A5037437791- RNA modifications and cancer
- Cancer-related molecular mechanisms research
- RNA Research and Splicing
- Renal and related cancers
- Cancer-related gene regulation
- Erythrocyte Function and Pathophysiology
- Pancreatic function and diabetes
- Endoplasmic Reticulum Stress and Disease
- Aquatic life and conservation
- Pluripotent Stem Cells Research
- Diabetes Management and Research
- Galectins and Cancer Biology
- Diet, Metabolism, and Disease
- Wnt/β-catenin signaling in development and cancer
- Pregnancy and preeclampsia studies
- Renal cell carcinoma treatment
- Birth, Development, and Health
- Developmental Biology and Gene Regulation
- Congenital Diaphragmatic Hernia Studies
- Acute Myeloid Leukemia Research
- Neonatal Respiratory Health Research
- Congenital heart defects research
- Acute Lymphoblastic Leukemia research
- Hemoglobinopathies and Related Disorders
- Immune Cell Function and Interaction
Dana-Farber Cancer Institute
2015-2025
Broad Institute
2024
Boston Children's Hospital
2014-2022
Harvard University
2013-2021
Harvard Stem Cell Institute
2014-2019
Howard Hughes Medical Institute
2014-2019
Boston Children's Museum
2015
Preservation of insulin-producing pancreatic β cells in type 1 diabetes requires an intact UPR, and treatment with tauroursodeoxycholic acid can restore UPR defects.
Wilms Tumor, the most common pediatric kidney cancer, evolves from failure of terminal differentiation embryonic kidney. Here we show that overexpression heterochronic regulator Lin28 during development in mice markedly expands nephrogenic progenitors by blocking their final wave differentiation, ultimately resulting a pathology highly reminiscent tumor. Using lineage-specific promoters to target specific cell types, observed tumor only when is aberrantly expressed multiple derivatives...
Colorectal cancer (CRC) remains a major contributor to cancer-related mortality. LIN28A and LIN28B are highly related RNA-binding protein paralogs that regulate biogenesis of let-7 microRNAs influence development, metabolism, tissue regeneration, oncogenesis. Here we demonstrate overexpression either LIN28 paralog cooperates with the Wnt pathway promote invasive intestinal adenocarcinoma in murine models. When alone is induced genetically, half resulting tumors harbor Ctnnb1 (β-catenin)...
The endoplasmic reticulum adapts to fluctuations in demand and copes with stress through an adaptive signaling cascade called the unfolded protein response (UPR). Accumulating evidence indicates that canonical UPR is critical survival function of insulin-producing pancreatic β-cells alterations may contribute pathogenesis type 2 diabetes. However, dynamic regulation molecules islets animal models humans diabetes remains be elucidated. Here, we analyzed expression activating factor 6 (ATF6α)...
Abstract In humans and in mice the formation of nephrons during embryonic development reaches completion near end gestation, after which no new are formed. The final nephron complement can vary 10-fold, with reduced number predisposing individuals to hypertension, renal, cardiovascular diseases later life. While heterochronic genes lin28 let-7 well-established regulators developmental timing invertebrates, their role mammalian organogenesis is not fully understood. Here we report that...
Leukemia phenotypes vary with age of onset. Delineating mechanisms specificity in leukemia could improve disease models and uncover new therapeutic approaches. Here, we used heterochronic transplantation driven by MLL/KMT2A translocations to investigate the contribution hematopoietic microenvironment age-specific phenotypes. When MLL-AF9, cells adult sustained a myeloid phenotype, whereas neonatal supported genesis mixed early B cell/myeloid leukemia. In MLL-ENL leukemia, potentiated...
Selective RNA degradation during terminal erythropoiesis results in a globin-rich transcriptome mature erythrocytes, but the specific decay pathways remain unknown. We found that deficiency of uridylyl transferase enzyme Zcchc6 and 3'-5' exoribonuclease Dis3l2 mouse models led to fetal perinatal reticulocytosis, an accumulation RNA-rich precursors erythroid cells, suggesting their crucial roles red cell differentiation. Notably, knockout embryos exhibited persistent high-level expression...
Selective RNA degradation during terminal erythropoiesis results in a globin-rich transcriptome mature erythrocytes, but the specific decay pathways remain unknown. We found that deficiency of uridylyl transferase enzyme Zcchc6 and 3'-5' exoribonuclease Dis3l2 mouse models led to fetal perinatal reticulocytosis, an accumulation RNA-rich precursors erythroid cells, suggesting their crucial roles red cell differentiation. Notably, knockout embryos exhibited persistent high-level expression...
CMTR2 is an mRNA cap methyltransferase with poorly understood physiological functions. It catalyzes 2'-O-ribose methylation of the second transcribed nucleotide mRNAs, potentially serving to mark RNAs as "self" evade cellular innate immune response. Here we analyze consequences Cmtr2 deficiency in mice. We discover that constitutive deletion results mouse embryos die during mid-gestation, exhibiting defects embryo size, placental malformation and yolk sac vascularization. Endothelial cell...
An amendment to this paper has been published and can be accessed via a link at the top of paper.
Abstract Despite extensive investigation into the molecular basis of tumor development, colorectal cancer (CRC) remains a major contributor to cancer-related mortality. LIN28A and LIN28B are highly related RNA-binding proteins that influence tissue regeneration oncogenesis. Here we demonstrate overexpression LIN28 drives invasive intestinal adenocarcinoma cooperates with Wnt pathway promote initiation progression in murine models. Importantly, conditional withdrawal reduced volume increased...
Abstract Cancer genome sequencing studies have identified multiple novel tumor suppressor genes, including the FTSJD1 or CMTR2 gene that is subject to statistically significant levels of both nonsense and frameshift mutations in lung adenocarcinoma. However, these analyses are insufficient determine importance modes action disease. Follow-up functional essential elucidate functions. The protein product has been described as an mRNA cap methyltransferase, which O-methylates ribose second...