A5010589331- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Medical Imaging and Pathology Studies
- Genomic variations and chromosomal abnormalities
- Chromosomal and Genetic Variations
- Congenital heart defects research
- Pneumonia and Respiratory Infections
- Occupational and environmental lung diseases
- Lung Cancer Treatments and Mutations
- Peptidase Inhibition and Analysis
- Cystic Fibrosis Research Advances
- Glycosylation and Glycoproteins Research
- RNA and protein synthesis mechanisms
- Systemic Sclerosis and Related Diseases
- Epigenetics and DNA Methylation
- Renal Diseases and Glomerulopathies
- Psychedelics and Drug Studies
- Banana Cultivation and Research
- Lung Cancer Research Studies
- Protein Tyrosine Phosphatases
- Neurofibromatosis and Schwannoma Cases
- Complementary and Alternative Medicine Studies
- Biochemical and Molecular Research
- Inhalation and Respiratory Drug Delivery
- Wheat and Barley Genetics and Pathology
- Biochemical Analysis and Sensing Techniques
Mass General Brigham
2018-2023
University of Colorado Denver
2012-2016
Imperial College London
2014
Framingham Heart Study
2013
Brigham and Women's Hospital
2013
National Heart Lung and Blood Institute
2013
Harvard University
2008
State Hospital
1943
Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease of unknown cause that leads to respiratory failure and death within 5 years diagnosis. Overt infection immunosuppression carry high morbidity mortality, polymorphisms in genes related epithelial integrity host defense predispose IPF.To investigate the role bacteria pathogenesis progression IPF.We prospectively enrolled patients diagnosed with IPF according international criteria together healthy smokers, nonsmokers, subjects...
<h3>Importance</h3>Current prediction models of mortality in idiopathic pulmonary fibrosis (IPF), which are based on clinical and physiological parameters, have modest value predicting patients will progress. In addition to the potential for improving prognostic models, identifying genetic molecular features that associated with IPF may provide insight into underlying mechanisms disease inform trials.<h3>Objective</h3>To determine whether MUC5B promoter polymorphism (rs35705950), previously...
A common promoter polymorphism (rs35705950) in MUC5B, the gene encoding mucin 5B, is associated with idiopathic pulmonary fibrosis. It not known whether this interstitial lung disease general population.We performed a blinded assessment of abnormalities detected 2633 participants Framingham Heart Study by means volumetric chest computed tomography (CT). We evaluated relationship between and genotype at rs35705950 locus.Of CT scans that were evaluated, present 177 (7%). Participants such more...
Idiopathic pulmonary fibrosis (IPF) is an untreatable lung disease with a median survival of only 3-5 years that diagnosed using combination clinical, radiographic and pathologic criteria. Histologically, IPF characterised by usual interstitial pneumonia (UIP), fibrosing pattern heterogeneous, subpleural regions fibrotic remodelled lung. We hypothesised gene expression profiles tissue may identify molecular subtypes could classify IPF/UIP have clinical implications.We collected...
Rationale: Up to 20% of cases idiopathic interstitial pneumonia cluster in families, comprising the syndrome familial (FIP); however, genetic basis FIP remains uncertain most families.Objectives: To determine if new disease-causing rare variants could be identified using whole-exome sequencing affected members from providing additional insights into disease pathogenesis.Methods: Affected subjects 25 kindreds were selected an ongoing registry for genomic DNA. Candidate confirmed by Sanger...
Idiopathic pulmonary fibrosis (IPF) is an untreatable and often fatal lung disease that increasing in prevalence caused by complex interactions between genetic environmental factors. Epigenetic mechanisms control gene expression are likely to regulate the IPF transcriptome.
Fibrotic idiopathic interstitial pneumonias (fIIP) are a group of fatal lung diseases with largely unknown etiology and without definitive treatment other than transplant to prolong life. There is strong evidence for the importance both rare common genetic risk alleles in familial sporadic disease. We have previously used genome-wide single nucleotide polymorphism data identify 10 loci fIIP. Here we extend that work imputed genotypes conduct new RNA sequencing studies tissue characterize...
Tuberculosis remains a major global health problem that kills up to 2 million people annually. Central the success of Mycobacterium tuberculosis ( Mtb ) as pathogen is its ability evade host immunity and establish chronic infection. Although primary intracellular niche within macrophages, underlying molecular mechanisms are poorly understood. Here we show Rv2224c, cell envelope-associated predicted protease, critical for virulence. Disruption Rv2224c led prolonged survival infected mice...
