ZFIN ID: ZDB-LAB-060202-1
Sadler Lab
PI/Director: Sadler Edepli, Kirsten C.
Contact Person: Sadler Edepli, Kirsten C.
Email: Kirsten.Edepli@nyu.edu
URL: http://nyuad.nyu.edu/en/academics/faculty/kirsten-sadler-edepli.html
Address: Sadler Research Laboratory New York University Abu Dhabi Saadiyat Campus P.O. Box 129188 Abu Dhabi, United Arab Emirates
Country: United Arab Emirates
Phone: 971-2-628-4569
Line Designation: nyu

Show all 14 genomic features

Zebrafish are an excellent model for studying embryonic development and we are using the power of zebrafish genetics to define genes required for liver growth as well as to identify new models of liver diseases. Fatty liver disease is emerging as an important liver pathology and is typically associated with obesity and type II diabetes and together these comprise Metabolic Syndrome, which affects nearly 5% of the American population. We have found a zebrafish mutant that develops fatty liver disease in the embryo, and have named it foie gras (fgr). The foie gras gene is well conserved in animals, but has no assigned sequence or motif that suggest its function. The primary focus of the Sadler Edepli lab is to understand the cellular function of foie gras, and to use the fgr mutant embryo as a model for studying fatty liver disease.
The second focus of our lab is to determine the epigenetic basis for liver growth in the embryo and during hepatocarcinogenesis. We focus on the uhrf1 gene which is a major epigenetic regulator, and has been best studied for its role in DNA methylation. We demonstrated that a loss of function mutant in this gene prevents liver outgrowth in embryos and liver regeneration in adults. UHRF1 is overexpressed in many types of cancer and we have shown that UHRF1 is a bone fide oncogene in liver cancer and its widespread overexpression in cancer types across tissues may point to its role in driving the global hypomethylation of the cancer genome. We are now working to dissect the mechanism by which UHRF1 drives oncogenesis and understanding how senescence as a tumor suppressive mechanism gets bypassed in cancers caused by UHRF1 overexpression.

Macchi, Filippo Post-Doc Magnani, Elena Post-Doc Nair, Anjana Ramdas Post-Doc
Zhang, Chi Post-Doc Delaney, Patrice Graduate Student Ranjan, Shashi Administrative Staff

Magnani, E., Macchi, F., Madakashira, B.P., Zhang, C., Alaydaroos, F., Sadler, K.C. (2021) uhrf1 and dnmt1 Loss Induces an Immune Response in Zebrafish Livers Due to Viral Mimicry by Transposable Elements. Frontiers in immunology. 12:627926
Delaney, P., Ramdas Nair, A., Palmer, C., Khan, N., Sadler, K.C. (2020) Arsenic induced redox imbalance triggers the unfolded protein response in the liver of zebrafish. Toxicology and applied pharmacology. 409:115307
Benyettou, F., Das, G., Nair, A.R., Prakasam, T., Shinde, D.B., Sharma, S.K., Whelan, J., Lalatonne, Y., Traboulsi, H., Pasricha, R., Abdullah, O., Jagannathan, R., Lai, Z., Motte, L., Gándara, F., Sadler, K.C., Trabolsi, A. (2020) Covalent Organic Framework Embedded with Magnetic Nanoparticles for MRI and Chemo-Thermotherapy. Journal of the American Chemical Society. 142(44):18782-18794
Hahn, M.E., Sadler, K.C. (2020) Casting a wide net: use of diverse model organisms to advance toxicology. Disease models & mechanisms. 13(4)
Sharma, S.K., Al Hosani, S., Kalmouni, M., Nair, A.R., Palanikumar, L., Pasricha, R., Sadler, K.C., Magzoub, M., Jagannathan, R. (2020) Supercritical CO2 Processing Generates Aqueous Cisplatin Solutions with Enhanced Cancer Specificity. ACS omega. 5:4558-4567
