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.
Feng Z, Nam S, Hamouri F, Aujard I, Ducos B, Vriz S, Volovitch M, Jullien L, Lin S, Weiss S, Bensimon D., "Optical Control of Tumor Induction in the Zebrafish", Sci Rep 7 (9195): 1-12 (2017).
Zhang Y, Qin W, Lu X, Xu J, Huang H, Bai H, Li S, Lin S., "Programmable base editing of zebrafish genome using a modified CRISPR-Cas9 system", Nature communications 8 (118): 1-5 (2017).
Mao Y, Fan T, Gysbers R, Tan Y, Liu F, Lin S, Jiang Y., "A simple and sensitive aptasensor for colorimetric detection of adenosine triphosphate based on unmodified gold nanoparticles", Talanta 168: 279-285 (2017).
Zhang Y, Huang H, Zhao G, Yokoyama T, Vega H, Huang Y, Sood R, Bishop K, Maduro V, Accardi J, Toro C, Boerkoel CF, Lyons K, Gahl WA, Duan X, Malicdan MC, Lin S., "ATP6V1H Deficiency Impairs Bone Development through Activation of MMP9 and MMP13", PLoS genetics 13 (2:e1006481): 1-15 (2017).
Ear J, Lin S, "RNA methylation regulates hematopoietic stem and progenitor cell development", Journal of Genetics and Genomics 1-2 (2017). [link]
Burgess S, Cheng L, Gu F, Huang J, Huang Z, Lin S, Li J, Li W, Qin W, Sun Y, Songyang Z, Wei W, Wu Q, Wang H, Wang X, Xiong JW, Xi J, Yang H, Zhou B, Zhang B., "Questions about NgAgo", Protein & cell 7 (12): 913-915 (2016).
Pei S, Liu L, Zhong Z, Wang H, Lin S, Shang J., "Risk of prenatal depression and stress treatment: alteration on serotonin system of offspring through exposure to Fluoxetine", Scientific reports 6 (33822): 1-11 (2016).
Feng Y, Chen C, Han Y, Chen Z, Lu X, Liang F, Li S, Qin W, Lin S., "Expanding CRISPR/Cas9 Genome Editing Capacity in Zebrafish Using SaCas9", G3 6 (8): 2517-2521 (2016).
Zhao H, Osborne OJ, Lin S, Ji Z, Damoiseux R, Wang Y, Nel AE, Lin S., "Lanthanide Hydroxide Nanoparticles Induce Angiogenesis via ROS-Sensitive Signaling", Small 12 (32): 4404-4411 (2016).
Zhao H, Huang H, Lin S., "Chemical approaches to angiogenesis in development and regeneration", Methods in cell biology 134: 369-376 (2016).
Zhang Y, Huang H, Zhang B, Lin S., "TALEN- and CRISPR-enhanced DNA homologous recombination for gene editing in zebrafish", Methods in cell biology 135: 107-120 (2016).
Pei W, Tanaka K, Huang SC, Xu L, Liu B, Sinclair J, Idol J, Varshney GK, Huang H, Lin S, Nussenblatt RB, Mori R, Burgess SM., "Extracellular HSP60 triggers tissue regeneration and wound healing by regulating inflammation and cell proliferation", NPJ Regen Med 1 (16013): 1-30 (2016).
Ear J, Hsueh J, Nguyen M, Zhang Q, Sung V, Chopra R, Sakamoto KM, Lin S., "A Zebrafish Model of 5q-Syndrome Using CRISPR/Cas9 Targeting RPS14 Reveals a p53-Independent and p53-Dependent Mechanism of Erythroid Failure", Journal of genetics and genomics 43 (5): 307-318 (2016).
Wu W, Hai Y, Chen L, Liu RJ, Han YX, Li WH, Li S, Lin S, Wu XR., "Deguelin-induced blockade of PI3K/protein kinase B/MAP kinase signaling in zebrafish and breast cancer cell lines is mediated by down-regulation of fibroblast growth factor receptor 4 activity", Pharmacology research & perspectives 4 (2:e00212): 1-15 (2016).
Zhao C, Zhang W, Zhao Y, Yang Y, Luo H, Ji G, Dong E, Deng H, Lin S, Wei Y, Yang H., "Endothelial Cords Promote Tumor Initial Growth prior to Vascular Function through a Paracrine Mechanism", Scientific reports 6 (19404): 1-13 (2016).