Copy number variants (CNVs) can substantially contribute to the pathogenic variant spectrum in several disease genes. The detection of this type is complicated genes with high homology other genomic sequences, yet such genomics regions are more likely lead CNVs, making it critical address these settings.We developed a copy analysis approach for genes/regions that consisted next-generation sequencing (NGS)-based dosage accompanied by allele-specific droplet digital PCR (ddPCR) confirmatory...
Idiopathic interstitial pneumonias (IIPs) are a group of heterogeneous, somewhat unpredictable diseases characterized by progressive scarring the interstitium. Since lung function is key determinant survival, we reasoned that transcriptional profile in IIP tissue would be associated with measures function, and could enhance prognostic approaches to IIPs. Using gene expression profiling 167 specimens diagnosis 50 control lungs, identified genes whose changes (% predicted FVC % DLCO) modeled...
Bi-allelic loss-of-function variants of OTOA are a well-known cause moderate-to-severe hearing loss. Whereas non-allelic homologous recombination-mediated deletions the gene well known, conversions to pseudogene OTOAP1 have been reported in literature but never fully described nor their pathogenicity assessed. Here, we report two unrelated patients with moderate hearing-loss, who were compound heterozygotes for converted allele and deletion OTOA. The initially detected through sequencing...
Hunninghake, Gary M.*†; Hatabu, Hiroto‡§; Okajima, Yuka‡§; Gao, Wei∥¶; Dupuis, Josée∥¶; Latourelle, Jeanne C.#; Nishino, Mizuki‡§; Araki, Tetsuro‡§; Zazueta, Oscar E.*†; Kurugol, Sila**; Ross, James C.**††; Estépar, Raúl San José§**; Murphy, Elissa‡‡; Steele, Mark P.§§; Loyd, E.§§; Schwarz, Marvin I.‡‡; Fingerlin, Tasha E.∥∥; Rosas, Ivan O.*†; Washko, George R.*†; O’Connor, T.¶¶¶; Schwartz, David A.‡‡ Author Information
Abstract Background RASopathies are a group of disorders caused by disruptions to the RAS‒MAPK pathway. Despite being in same pathway, Neurofibromatosis Type 1 (NF1) and Legius syndrome (LS) typically present with phenotypes distinct from Noonan spectrum (NSDs). However, some NF1/LS individuals also exhibit NSD phenotypes, often referred as Neurofibromatosis‐Noonan (NFNS), may be mistakenly evaluated for NSDs, delaying diagnosis, affecting patient management. Methods A derivation cohort 28...
Background Mutations in Surfactant Protein C (SFTPC) can lead to fibrotic interstitial lung disease (ILD) with variable phenotypes, especially children. The sources of phenotype variability are incompletely understood. A common MUC5B promoter variant rs35705950 is associated adult Idiopathic Pulmonary Fibrosis (IPF). We examined whether similarly linked ILD secondary SFTPC mutations. Methods concentration bronchoalveolar lavage fluid (BALF) was measured six pediatric patients mutations and...
Biallelic deletions at 15q15.3, including STRC and CATSPER2, cause autosomal recessive deafness-infertility syndrome (DIS), while biallelic of alone nonsyndromic hearing loss. These are among the leading genetic causes mild-moderate loss, but their detection using chromosomal microarray (CMA) is impeded by a tandem duplication containing highly homologous pseudogenes. We sought to assess copy number variant (CNV) in this region commonly-employed CMA platform.Twenty-two specimens with known...
ABSTRACT Summary Molecular inversion probes (MIP’s) allow efficient enrichment of genomic regions interest for the purpose targeted sequencing. To date, there is a paucity simple-to-use software to align sequences derived from this method. Here, we describe single program that performs mapping, arm removal, and deduplication before outputting alignments in SAM format. Availability bwa-mips available at https://github.com/brentp/bwa-mips under MIT license. Contact bpederse@gmail.com
Sparsentan, a first-in-class, orally active, dual-acting, selective antagonist of the angiotensin II type 1 receptor and endothelin A receptor, is in development for treatment focal segmental glomerulosclerosis (FSGS). In ongoing DUET trial patients with FSGS, sparsentan 200, 400, 800 mg/d resulted greater reduction proteinuria versus irbesartan 300 over an 8-week double-blind period. Sparsentan continues to be evaluated open-label extension (OLE) trial.
To develop a regulatory T cell (Treg)-based therapy for the treatment of progressive multiple sclerosis (MS).