• Research
  • Laboratory of Zebrafish Developmental Genomics: Winata Laboratory, Max Planck/IIMCB Research Group

Laboratory of Zebrafish Developmental Genomics: Winata Laboratory, Max Planck/IIMCB Research Group

Cecilia Lanny Winata, PhD 

Correspondence address:
Laboratory of Zebrafish Developmental Genomics
International Institute of Molecular and Cell Biology
4 Ks. Trojdena Street, 02-109 Warsaw, Poland
Email: This email address is being protected from spambots. You need JavaScript enabled to view it. 
tel: +48 (22) 597 0768; fax: +48 (22) 597 0715

Degrees:
2009 PhD in Biology, Department of Biological Sciences, National University of Singapore
2004 BSc (Hons.) in Biology, Department of Biological Sciences, National University of Singapore

Research experience:
2013 – 2014 Research Associate, Genome institute of Singapore
2013              Research visit, laboratory of Prof. Peter Aleström, Norwegian School of Veterinary Sciences, Oslo, Norway
2009 – 2013 Postdoctoral Fellow with Dr. Sinnakaruppan Mathavan, Genome Institute of Singapore
2004 – 2009 Doctoral research with Profs. Gong Zhiyuan and Vladimir Korzh, Department of Biological Sciences, National University of Singapore

Honors, Prizes and Awards:
2000 – 2004 ASEAN Undergraduate Scholarship
2003             Science Faculty Dean’s List, National University of Singapore
2006             Best poster presentation award, 11th Biological Sciences Graduate Congress

Publications:
Original publications:

