A5026230810- CRISPR and Genetic Engineering
- MicroRNA in disease regulation
- Cancer-related molecular mechanisms research
- Genomics and Chromatin Dynamics
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Muscle Physiology and Disorders
- Nutrition and Health in Aging
- Epigenetics and DNA Methylation
- RNA Interference and Gene Delivery
- Genetics and Neurodevelopmental Disorders
- Congenital Anomalies and Fetal Surgery
- Heat shock proteins research
- Chromosomal and Genetic Variations
- Osteoarthritis Treatment and Mechanisms
- Muscle metabolism and nutrition
- Cellular transport and secretion
- Cell death mechanisms and regulation
- RNA modifications and cancer
- Prenatal Screening and Diagnostics
- Growth Hormone and Insulin-like Growth Factors
- RNA and protein synthesis mechanisms
- Nasal Surgery and Airway Studies
- Single-cell and spatial transcriptomics
- Protein Degradation and Inhibitors
- interferon and immune responses
Harvard University
2015-2025
Massachusetts General Hospital
2015-2025
Howard Hughes Medical Institute
1999-2017
Vanderbilt University
2011-2017
Massachusetts Institute of Technology
1999
Protein partners for chromosome silencing Female mammals have two X chromosomes, one of which is almost completely shut down during development. The long noncoding Xist RNA plays a role in this process. To understand how whole can be stably inactivated, Minajigi et al. identified many the proteins that bind to RNA, include cohesins. Paradoxically, interaction between and cohesin subunits resulted repulsion complexes from inactive chromosome, changing three-dimensional shape chromosome....
Highlights•Epigenomic mapping shows that mouse TERRA RNA binds telomeres and select genes•iDRiP proteomics reveals ATRX is a major TERRA-interacting protein•TERRA antagonize each other functionally•Loss of results in telomere dysfunction instabilitySummaryThrough an integration genomic proteomic approaches to advance understanding long noncoding RNAs, we investigate the function telomeric transcript, TERRA. By identifying thousands target sites genome, demonstrate can bind both cis trans...
During early vertebrate development, a large number of noncoding RNAs are maternally inherited or expressed upon activation zygotic transcription. The exact identity, expression levels, and function for most these remain largely unknown. miRNAs (microRNAs) piRNAs (piwi-interacting RNAs) two classes small that play important roles in gene regulation during embryonic development. Here, we utilized next-generation sequencing technology to determine temporal patterns both four distinct stages...
Significance The X-chromosome harbors hundreds of disease genes, a subset which gives rise to neurodevelopmental disorders such as Rett syndrome (RTT), fragile X syndrome, and CDKL5 syndrome. There is presently no disease-specific treatment. Here, we work toward therapeutic program based on reactivation the silent chromosome restore expression missing protein. We develop mixed modality approach that combines small-molecule inhibitor DNA methylation an antisense oligonucleotide against Xist...
SNAP-25 is a core component of the trimeric SNARE complex mediating vesicle exocytosis during membrane addition for neuronal growth, neuropeptide/growth factor secretion, and neurotransmitter release synaptic transmission. Here, we report novel microRNA mechanism regulation controlling motor neuron development, neurosecretion, activity, movement in zebrafish. Loss miR-153 causes overexpression consequent hyperactive early zebrafish embryos. Conversely, down resulting near complete paralysis,...
Three genes-reaper, grim, and hid-are crucial to the regulation of programmed cell death in Drosophila melanogaster. Mutations involving all three genes virtually abolish apoptosis during development, homozygous hid mutants die as embryos with extensive defects apoptosis. Although Hid is central Drosophila, it has no mammalian homologue identified date. We present evidence that expression cells induces This activity subject by inhibitors death. show N terminus Hid, which a region homology...
Progressive loss of skeletal muscle, termed muscle wasting, is a hallmark cancer cachexia and contributes to weakness, reduced quality life, as well poor response therapy. Previous studies have indicated that systemic host inflammatory regarding tumor development results in wasting. However, how directly regulates wasting via tumor-derived secreted proteins still largely unknown. In this study, we performed bioinformatics analysis two datasets pancreatic ductal adenocarcinoma, which causes...
Significance In mammalian female cells, nearly all genes are silenced on one of two X chromosomes. Heterozygous females with “dominant” X-linked diseases, such as Rett syndrome, may benefit from pharmacological reactivation the silent, healthy allele in affected organs. Toward establishing proof concept, here we carry out a primed screen large library small molecules for compounds that can reactivate expression inactive (Xi). We identify combination inhibits DNA methylation and Aurora kinase...
microRNAs (miRNAs) are a family of 21-23 nucleotide endogenous non-coding RNAs that post-transcriptionally regulate gene expression in sequence-specific manner. Typically, miRNAs downregulate target genes by recognizing and recruiting protein complexes to 3'UTRs, followed translation repression or mRNA degradation. miR-92 is well-studied oncogene mammalian systems. Here, using zebrafish as model system, we uncovered novel tissue-inductive role for during early vertebrate development....
RNAi based strategies to induce gene silencing are commonly employed in numerous model organisms but have not been extensively used zebrafish. We found that introduction of transgenes containing convergent transcription units zebrafish embryos induced stable transcriptional (TGS) cis and trans for reporter (mCherry) endogenous (One-Eyed Pinhead (OEP) miR-27a/b) genes. Convergent enabled detection both sense antisense transcripts was suppressed upon Dicer knockdown, indicating processing...
Mammalian cells equalize X-linked dosages between the male (XY) and female (XX) sexes by silencing one X chromosome in sex. This process, known as "X inactivation" (XCI), requires a master switch within inactivation center (
Cranial neural crest cells are a multipotent cell population that generate all the elements of pharyngeal cartilage with differentiation into chondrocytes tightly regulated by temporal intracellular and extracellular cues. Here, we demonstrate novel role for miR-27, highly enriched microRNA in arches, as positive regulator chondrogenesis. Knock down miR-27 led to nearly complete loss attenuating proliferation blocking pre-chondrogenic cells. Focal adhesion kinase (FAK) is key...
ABSTRACT In mammals, X-linked dosage compensation involves two processes: X-chromosome inactivation (XCI) to balance X chromosome between males and females, hyperactivation of the remaining (Xa-hyperactivation) achieve X-autosome in both sexes. Studies processes have largely focused on coding genes not accounted for transposable elements (TEs) which comprise 50% X-chromosome, despite TEs being suspected numerous epigenetic functions. This oversight is due part technical challenge capturing...