Benyettou, F., Ramdas Nair, A., Dho, Y., Prakasam, T., Pasricha, R., Whelan, J., Traboulsi, H., Mazher, J., Sadler, K., Trabolsi, A. (2020) Aqueous Synthesis of Triphenylphosphine-Modified Gold Nanoparticles for Synergistic In Vitro and In Vivo Photo-thermal Chemotherapy. Chemistry (Weinheim an der Bergstrasse, Germany). 26(23):5270-5279
Benyettou, F., Prakasam, T., Ramdas Nair, A., Witzel, I.I., Alhashimi, M., Skorjanc, T., Olsen, J.C., Sadler, K.C., Trabolsi, A. (2019) Potent and selective in vitro and in vivo antiproliferative effects of metal-organic trefoil knots. Chemical science. 10:5884-5892
Nudelman, G., Frasca, A., Kent, B., Sadler, K.C., Sealfon, S.C., Walsh, M.J., Zaslavsky, E. (2018) High resolution annotation of zebrafish transcriptome using long-read sequencing. Genome research. 28(9):1415-1425
Bambino, K., Zhang, C., Austin, C., Amarasiriwardena, C., Arora, M., Chu, J., Sadler, K.C. (2017) Inorganic arsenic causes fatty liver and interacts with ethanol to cause alcoholic liver disease in zebrafish. Disease models & mechanisms. 11(2)
Madakashira, B., Corbett, L., Zhang, C., Paoli, P., Casement, J.W., Mann, J., Sadler, K.C., Mann, D.A. (2017) Variant Histone H2afv Reprograms DNA Methylation During Early Zebrafish Development. Epigenetics. 12(9):811-824
Chernyavskaya, Y., Mudbhary, R., Tokarz, D., Jacob, V., Gopinath, S., Zhang, C., Sun, X., Wang, S., Magnani, E., Madakashira, B.P., Yoder, J.A., Hoshida, Y., Sadler, K.C. (2017) Loss of DNA methylation in zebrafish embryos activates retrotransposons to trigger antiviral signaling. Development (Cambridge, England). 144(16):2925-2939
DeRossi, C., Shtraizent, N., Nayar, S., Sachidanandam, R., Katz, L.S., Prince, A., Koh, A.P., Vincek, A., Hadas, Y., Hoshida, Y., Scott, D.K., Eliyahu, E., Freeze, H.H., Sadler, K.C., Chu, J. (2017) MPI depletion enhances O-GlcNAcylation of p53 and suppresses the Warburg effect. eLIFE. 6
Wang, S., Miller, S.R., Ober, E.A., Sadler, K.C. (2017) Making It New Again: Insight Into Liver Development, Regeneration, and Disease From Zebrafish Research. Current topics in developmental biology. 124:161-195
Zhang, C., Hoshida, Y., Sadler, K.C. (2016) Comparative Epigenomic Profiling of the DNA Methylome in Mouse and Zebrafish Uncovers High Interspecies Divergence. Frontiers in genetics. 7:110
DeRossi, C., Vacaru, A., Rafiq, R., Cinaroglu, A., Imrie, D., Nayar, S., Baryshnikova, A., Milev, M.P., Stanga, D., Kadakia, D., Gao, N., Chu, J., Freeze, H.H., Lehrman, M.A., Sacher, M., Sadler, K.C. (2016) trappc11 is required for protein glycosylation in zebrafish and humans. Molecular biology of the cell. 27(8):1220-34
Kent, B., Magnani, E., Walsh, M.J., Sadler, K.C. (2016) UHRF1 regulation of Dnmt1 is required for pre-gastrula zebrafish development. Developmental Biology. 412(1):99-113
Chernyavskaya, Y., Kent, B., Sadler, K.C. (2016) Zebrafish Discoveries in Cancer Epigenetics. Advances in experimental medicine and biology. 916:169-97
Jacob, V., Chernyavskaya, Y., Chen, X., Tan, P.S., Kent, B., Hoshida, Y., Sadler, K.C. (2015) DNA hypomethylation induces a DNA replication-associated cell cycle arrest to block hepatic outgrowth in uhrf1 mutant zebrafish embryos. Development (Cambridge, England). 142(3):510-21
