A5003957317- RNA Research and Splicing
- Genetic Neurodegenerative Diseases
- RNA and protein synthesis mechanisms
- RNA modifications and cancer
- Mitochondrial Function and Pathology
- Muscle Physiology and Disorders
- CRISPR and Genetic Engineering
- Neurogenetic and Muscular Disorders Research
- RNA regulation and disease
- Parkinson's Disease Mechanisms and Treatments
- Amyotrophic Lateral Sclerosis Research
- Cardiomyopathy and Myosin Studies
- Photoreceptor and optogenetics research
- Genetic Associations and Epidemiology
- Prenatal Screening and Diagnostics
- Neuroscience and Neuropharmacology Research
- Lipid Membrane Structure and Behavior
- MicroRNA in disease regulation
- Genetics and Neurodevelopmental Disorders
- Pulmonary Hypertension Research and Treatments
- Cancer-related molecular mechanisms research
- Cerebrospinal fluid and hydrocephalus
- Molecular Biology Techniques and Applications
- Prion Diseases and Protein Misfolding
- Genetics, Aging, and Longevity in Model Organisms
University of Florida
2016-2025
University of Pittsburgh Medical Center
2025
Providence VA Medical Center
2022-2024
Institute of Genetics
2023
Florida College
2016-2023
Emory University
2021
Georgia Institute of Technology
2021
Southern Connecticut State University
2020
University of Maryland, College Park
2018-2019
Massachusetts Institute of Technology
2008-2018
The parts of the genome transcribed by a cell or tissue reflect biological processes and functions it carries out. We characterized features mammalian transcriptomes at gene level through analysis RNA deep sequencing (RNA-Seq) data across human mouse tissues lines. observed that roughly 8,000 protein-coding genes were ubiquitously expressed, contributing to around 75% all mRNAs message copy number in most tissues. These encoded proteins often intracellular, tended be involved metabolism,...
In the face of systemic risk factors, certain regions arterial vasculature remain relatively resistant to development atherosclerotic lesions. The biomechanically distinct environments in these geometries exert a protective influence via key functions endothelial lining; however, mechanisms underlying coordinated regulation specific mechano-activated transcriptional programs leading functional phenotypes have remained elusive. Here, we show that transcription factor Kruppel-like 2 (KLF2) is...
Genomic surveys in humans identify a large amount of recent positive selection. Using the 3.9-million HapMap SNP dataset, we found that selection has accelerated greatly during last 40,000 years. We tested null hypothesis observed age distribution positively selected linkage blocks is consistent with constant rate adaptive substitution human evolution. show high enough to explain number recently variants would predict (i) site heterozygosity at least 10-fold lower than humans, (ii) strong...
By using the 1.6 million single-nucleotide polymorphism (SNP) genotype data set from Perlegen Sciences [Hinds, D. A., Stuve, L. L., Nilsen, G. B., Halperin, E., Eskin, Ballinger, G., Frazer, K. A. & Cox, R. (2005) Science 307, 1072-1079], a probabilistic search for landscape exhibited by positive Darwinian selection was conducted. sorting each high-frequency allele homozygosity, we expected decay of adjacent SNP linkage disequilibrium (LD) at recently selected alleles, eliminating need...
ABSTRACT Objective To develop a novel prenatal assay based on selective analysis of cell‐free DNA in maternal blood for evaluation fetal Trisomy 21 (T21) and 18 (T18). Methods Two hundred ninety‐eight pregnancies, including 39 T21 seven T18 confirmed aneuploidies, were analyzed using novel, highly multiplexed assay, termed digital selected regions (DANSR™). Cell‐free from samples was DANSR assays loci chromosomes 18. Products 96 separate patients pooled sequenced together. A standard Z ‐test...
We set out to develop a molecular test that distinguishes benign and malignant thyroid nodules using fine-needle aspirates (FNA).We used mRNA expression analysis measure more than 247,186 transcripts in 315 nodules, comprising multiple subtypes. The data consisted of 178 retrospective surgical tissues 137 prospectively collected FNA samples. Two classifiers were trained separately on FNAs. performance was evaluated an independent 48 prospective samples, which included 50% with indeterminate...
Significance The effectiveness of nucleic acid drugs is limited by inefficient delivery to target tissues and cells unwanted accumulation in off-target organs. Although thousands chemically distinct nanoparticles can be synthesized, designed deliver acids vivo were first tested cell culture, yielding poor predictions for vivo. To facilitate testing many vivo, we optimized a high-throughput DNA barcoding system simultaneously measure mediated dozens single mouse. This nano-barcoding used...
