Li-En Jao, Ph.D.

 Li-En   Jao, Ph.D.

Position

  • Assistant Professor
  • Cell Biology and Human Anatomy

Contact

Centrosome Biology in Neurogenesis, Zebrafish Disease Models

Research Summary

The roles of centrosomes and cilia in development and disease

My laboratory is interested in understanding how the centrosome and its related organelles (e.g., the cilium) regulate cell function and influence development. Dysfunction of centrosomes and cilia has been linked to a plethora of human diseases, including cancer, dwarfism, microcephaly (disorders with small head size), and various ciliopathies (diseases caused by dysfunction of cilia). However, little is known about how the perturbation of these centrosome-related functions leads to a wide spectrum of disorders.

Using a combination of approaches encompassing proteomics, cell biology, zebrafish genetics, and in vivo live microscopy, we aim to dissect the roles of centrosomes and cilia in various biological contexts, including neurogenesis and cell signaling. Specifically, we are elucidating how the microcephalic phenotype develops upon centrosomal dysfunction using the zebrafish forebrain as the model system. We also investigate how the orderly organization of the pericentriolar material (PCM) is dynamically regulated and influences centrosomal function. Our research goal is to bridge the knowledge gap between centrosomal dysfunction and manifestation of disease phenotypes.

Some of the questions we are pursuing include:

1. How is centrosomal dysfunction translated into developmental defects such as microcephaly during early vertebrate neurogenesis?

2. How is the PCM dynamically remodeled at different cell cycle stages?

3. What is the role of the PCM in centriole maturation and ciliogenesis?

4. How is the coordinated movement of motile cilia achieved?

Selected Publication

2015 Kaneb HM, Folkmann AW, Belzil VV, Jao LE, Leblond CS, Girard SL, Daoud H, Noreau A, Rochefort D, Hince P, Szuto A, Vidal S, André-Guimont C, Camu W, Bouchard JP, Dupré J, Meininger V, Rouleau GA, Wente SR, and Dion PA. Deleterious mutations in the essential mRNA metabolism factor, hGle1, in amyotrophic lateral sclerosis. Human Molecular Genetics 24: 1363-1373.

2013  Jao LE, Wente SR, Chen W. Efficient multiplex biallelic zebrafish genome editing using a CRISPR nuclease system. Proc. Natl. Acad. Sci. USA. 110:13904-13909.

2013  Varshney GK, Lu J, Gildea DE, Huang H, Pei W, Yang Z, Huang SC, Schoenfeld D, Pho N, Diaz-Cano DC, Hirase T, Moshbrook-Davis D, Zhang S, Jao LE, Zhang B, Wolfsberg TG, Pellegrini M, Burgess SM, and Lin S. A large-scale zebrafish gene knockout resource for the genome-wide study of gene function. Genome Research 23: 727-735.

2012  Jao LE, Appel B, and Wente SR. A zebrafish model of lethal congenital contracture syndrome 1 reveals Gle1 function in spinal neural precursor survival and motor axon arborization. Development 139: 1316-1326.


2007  Wang D*, Jao LE*, Zheng N, Dolan K, Ivey J, Zonies S, Wu X, Wu K, Yang H, Meng Q, Zhu Z, Zhang B, Lin S, and Burgess SM (2007). Efficient genome-wide mutagenesis of zebrafish genes by retroviral insertions. Proc. Natl. Acad. Sci. USA. 104: 12428-12433.

*Equal contributions

Affiliation

Biochemistry, Molecular, Cellular and Developmental Biology Graduate Group

Integrative Genetics and Genomics Graduate Group

Neuroscience Graduate Group