cell
*Equal contributions

Guo, J.U., Agarwal, V., Guo, H., Bartel, D.P. (2014)
Expanded identification and characterization of mammalian circular RNAs.
Genome Biol 15:409.

Guo, H., Ingolia, N.T., Weissman, J.S., Bartel, D.P. (2010)
Mammalian microRNAs predominantly act to decrease target mRNA levels.
466: 835-840.

Okamura, K., Chung, W.-J., Ruby, J.G., Guo, H., Bartel, D.P., Lai, E.C. (2008)
The Drosophila hairpin RNA pathway generates endogenous short interfering RNAs.
Nature 453: 803-806.

McCaw, B.J., Chow, S.Y., Wong, E.S., Tan, K.L., Guo, H., Guy, G.R. (2005)
Identification and characterization of mErk5-T, a novel Erk5/Bmk1 splice variant.
345: 183-190.

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  Huili GUO

Huili Guo graduated from the University of Cambridge in 2005 with a B.A. degree in Natural Sciences. In 2011, she received the Ph.D. degree in Biology from the Massachusetts Institute of Technology. She performed her thesis research in the laboratory of Prof. David Bartel at the Whitehead Institute for Biomedical Research, where she used ribosome profiling and RNA-Seq to study the molecular consequences of microRNA-mediated repression in mammalian systems. This work was published in Nature in 2010. This highly-cited piece of work is recommended by the Faculty of 1000, which identifies the most significant articles in biomedical research publications. Huili is a recipient of National Science Scholarships from the Agency for Science, Technology and Research (A*STAR) in 2002 (BS) and 2006 (PhD). In 2012, she was awarded an IMCB Independent Fellowship to conduct independent research at IMCB. She is an Adjunct Assistant Professor with the Department of Biological Sciences, National University of Singapore. Huili has been an Ambassador for the STEM (Science, Technology, Engineering and Mathematics) programme run by the Singapore Committee for UN Women since 2013. She is also a recipient of the L’Oréal Singapore For Women In Science National Fellowship (2014) and the Young Scientist Award (2016).

  Specialized ribosomes and the control of translation

The ribosome – the cellular machine that translates information in mRNA templates into functional protein – is made up of ribosomal RNAs and about 80 ribosomal proteins. Despite the many components, ribosomes are typically seen as invariant entities. The conventional approach to studying translation has been to treat ribosome recruitment by auxiliary protein factors to mRNA templates as the end-point of translational regulation. However, there has been evidence indicating that the composition of ribosomal proteins in ribosomes can vary and that this in turn leads to distinct phenotypes. This phenomenon has been documented largely in yeast, plants, fruit flies, and zebrafish, but has not been well-studied in mammalian systems, even though many human disorders have been linked with the dysregulation of translation. In particular, there is a class of human genetic disorders known as ribosomopathies, in which mutations occurring in certain genes ultimately lead to impaired ribosome biogenesis and function. The most well-documented ribosomopathy to date is Diamond Blackfan Anaemia – almost half of patients with this disorder have mutations mapping to ribosomal proteins, with as many as 25% mapping to a single ribosomal protein, RPS19, alone.

Ribosome profiling is a recently developed technique used to study translation on a genome-wide level. This high-throughput technique has been demonstrated to provide codon-by-codon resolution of the mRNA locations of translating ribosomes in various organisms, including in mammals. We have previously used ribosome profiling to study microRNA-mediated repression, and are looking to employ this technique in exploring the concept of specialized ribosomes in regulating translation.

Through studying another facet of translational regulatory mechanisms, we hope to gain a deeper understanding of translational control and uncover novel avenues towards therapeutics development.