A5007257334- Zebrafish Biomedical Research Applications
- Pancreatic function and diabetes
- Liver Disease Diagnosis and Treatment
- Liver physiology and pathology
- Epigenetics and DNA Methylation
- Hippo pathway signaling and YAP/TAZ
- Renal and related cancers
- Cancer, Hypoxia, and Metabolism
- Birth, Development, and Health
- Hematopoietic Stem Cell Transplantation
- Pregnancy and preeclampsia studies
- Lipid metabolism and biosynthesis
- Mesenchymal stem cell research
- Genetic and Kidney Cyst Diseases
- CRISPR and Genetic Engineering
- Autophagy in Disease and Therapy
- Cancer-related gene regulation
- Renal cell carcinoma treatment
- Mitochondrial Function and Pathology
- Neonatal Health and Biochemistry
- Metabolism and Genetic Disorders
- Organ Transplantation Techniques and Outcomes
- Adipose Tissue and Metabolism
- Pediatric Hepatobiliary Diseases and Treatments
- Pluripotent Stem Cells Research
Harvard University
2016-2025
Broad Institute
2016-2025
Brigham and Women's Hospital
2016-2025
Harvard Stem Cell Institute
2016-2025
Harvard–MIT Division of Health Sciences and Technology
2018-2025
Massachusetts General Hospital
2010-2025
Dana-Farber Cancer Institute
2015-2024
Mass General Brigham
2023
Massachusetts Institute of Technology
2010-2021
Dana-Farber Brigham Cancer Center
2005-2016
Leukemia stem cells (LSCs) are capable of limitless self-renewal and responsible for the maintenance leukemia. Because selective eradication LSCs could offer substantial therapeutic benefit, there is interest in identifying signaling pathways that control their development. We studied mouse models acute myelogenous leukemia (AML) induced either by coexpression Hoxa9 Meis1a oncogenes or fusion oncoprotein MLL-AF9. show Wnt/beta-catenin pathway required derived from hematopoietic (HSC) more...
NCOA4 is a selective cargo receptor for the autophagic turnover of ferritin, process critical regulation intracellular iron bioavailability. However, how ferritinophagy flux controlled and roles in iron-dependent processes are poorly understood. Through analysis NCOA4-FTH1 interaction, we demonstrate that direct association via key surface arginine FTH1 C-terminal element required delivery ferritin to lysosome autophagosomes. Moreover, abundance under dual control autophagy ubiquitin...
Mitochondrial dysfunction is associated with a spectrum of human disorders, ranging from rare, inborn errors metabolism to common, age-associated diseases such as neurodegeneration. How these lesions give rise diverse pathology not well understood, partly because their proximal consequences have been well-studied in mammalian cells. Here we provide two lines evidence that mitochondrial respiratory chain leads alterations one-carbon pathways. First, using hypothesis-generating metabolic,...
Thriving on a breath of low oxygen Mitochondrial diseases are debilitating and largely untreatable. Most caused by genetic mutations that impair the mitochondrial respiratory chain, which generates cellular energy. Because these do not affect all tissues equally, it is thought endogenous mechanisms exist can help cells cope with defects. Jain et al. identified hypoxia response, mechanism helps adapt when limited, as potent suppressor dysfunction (see Perspective Shoubridge). Mouse models...
Embryonal rhabdomyosarcoma (ERMS) is a devastating cancer with specific features of muscle differentiation that can result from mutational activation RAS family members. However, to date, pathway has not been reported in majority ERMS patients. Here, we have created zebrafish model RAS-induced ERMS, which animals develop externally visible tumors by 10 d life. Microarray analysis and cross-species comparisons identified two conserved gene signatures found both human one associated...
Significance The mechanical integrity of the arterial wall is dependent on a properly structured ECM. Elastin and collagen are key structural components ECM, contributing to stability elasticity normal arteries. Lysyl oxidase (LOX) normally cross-links elastin molecules in process forming proper fibers elastic lamellae. Here, using whole-genome sequencing humans genome engineering mice, we show that missense mutation LOX causes aortic aneurysm dissection because insufficient cross-linking...
Acetaminophen (APAP) toxicity is the most common drug-induced cause of acute liver failure in United States. The only available treatment, N-acetylcysteine (NAC), has a limited time window efficacy, indicating need for additional therapeutic options. Zebrafish have emerged as powerful tool drug discovery. Here, we developed clinically relevant zebrafish model APAP toxicity. depleted glutathione stores, elevated aminotransferase levels, increased apoptosis, and caused dose-dependent...
Genetic mapping of mutations in model systems has facilitated the identification genes contributing to fundamental biological processes including human diseases. However, this approach historically required prior characterization informative markers. Here we report a fast and cost-effective method for genetic using next-generation sequencing that combines single nucleotide polymorphism discovery, mutation localization, potential causal sequence variants. In contrast approaches, have...