Vacaru, A.M., Di Narzo, A.F., Howarth, D.L., Tsedensodnom, O., Imrie, D., Cinaroglu, A., Amin, S., Hao, K., Sadler, K.C. (2014) Molecularly defined unfolded protein response subclasses have distinct correlations with fatty liver disease in zebrafish. Disease models & mechanisms. 7:823-835
Dhandapany, P.S., Razzaque, M.A., Muthusami, U., Kunnoth, S., Edwards, J.J., Mulero-Navarro, S., Riess, I., Pardo, S., Sheng, J., Rani, D.S., Rani, B., Govindaraj, P., Flex, E., Yokota, T., Furutani, M., Nishizawa, T., Nakanishi, T., Robbins, J., Limongelli, G., Hajjar, R.J., Lebeche, D., Bahl, A., Khullar, M., Rathinavel, A., Sadler, K.C., Tartaglia, M., Matsuoka, R., Thangaraj, K., Gelb, B.D. (2014) RAF1 mutations in childhood-onset dilated cardiomyopathy. Nature Genetics. 46(6):635-9
Howarth, D.L., Lindtner, C., Vacaru, A.M., Sachidanandam, R., Tsedensodnom, O., Vasilkova, T., Buettner, C., Sadler, K.C. (2014) Activating transcription factor 6 is necessary and sufficient for alcoholic Fatty liver disease in zebrafish. PLoS Genetics. 10:e1004335
Mudbhary, R., Hoshida, Y., Chernyavskaya, Y., Jacob, V., Villanueva, A., Fiel, M.I., Chen, X., Kojima, K., Thung, S., Bronson, R.T., Lachenmayer, A., Revill, K., Alsinet, C., Sachidanandam, R., Desai, A., SenBanerjee, S., Ukomadu, C., Llovet, J.M., and Sadler, K.C. (2014) UHRF1 overexpression drives DNA hypomethylation and hepatocellular carcinoma. Cancer Cell. 25(2):196-209
Vacaru, A.M., Unlu, G., Spitzner, M., Mione, M., Knapik, E.W., and Sadler, K.C. (2014) In vivo cell biology in zebrafish - providing insights into vertebrate development and disease. Journal of Cell Science. 127(Pt 3):485-495
Tsedensodnom, O., Vacaru, A.M., Howarth, D.L., Yin, C., and Sadler, K.C. (2013) Ethanol metabolism and oxidative stress are required for unfolded protein response activation and steatosis in zebrafish with alcoholic liver disease. Disease models & mechanisms. 6(5):1213-26
Howarth, D.L., Yin, C., Yeh, K., and Sadler, K.C. (2013) Defining hepatic dysfunction parameters in two models of Fatty liver disease in zebrafish larvae. Zebrafish. 10(2):199-210
Sadler, K.C., Rawls, J.F., and Farber, S.A. (2013) Getting the inside tract: new frontiers in zebrafish digestive system biology. Zebrafish. 10(2):129-131
Chu, J., Mir, A., Gao, N., Rosa, S., Monson, C., Sharma, V., Steet, R., Freeze, H.H., Lehrman, M.A., and Sadler, K.C. (2013) A zebrafish model of congenital disorders of glycosylation with phosphomannose isomerase deficiency reveals an early opportunity for corrective mannose supplementation. Disease models & mechanisms. 6(1):95-105
Cline, A., Gao, N., Flanagan-Steet, H., Sharma, V., Rosa, S., Sonon, R., Azadi, P., Sadler, K.C., Freeze, H.H., Lehrman, M.A., and Steet, R. (2012) A Zebrafish Model Of PMM2-CDG Reveals Altered Neurogenesis And A Substrate-Accumulation Mechanism For N-Linked Glycosylation Deficiency. Molecular biology of the cell. 23(21):4175-4187
Chu, J., Loughlin, E.A., Gaur, N.A., Senbanerjee, S., Jacob, V., Monson, C., Kent, B., Oranu, A., Ding, Y., Ukomadu, C., and Sadler, K.C. (2012) UHRF1 phosphorylation by Cyclin A2/CDK2 is required for zebrafish embryogenesis. Molecular biology of the cell. 23(1):59-70
Gerhart, S.V., Eble, D.M., Burger, R.M., Oline, S.N., Vacaru, A., Sadler, K.C., Jefferis, R., and Iovine, M.K. (2012) The Cx43-like Connexin Protein Cx40.8 Is Differentially Localized during Fin Ontogeny and Fin Regeneration. PLoS One. 7(2):e31364
Howarth, D.L., Vacaru, A.M., Tsedensodnom, O., Mormone, E., Nieto, N., Costantini, L.M., Snapp, E.L., and Sadler, K.C. (2012) Alcohol Disrupts Endoplasmic Reticulum Function and Protein Secretion in Hepatocytes. Alcoholism, clinical and experimental research. 36(1):14-23