RNA binding proteins of the conserved CUGBP1, Elav-like factor (CELF) family contribute to heart and skeletal muscle development are implicated in myotonic dystrophy (DM). To understand their genome-wide functions, we analyzed transcriptome dynamics following induction CELF1 or CELF2 adult mouse by RNA-seq, complemented crosslinking/immunoprecipitation-sequencing (CLIP-seq) analysis cells tissues distinguish direct from indirect regulatory targets. We identified hundreds mRNAs bound 3′ UTRs...
Abstract Motivation: Analysis of RNA sequencing (RNA-Seq) data revealed that the vast majority human genes express multiple mRNA isoforms, produced by alternative pre-mRNA splicing and other mechanisms, most isoforms vary in expression between tissues. As RNA-Seq datasets grow size, it remains challenging to visualize isoform across samples. Results: To help address this problem, we present Sashimi plots, a quantitative visualization aligned reads enables comparison exon usage samples or...
Abstract Myotonic dystrophy (DM) is caused by the expression of mutant RNAs containing expanded CUG repeats that sequester muscleblind-like (MBNL) proteins, leading to alternative splicing changes. Cardiac alterations, characterized conduction delays and arrhythmia, are second most common cause death in DM. Using RNA sequencing, here we identify novel alterations DM heart samples, including a switch from adult exon 6B towards fetal 6A cardiac sodium channel, SCN5A . We find MBNL1 regulates...
As the area of small molecules interacting with RNA advances, general routes to provide bioactive compounds are needed as ligands can bind avidly sites that will not affect function. Small-molecule targeted degradation thus a route biology. A non–oligonucleotide-containing compound was designed from sequence target precursor oncogenic microRNA-21 (pre–miR-21) for enzymatic destruction selectivity exceed protein-targeted medicines. The specifically binds and contains heterocycle recruits...
Local patterns of biomechanical forces experienced by endothelial cells (ECs) in different vascular geometries appear to play an essential role regulating EC function and determining the regional susceptibility atherosclerosis, even face systemic risk factors. To study how regulate redox homeostasis, important pathogenic factor atherogenesis, we have cultured human ECs under 2 prototypic arterial shear stress waveforms, “atheroprone” “atheroprotective,” which were derived from distinct...
Article15 May 2018Open Access Source DataTransparent process Mice with endogenous TDP-43 mutations exhibit gain of splicing function and characteristics amyotrophic lateral sclerosis Pietro Fratta Corresponding Author [email protected] orcid.org/0000-0002-8762-8188 UCL Institute Neurology, MRC Centre for Neuromuscular Disease, London, UK Search more papers by this author Prasanth Sivakumar Jack Humphrey Genetics Institute, Kitty Lo Thomas Ricketts Mammalian Unit, Harwell, Hugo Oliveira Jose...
Recent genome-wide analyses have elucidated the extent of alternative splicing (AS) in mammals, often focusing on comparisons splice isoforms between differentiated tissues.However, regulated changes are likely to be important biological transitions such as cellular differentiation, or response environmental stimuli.To assess and significance AS myogenesis, we used splicing-sensitive microarray analysis differentiating C2C12 myoblasts.We identified 95 events that undergo robust during...
Myotonic dystrophy type 1 (DM1) is a triplet repeating disorder caused by expanded CTG repeats in the 3′-untranslated region of dystrophia myotonica protein kinase (DMPK) gene. The transcribed fold into an RNA hairpin with multiple copies 5′CUG/3′GUC motif that binds splicing regulator muscleblind-like (MBNL1). Sequestration MBNL1 r(CUG) causes defects subset pre-mRNAs including insulin receptor, muscle-specific chloride ion channel, sarco(endo)plasmic reticulum Ca2+ ATPase 1, and cardiac...
Abstract Myotonic dystrophy (dystrophia myotonica, DM) is a multi-systemic disease caused by expanded CTG or CCTG microsatellite repeats. Characterized symptoms in muscle, heart and central nervous system, among others, it one of the most variable diseases known. A major pathogenic event DM sequestration muscleblind-like proteins CUG CCUG repeat-containing RNAs transcribed from repeats, differences extent MBNL dependent on repeat length expression level may account for some portion...