A5019269730- RNA modifications and cancer
- RNA Research and Splicing
- Fungal and yeast genetics research
- Cancer-related molecular mechanisms research
- DNA Repair Mechanisms
- RNA and protein synthesis mechanisms
- RNA regulation and disease
- CRISPR and Genetic Engineering
- Single-cell and spatial transcriptomics
- Cancer-related gene regulation
- Microtubule and mitosis dynamics
- Amyotrophic Lateral Sclerosis Research
- Bacteriophages and microbial interactions
- RNA Interference and Gene Delivery
- Neuroinflammation and Neurodegeneration Mechanisms
- Cell Image Analysis Techniques
- Neurogenetic and Muscular Disorders Research
- Parkinson's Disease Mechanisms and Treatments
- Gene Regulatory Network Analysis
- Plant Virus Research Studies
- Plant nutrient uptake and metabolism
- Nanoplatforms for cancer theranostics
- Evolution and Genetic Dynamics
- interferon and immune responses
- Cancer Genomics and Diagnostics
Biogen (United States)
2018-2025
Massachusetts Institute of Technology
2008-2019
IIT@MIT
2017-2018
Howard Hughes Medical Institute
2008-2013
Texas A&M University
2005-2011
Center for Cancer Research
2008
Chronic obstructive pulmonary disease and fibrosis have been hypothesized to represent premature aging phenotypes. At times, they cluster in families, but the genetic basis is not understood. We identified rare, frameshift mutations gene for nuclear assembly factor 1, NAF1, a box H/ACA RNA biogenesis factor, fibrosis-emphysema patients. The segregated with short telomere length, low telomerase levels, extrapulmonary manifestations including myelodysplastic syndrome liver disease. A truncated...
Aneuploidy, a chromosome content that is not multiple of the haploid karyotype, associated with reduced fitness in all organisms analyzed to date. In budding yeast aneuploidy causes cell proliferation defects, many different aneuploid strains exhibiting delay G1, cycle stage governed by extracellular cues, growth rate, and events. Here we characterize this G1 delay. We show 10 14 exhibit defect during G1. Furthermore, display entry correlates size additional chromosome. This due delayed...
Abstract Autoantibodies are a hallmark of numerous neurological disorders, including multiple sclerosis, autoimmune encephalitides and neuromyelitis optica. Whilst well understood in peripheral myeloid cells, the pathophysiological significance autoantibody-induced Fc receptor signalling microglia remains unknown, part due to lack robust vivo model. Moreover, application therapeutic antibodies for neurodegenerative disease also highlights importance understanding microglia. Here, we describe...
Microglia are central nervous system (CNS) resident immune cells that have been implicated in neuroinflammatory pathogenesis of a variety neurological conditions. Their manifold context-dependent contributions to neuroinflammation only beginning be elucidated, which can attributed part the challenges studying microglia vivo and lack tractable vitro systems study function. Organotypic brain slice cultures offer tissue-relevant context enables CNS analysis microglial phenotypes has provided...
The cuprizone (CPZ) model is widely used for modeling demyelination in multiple sclerosis (MS) and testing potential remyelination therapies. We integrated single-cell spatial transcriptomics (ST) to fine map the cellular molecular responses during de remyelination. ST revealed global neuroinflammation brain beyond corpus callosum, with region-specific differences. identified oligodendroglia microglia as two major cell types significant transcriptomic changes model. Ligand‒receptor pairing...
Recent advances in spatial transcriptomics (ST) technologies have transformed our ability to profile gene expression while retaining the crucial context within tissues. However, existing ST platforms suffer from high costs, long turnaround times, low resolution, limited coverage, and small tissue capture areas, which hinder their broad applications. Here we present iSCALE, a method that predicts super-resolution automatically annotates cellular-level architecture for large-sized tissues...
ABSTRACT We have determined the genomic sequences of four virulent myophages, Bcep1, Bcep43, BcepB1A, and Bcep781, whose hosts are soil isolates Burkholderia cepacia complex. Despite temporal spatial separations between initial isolations, three phages (Bcep1, designated Bcep781 group) exhibit 87% to 99% sequence identity one another most coding region differences due synonymous nucleotide substitutions, a hallmark neutral genetic drift. Phage BcepB1A has very different genome organization...
ABSTRACT Within the Burkholderia cepacia complex, B. cenocepacia is most common species associated with aggressive infections in lungs of cystic fibrosis patients, causing disease that often refractive to treatment by antibiotics. Phage therapy may be a potential alternative form for these infections. Here we describe genome previously described therapeutic podophage BcepIL02 and its close relative, Bcep22. Bcep22 was found contain circularly permuted 63,882 bp containing 77 genes; 62,714...
SUMMARY Non-coding RNAs contain dozens of chemically distinct modifications, which only a few have been identified in mRNAs. The recent discovery that certain tRNA modifying enzymes also target mRNAs suggests the potential for many additional mRNA modifications. Here, we show conserved 2′-O-methyltransferases Trm3, 7,13 and 44, rRNA 2′-O-methyltransferase Spb1, interact with specific sites yeast by crosslinking immunoprecipitation sequencing (CLIP-seq). We developed methylation at two prime...
Bruton's tyrosine kinase (BTK) plays a non-redundant signaling role downstream of the B-cell receptor (BCR) in B cells and receptors for Fc region immunoglobulins (FcR) myeloid cells. Here, we characterise BIIB091, novel, potent, selective reversible small-molecule inhibitor BTK.BIIB091 was evaluated vitro vivo preclinical models phase 1 clinical trial.In vitro, BIIB091 potently inhibited BTK-dependent proximal distal functional responses both with IC50s ranging from 3 to 106 nm, including...
Abstract A diverse array of post‐transcriptional modifications is found in RNA molecules from all domains life. While the locations are well characterized abundant noncoding RNAs, modified sites less mRNAs just beginning to be discovered. Recent work has revealed hundreds previously unknown and dynamically regulated pseudouridines (Ψ) organisms. This unit describes Pseudo‐seq, an efficient, high‐resolution method for identification Ψs genome‐wide. includes methods isolation S. cerevisiae ,...
Abstract Here, we report the independent discovery and validation of stearoyl-CoA desaturase (SCD) as a modulator α-synuclein (αSyn)-induced pathology toxicity in cell-based Parkinson’s disease (PD) models. We identified SCD top altered gene from transcriptional profiling primary neurons exogenously expressing αSyn with amplified familial PD mutation 3K. Thus, sought to further explore therapeutic target neurodegeneration. that inhibitors are toxic early human rat neuron cultures while...
Toxic gain-of-function mutations in superoxide dismutase 1 (SOD1) contribute to approximately 2%-3% of all amyotrophic lateral sclerosis (ALS) cases. Artificial microRNAs (amiRs) delivered by adeno-associated virus (AAV) have been proposed as a potential treatment option silence SOD1 expression and mitigate disease progression. Primary microRNA (pri-miRNA) scaffolds are used amiRs shuttle hairpin RNA into the endogenous miRNA pathway, but it is unclear whether different primary impact...
Abstract In recent years, High‐Throughput Sequencing (HTS) based methods to detect mutations in biotherapeutic transgene products have become a key quality step deployed during the development of manufacturing cell line clones. Previously we reported on higher throughput, rapid mutation detection method amplicon sequencing (targeting RNA) and detailed its implementation facilitate clone selection. By gaining experience with our assay diverse set programs, improved computational analysis as...