Cinaroglu, A., Gao, C., Imrie, D., and Sadler, K.C. (2011) Atf6 plays protective and pathologic roles in fatty liver disease due to endoplasmic reticulum stress. Hepatology (Baltimore, Md.). 54(2):495-508
Thakur, P.C., Stuckenholz, C., Rivera, M.R., Davison, J.M., Yao, J.K., Amsterdam, A., Sadler, K.C., and Bahary, N. (2011) Lack of De novo phosphatidylinositol synthesis leads to endoplasmic reticulum stress and hepatic steatosis in cdipt-deficient zebrafish. Hepatology (Baltimore, Md.). 54(2):452-62
Mudbhary, R., and Sadler, K.C. (2011) Epigenetics, development, and cancer: Zebrafish make their MARK. Birth defects research. Part C, Embryo today : reviews. 93(2):194-203
Howarth, D.L., Passeri, M., and Sadler, K.C. (2011) Drinks Like a Fish: Using Zebrafish to Understand Alcoholic Liver Disease. Alcoholism, clinical and experimental research. 35(5):826-829
Imrie, D., and Sadler, K.C. (2010) White adipose tissue development in zebrafish is regulated by both developmental time and fish size. Developmental dynamics : an official publication of the American Association of Anatomists. 239(11):3013-3023
Zhao, X., Monson, C., Gao, C., Gouon-Evans, V., Matsumoto, N., Sadler, K.C., and Friedman, S.L. (2010) Klf6/copeb is required for hepatic outgrowth in zebrafish and for hepatocyte specification in mouse ES cells. Developmental Biology. 344(1):79-93
Monson, C.A., and Sadler, K.C. (2010) Inbreeding Depression and Outbreeding Depression Are Evident in Wild-Type Zebrafish Lines. Zebrafish. 7(2):189-197
Feng, S., Cokus, S.J., Zhang, X., Chen, P.Y., Bostick, M., Goll, M.G., Hetzel, J., Jain, J., Strauss, S.H., Halpern, M.E., Ukomadu, C., Sadler, K.C., Pradhan, S., Pellegrini, M., and Jacobsen, S.E. (2010) Conservation and divergence of methylation patterning in plants and animals. Proceedings of the National Academy of Sciences of the United States of America. 107(19):8689-8694
Chu, J., and Sadler, K.C. (2009) New school in liver development: Lessons from zebrafish. Hepatology (Baltimore, Md.). 50(5):1656-1663
Eichenbaum, J.W., Cinaroglu, A., Eichenbaum, K.D., Sadler, K.C. (2009) A zebrafish retinal graded photochemical stress model. Journal of Pharmacological and Toxicological Methods. 59(3):121-127
Passeri, M.J., Cinaroglu, A., Gao, C., and Sadler, K.C. (2009) Hepatic steatosis in response to acute alcohol exposure in zebrafish requires sterol regulatory element binding protein activation. Hepatology (Baltimore, Md.). 49(2):443-452
Toyoshima, Y., Monson, C., Duan, C., Wu, Y., Gao, C., Yakar, S., Sadler, K.C., and Leroith, D. (2008) The role of insulin receptor signaling in zebrafish embryogenesis. Endocrinology. 149(12):5996-6005
Sadler, K.C., Krahn, K.N., Gaur, N.A., and Ukomadu, C. (2007) Liver growth in the embryo and during liver regeneration in zebrafish requires the cell cycle regulator, uhrf1. Proceedings of the National Academy of Sciences of the United States of America. 104(5):1570-1575
Sadler, K.C., Amsterdam, A., Soroka, C., Boyer, J., and Hopkins, N. (2005) A genetic screen in zebrafish identifies the mutants vps18, nf2 and foie gras as models of liver disease. Development (Cambridge, England). 132(15):3561-3572
Amsterdam, A., Sadler, K.C., Lai, K., Farrington, S., Bronson, R.T., Lees, J.A., and Hopkins, N. (2004) Many ribosomal protein genes are cancer genes in zebrafish. PLoS Biology. 2(5):E139