Shuo Lin
Phone: 310-267-4970
Fax: 310-267-4971
Office: 490B BSRB

Research Interests

We use zebrafish to investigate the molecular mechanisms by which diverse and specialized cell types are developed during the vertebrate embryogenesis. Currently, our laboratory is particularly interested in three areas. First, we are working to define the genetic pathways underlying hematopoiesis and vasculargenesis. We are especially interested in identifying those factors that mediate the initial determination of hemangioblast and its subsequent differentiation into blood and vascular lineage-specific progenitor cells. Genetic, transgenic and microarray approaches have been used to identify and characterize these key factors. Secondly, we are studying the genetic basis underlying organ formation. The main focus of this research is to understand the genes and cells that direct pancreatic organogenesis. To this end, a number of zebrafish mutations affecting development of pancreas and endocrine beta cells have been isolated. There is a great need to be able to grow and develop pancreatic beta cells for treating diabetes by cell transplantation. This need challenges us to understand how a precursor cell gives rise to the pancreas and to characterize the gene products that specify cell fates during organogenesis. Finally, we are developing new technologies, such as genetic knockout and high throughput transgenesis, for zebrafish in order to better address fundamental questions raised in our biological studies. We have already developed a streamlined procedure of directly selecting multiple bacterial artificial chromosome (BAC) clones based on public sequence database followed by rapid modification with GFP or RFP. BAC constructs offer greater fidelity in directing desirable expression of transgenes. Application of this technology in the transparent zebrafish embryos with the fluorescent protein reporter genes enables unparalleled visual analysis of gene expression in a living organism. A large-scale analysis of gene regulation using BAC transgenesis and comparative genomics approaches is currently ongoing in the laboratory. We plan to analyze hundreds of highly conserved developmental and disease genes from human, mouse, rat and zebrafish to reveal their common regulatory cis-acting elements and validate them in transgenic zebrafish. Given that developmental programs are well conserved among vertebrate animals, our studies in zebrafish should ultimately lead to a better understanding of the molecular and genetic basis underlying human development.

Selected Publications

Husken U, Stickney HL, Gestri G, Bianco IH, Faro A, Young RM, Roussigne M, Hawkins TA, Beretta CA, Brinkmann I, Paolini A, Jacinto R, Albadri S, Dreosti E, Tsalavouta M, Schwarz Q, Cavodeassi F, Barth AK, Wen L, Zhang B, Blader P, Yaksi E, Poggi L, Zigman M, Lin S, Wilson SW, Carl M., "Tcf7l2 Is Required for Left-Right Asymmetric Differentiation of Habenular Neurons", Curr Biol Epub ahead of print: (2014). [link]

Bibikova E, Youn MY, Danilova N, Ono-Uruga Y, Konto-Ghiorghi Y, Ochoa R, Narla A, Glader B, Lin S, Sakamoto KM., "TNF-mediated inflammation represses GATA1 and activates p38 MAP kinase in RPS19 deficient hematopoietic progenitors", Blood Epub ahead of print: (2014). [link]

Yuan Y, Zhang Y, Yao S, Shi H, Huang X, Li Y, Wei Y, Lin S, "The translation initiation factor Eif3i upregulates vascular endothelial growth factor A, accelerates cell proliferation, and promotes angiogenesis in embryonic development and tumorigenesis", J Biol Chem Epub ahead of print: (2014). [link]

Zhang Y, Ear J, Yang Z, Morimoto K, Zhang B, Lin S., "Defects of protein production in erythroid cells revealed in a zebrafish Diamond-Blackfan anemia model for mutation in RPS19", Cell Death Dis 5: (2014).

Danilova N, Bibikova E, Covey TM, Nathanson D, Dimitrova E, Konto Y, Lindgren A, Glader B, Radu CG, Sakamoto KM, Lin S., "The role of the DNA damage response in zebrafish and cellular models of Diamond Blackfan anemia", Dis Model Mech 7 (7): 895-905 (2014).

Zhang S, Xu M, Huang J, Tang L, Zhang Y, Wu J, Lin S, Wang H., "Heme acts through the Bach1b/Nrf2a-MafK pathway to regulate exocrine peptidase precursor genes in porphyric zebrafish", Dis Model Mech 7 (7): 837-845 (2014).

Qin W, Chen Z, Zhang Y, Yan R, Yan G, Li S, Zhong H, Lin S., "Nom1 mediates pancreas development by regulating ribosome biogenesis in zebrafish", PLoS One 9 (6): (2014).

Lin S, Wang X, Ji Z, Chang CH, Dong Y, Meng H, Liao YP, Wang M, Song TB, Kohan S, Xia T, Zink JI, Lin S, Nel AE., "Aspect ratio plays a role in the hazard potential of CeO2 nanoparticles in mouse lung and zebrafish gastrointestinal tract", ACS Nano 8 (5): 4450-4464 (2014).

Carayannopoulos MO, Xiong F, Jensen P, Rios-Galdamez Y, Huang H, Lin S, Devaskar SU., "GLUT3 gene expression is critical for embryonic growth, brain development and survival", Mol Genet Metab 111 (4): 477-483 (2014).

Liu D, Wang Z, Xiao A, Zhang Y, Li W, Zu Y, Yao S, Lin S, Zhang B., "Efficient gene targeting in zebrafish mediated by a zebrafish-codon-optimized cas9 and evaluation of off-targeting effect", J Genet Genomics 41 (1): 43-46 (2014).

Xiao A, Cheng Z, Kong L, Zhu Z, Lin S, Gao G, Zhang B., "CasOT: a genome-wide Cas9/gRNA off-target searching tool", Bioinformatics 30 (8): 1180-1182 (2014).

Che C, Yang B, Jiang X, Shao T, Yu Z, Tao C, Li S, Lin S., "Syntheses of fused tetracyclic quinolines via Ugi-variant MCR and Pd-catalyzed bis-annulation", J Org Chem 79 (1): 436-440 (2014).

Tong X, Zu Y, Li Z, Li W, Ying L, Yang J, Wang X, He S, Liu D, Zhu Z, Chen J, Lin S, Zhang B., "Kctd10 regulates heart morphogenesis by repressing the transcriptional activity of Tbx5a in zebrafish", Nat Commun 5: (2014).

Xia Z, Tong X, Liang F, Zhang Y, Kuok C, Zhang Y, Liu X, Zhu Z, Lin S, Zhang B., "Eif3ba regulates cranial neural crest development by modulating p53 in zebrafish", Dev Biol 381 (1): 83-96 (2013).

Ren G, Li S, Zhong H, Lin S., "Zebrafish tyrosine hydroxylase 2 gene encodes tryptophan hydroxylase", J Biol Chem 288 (31): 22451-22459 (2013).