Kirsten Sadler Edepli, PhD
- ADJUNCT ASSOCIATE PROFESSOR | Medicine, Liver Diseases
The Sadler laboratory belongs to:
The Department of Developmental and Regenerative Biology
The Department of Medicine/Division of Liver Diseases
Training areas in Development and Stem Cell Biology, Cancer Biology and Genetics and Genomics
The Mount Sinai Zebrafish Facility is managed by Dr. Sadler.
Cancer, Cell Biology, Developmental Biology, Diabetes, Embryology, Genetics, Liver, Morphogenesis, Obesity, Organogenesis, Oxidative Stress, Regeneration, Tumorigenesis
BA, Mount Holyoke College
MMSc, Harvard Medical School
PhD, Harvard University
fellowship, Massachusetts Institute of Technology
Harold and Golden Lamport Award
Mount Sinai School of Medicine
Basil O'Connor Starter Scholar Award
March of Dimes
Research Scholar Award
American Gastroenterological Association
Dr. Sadler-Edepli is the Director of the Zebrafish Models of Liver Disease Laboratory and the Model Co-Core Director of the Mount Sinai Alcoholic Liver Disease Research Center.
Specific Clinical/Research Interest: Using zebrafish to understand liver development, regeneration and disease.
Students: Brandon Kent (co-mentored with Dr. Martin Walsh)
Postdoctoral Fellows: Yelena Chernyavskay, Chi Zhang
Research Personnel: Ruhina Rafiq, Patrick Bradley (Zebrafish Facility manager)
Faculty: Jaime Chu, M.D.
Current Research Focus
Using zebrafish to understand liver development, regeneration and disease
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 percent of the American population. We have found a zebrafish mutant that develops fatty liver disease in the embryo, and have named it foie gras (foiegr). The foie gras gene is well conserved in animals, and has recently been shown to be a component of the TRAPP complex (trappc11) which functions to tether vesicles in the secretory pathway to their destination compartment. We found that there is significant activation of the unfolded protein response (UPR) in foigr/trappc11 mutants and that in zebrafish, as in mammals, robust UPR induction is sufficient to cause fatty liver disease. Research in the Sadler lab focuses on understanding the relationship between UPR activation and fatty liver disease, understanding the cellular function of foiegr/trappc11, and using the zebrafish bearing a mutation in the foiegr gene 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 the development of liver cancer by focusing on the epigenetic regulator, UHRF1. This gene is required for DNA methylation and wehave found that loss of uhrf1 this contributes to a cell cycle defect and apoptosis which prevents hepatic outgrowth in zebrafish embryos. Additionally, UHRF1 is an oncogene in liver cancer and overexpression of UHRF1 in hepatocytes causes DNA hypomethylation and senescence and then when senescence is bypassed, tumors form.
Current Research Studies
- Investigating the role of the unfolded protein response (UPR) in fatty liver disease
- Elucidating the cellular function of Foigr/Trappc11.
- Understanding the role of UHRF1 in regulating the epigenetic basis of liver growth in embryos, regeneration in adults and liver cancer.
- Determining how senescence bypass occurs in epigenetically damaged cells to give rise to cancer.
Mudbhary R, Hoshida Y, Chernyavskaya Y, Jacob V, Villanueva A, Fiel MI, Chen X, Kojima K, Thung S, Bronson RT, Lachenmayer A, Revill K, Alsinet C, Sachidanandam R, Desai A, SenBanerjee S, Ukomadu C, Llovet JM, Sadler KC. UHRF1 overexpression drives DNA hypomethylation and hepatocellular carcinoma. Cancer cell 2014 Feb; 25(2).
Vacaru A, Di Narzo AF, Howarth DL, Tsedensodnom O, Imrie D, Cinaroglu A, Amin S, Hao K, Sadler KC. Molecularly defined unfolded protein response subclasses have distinct correlations with fatty liver disease in zebrafish. Disease Models and Mechanisms 2014; 7(7): 823-35.
Howarth DL, Lindtner C, Vacaru AM, Sachidanandam R, Tsedensodnom O, Vasilkova T, Buettner C, Sadler KC. Activating transcription factor 6 is necessary and sufficient for alcoholic fatty liver disease in zebrafish. PLoS genetics 2014 May; 10(5).
Vacaru AM, Unlu G, Spitzner M, Mione M, Knapik EW, Sadler KC. In vivo cell biology in zebrafish - providing insights into vertebrate development and disease. Journal of cell science 2014 Feb; 127(Pt 3).
Tsedensodnom O, Vacaru AM, Howarth DL, Yin C, Sadler KC. Ethanol metabolism and oxidative stress are required for unfolded protein response activation and steatosis in alcoholic liver disease. Disease models & mechanisms 2013; 6(5): 1213.
Cinaroglu A, Gao C, Imrie D, Sadler KC. Activating transcription factor 6 plays protective and pathological roles in steatosis due to endoplasmic reticulum stress in zebrafish. Hepatology (Baltimore, Md.) 2011 Aug; 54(2).
Chu J, Loughlin EA, Gaur NA, SenBanerjee S, Jacob V, Monson C, Kent B, Oranu A, Ding Y, Ukomadu C, Sadler KC. UHRF1 phosphorylation by cyclin A2/cyclin-dependent kinase 2 is required for zebrafish embryogenesis. Molecular biology of the cell 2012 Jan; 23(1).
Passeri M, Cinaroglu A, Gao C, Sadler KC. Hepatic Steatosis in Response to Acute Alcohol Exposure in Zebrafish Depends Upon SREBP Activation. Hepatology 2008; 49.
Sadler KC, Krahn KN, Gaur NA, Ukomadu C. Liver growth in the embryo and during liver regeneration in zebrafish requires the cell cycle regulator, uhrf1. Proc Natl Acad Sci U S A 2007; 104: 1570-1575.