  • Winata C.L., Łapiński M., Pryszcz L., Vaz C., Ismail M.H., Hajan H.S., Lee S.G.P., Korzh V., Sampath P., Tanavde V., Mathavan S. (2017) Cytoplasmic polyadenylation mediated translational control of maternal mRNAs direct zebrafish maternal to zygotic transition. Development, Epub ahead of print.
  • Piven O.O., Winata C.L. (2017) The canonical way to make a heart: β-catenin and plakoglobin in heart development and remodeling. Experimental Biology and Medicine, 242(18):1735-1745. 
  • Aksoy I., Utami K.H., Winata C.L., Hillmer A.M., Rouam S.L., Briault S., Davila S., Stanton L.W., Cacheux V. (2017) Personalized genome sequencing coupled with iPSC technology identifies GTDC1 as a gene involved in neurodevelopmental disorders. Human Molecular Genetics, 26(2):367-382.
  • Haihan T., Onichtchouk D., Winata C.L. (2016) DANIO-CODE: Towards an encyclopedia of DNA elements in zebrafish. Zebrafish 13(1):54-60.
  • Winata C.L., Kondrychyn I., Korzh V. (2015) Changing faces of transcriptional regulation by Zic3. Current Genomics 16(2):117-127.
  • Kraus P., Winata C.L., Lufkin T. (2015) BAC transgenic zebrafish for transcriptional promoter and enhancer studies. Methods in Molecular Biology 2015; 1227:245-258.
  • Utami K.H., Winata C.L., Hillmer A.M., Aksoy I., Long H.T., Liany H., Chew E.G., Mathavan S., Tay S.K., Korzh V., Sarda F., Davila S., Cacheux V. (2014) Impaired development of neural-crest cell derived organs and intellectual disability caused by MED13L haploinsufficiency. Human Mutation: 35(11):1311-1320.
  • Aanes H., Winata C.L., Moen L.F., Østrup O., Mathavan S., Collas P., Rognes, T., Aleström P. (2014) Normalization of RNA-sequencing data from samples with varying mRNA levels. PLoS One 9(2): e89158.
  • Winata C.L., Kondrychyn I., Kumar V., Srinivasan K.G., Orlov Y., Ravishankar A., Prabhakar S., Stanton L.W., Korzh V., Mathavan S. (2013) Genome-wide analysis reveals Zic3 interaction with distal regulatory elements to regulate zebrafish developmental genes. PLoS Genetics 9(10):e1003852.
  • Aanes H.*, Winata C.L.*, Lin C.H., Chen J.P., Srinivasan K.G., Lee S.G., Lim A.Y., Hajan H.S., Collas P., Bourque G., Gong Z., Korzh V., Aleström P., Mathavan S. (2011) Zebrafish mRNA sequencing deciphers novelties in transcriptome dynamics during maternal to zygotic transition. Genome Research 21(8): 1328-1338. *equal contribution
  • Lindeman L.C., Andersen I.S., Reiner A.H., Li N., Aanes H., Østrup O., Winata C., Mathavan S., Müller F., Aleström P., Collas P. (2011) Prepatterning of developmental gene expression by modified histones before zygotic genome activation. Developmental Cell 21(6):993-1004.
  • Korzh S., Winata C.L., Zheng W., Yang S., Yin A., Ingham P., Korzh V., Gong Z. (2011) The interaction of epithelial Ihha and mesenchymal Fgf10 in zebrafish esophageal and swimbladder development. Developmental Biology 359(2): 262-76.
  • Yin A., Korzh S., Winata C.L., Korzh V., Gong Z. (2011) Wnt signaling is required for early development of zebrafish swimbladder. PLoS One 6(3): e18431.
  • Lindeman L.C., Winata C.L., Aanes H., Mathavan S., Alestrom P., Collas P. (2010) Chromatin states of developmentally-regulated genes revealed by DNA and histone methylation patterns in zebrafish embryos. International Journal of Developmental Biology 54(5):803-13.
  • Winata C.L., Korzh S., Kondrychyn I., Korzh V., Gong Z. (2010) The role of vasculature and blood circulation in zebrafish swimbladder development. BMC Developmental Biology 10:3.
  • Yin A., Winata C.L., Korzh S., Korzh V., Gong Z. (2010) Expression of components of Wnt and Hedgehog pathways in different tissue layers during lung development in Xenopus laevis. Gene Expression Patterns 10(7-8):338-44.
  • Ung C.Y., Lam S.H., Hlaing M.M., Winata C.L., Korzh S., Mathavan S., Gong Z. (2010) Mercury-induced hepatotoxicity in zebrafish: in vivo mechanistic insights from transcriptome analysis, phenotype anchoring and targeted gene expression validation. BMC Genomics 11:212.
  • Winata C. L., Korzh S., Kondrychyn I., Zheng W., Korzh V., Gong Z. (2009) Development of the zebrafish swimbladder: the requirement of Hedgehog signaling in specification and organization of the three tissue layers. Developmental Biology 331(2):222-36.
  • Korzh S., Pan X., Garcia-Lecea M., Winata C.L., Pan X., Wohland T., Korzh V., Gong Z. (2008) Requirement of vasculogenesis and blood circulation in late stages of liver growth in zebrafish. BMC Developmental Biology. BMC Developmental Biology 8:84.
  • Lam S.H.*, Winata C.L.*, Tong Y., Korzh S., Lim W.S., Korzh V., Spitsbergen J., Mathavan S., Miller L.D., Liu E.T., Gong Z. (2006) Transcriptome kinetics of arsenic-induced adaptive response in zebrafish liver. Physiol. Genomics 27(3):351-61. *equal contribution
  • Lam S.H., Mathavan S., Tong Y., Hu J., Winata C.L., Lee S., Miller L.D., Liu E.T., Gong Z. (2004) Preliminary microarray analyses of gene expression in zebrafish treated with xenobiotic and bioactive compounds. Marine Biotechnology 6: S468-S474.

    Bibliography of lab members:
  • Gross B, Pawlak M, Lefebvre P, Staels B. PPARs in obesity-induced T2DM, dyslipidaemia and NAFLD. 2017. Nat Rev Endocrinol, 13(1):36-49.

The Laboratory of Zebrafish Developmental Genomics, Max Planck/IIMCB Research Group is dedicated to the study of developmental processes by applying genomics methods in combination with experimental embryology, genetics, and biochemistry. The aim is to understand the complex transcriptional regulatory mechanism of embryonic development in vivo. Currently our research focuses on elucidating the downstream regulatory mechanism of heart development by cardiac transcription factors (TFs) and characterization of epigenetic profiles during heart development. A comprehensive understanding of the molecular regulatory networks governing heart development will be a crucial step to a better understanding of the mechanism of congenital heart diseases.

