Kirsten Sadler Edepli, PhD
- ADJUNCT ASSOCIATE PROFESSOR | Medicine, Liver Diseases
Research Topics:Cancer, Cell Biology, Developmental Biology, Diabetes, Embryology, Genetics, Liver, Morphogenesis, Obesity, Organogenesis, Oxidative Stress, Regeneration, Tumorigenesis
Our laboratory studies the epigenetic regulation of liver development and liver cancer and the relationship between ER stress, the unfolded protein response and fatty liver disease. We use zebrafish, cell biological and genomic approaches to uncover the fundamental biological processes that govern these phenotypes. For detailed information, please consult our lab website.
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.
BA, Mount Holyoke College
MMSc, Harvard Medical School
PhD, Harvard University
fellowship, Massachusetts Institute of Technology
Harold and Golden Lamport Award
Basil O'Connor Starter Scholar Award
Research Scholar Award
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.