The study of heart development poses a unique challenge due to the importance of the organ for survival. Disruption to factors regulating the early steps of heart formation, cause early embryonic lethality. The zebrafish (Danio rerio) alleviates this problem by allowing access to developing embryos right after fertilization and its ability to survive without a functioning heart up to a comparatively late stage of development. Taking advantage of this model organism, many genes regulating heart development have been identified. However, despite these advances, considerable challenges to understand the mechanism of heart development still exist. Firstly, there is still a lack of knowledge of molecular mechanism and downstream targets of cardiac TFs. Furthermore, the interconnectivity of their mechanisms and functions render it difficult, and possibly of little meaning, to make isolated assessments of individual factors in the characterization of a particular phenotypic outcome. Secondly, the transcription of genes are modulated by cis regulatory elements located in non-coding regions of the genome, which also serve as binding sites for TFs. Thus, mutations in these regulatory elements equally affect developmental outcome as mutations in coding regions. However, there is still a lack of systematic resource for these elements and understanding of their roles in heart development. Thirdly, an additional layer of regulation exists in the form of epigenetics. Cardiac TFs have been shown to interact with chromatin modifying factors, and loss of function of several histone modifying enzymes have been found to affect various aspects of cardiac development.

The high degree of complexity in developmental regulation in vivo necessitates an approach which takes into account both genetic and epigenetic factors. Using a genomics approach and capitalizing on the advantages of zebrafish, we want to uncover genetic and epigenetic factors contributing to the process of heart development and elucidate their regulatory mechanism.

 

1. Transcriptional regulatory network of heart development

The vertebrate heart undergoes three key stages of morphogenesis: specification and migration of cardiac progenitors, formation of the beating linear heart tube, and looping to form a multi-chambered organ. In each of these stages, TFs play a crucial role in initiating transcription of cardiac genes, leading to a cascade of genetic regulation. At the core of this regulation machinery is the interaction between cardiac TFs Nkx2.5, Gata5, Tbx5, and Hand2 which is necessary for the establishment of cardiac identity in cells of the embryonic mesoderm, their subsequent diversification into atrial and ventricular progenitors, and their migration to the midline to form the linear heart tube.

In our previous work, we have used ChIP-seq on zebrafish whole embryos and FACS-sorted cells to study Zic3, a TF implicated in left-right patterning and neural development. We identified novel target genes of Zic3 and uncovered links to several developmental pathways during gastrulation and neural patterning. Building upon the experience and knowledge gained from this study, we want to characterize the downstream regulatory network of cardiac TFs during key phases of heart development.

 

images/labs/winata/CW1.png

Winata et al., 2013 

 

2. Epigenome profile of heart development

Epigenetic marks in the form of modified histones have been commonly used to identify chromatin states, indicating the transcriptional status or activity of particular genetic elements, such as enhancers and promoter. A systematic catalogue of these marks, combined with the information on TF binding sites in the genome, would provide a comprehensive and unbiased view of transcriptional regulatory landscape during heart development in vivo. Together with functional analysis in zebrafish mutants, we aim to identify genome-wide elements associated with heart defects, and to characterize epigenetic contributions to heart development.

 

images/labs/winata/CW2.png

Lab Leader:
Cecilia Lanny Winata, PhD
 
Postdoctoral Fellows:
Katarzyna Nieścierowicz, PhD
Michał Pawlak, PhD
Leszek Pryszcz, Ph
D
Rashid Minhas, PhD
Agata Sułej, PhD

PhD Students:
Maciej Łapiński
Sreedevi Sugunan
Karim Abu Nahia
Maciej Migdał
 
Master Students:
Eugeniusz Tralle
Angelika Brzozowska

Research Assistant:
Alexia Danyłow
Witold Rybski
Natalia Belter

Technican:
Agnieszka Olszewska (part-time)