Joy D. Cogan
A5009935328- Genomics and Rare Diseases
- Pulmonary Hypertension Research and Treatments
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Growth Hormone and Insulin-like Growth Factors
- Genetics and Neurodevelopmental Disorders
- Medical Imaging and Pathology Studies
- Genomic variations and chromosomal abnormalities
- Congenital heart defects research
- RNA modifications and cancer
- RNA and protein synthesis mechanisms
- RNA Research and Splicing
- Cancer, Hypoxia, and Metabolism
- Metabolism and Genetic Disorders
- RNA regulation and disease
- Cancer-related gene regulation
- Telomeres, Telomerase, and Senescence
- Cancer Genomics and Diagnostics
- Cellular transport and secretion
- Genetic Syndromes and Imprinting
- Mitochondrial Function and Pathology
- Occupational and environmental lung diseases
- Muscle Physiology and Disorders
- MicroRNA in disease regulation
- Neurogenetic and Muscular Disorders Research
- Sexual Differentiation and Disorders
Vanderbilt University Medical Center
2015-2025
Pediatrics and Genetics
2009-2025
Howard Hughes Medical Institute
1998-2024
The University of Texas Southwestern Medical Center
2024
Vanderbilt University
2013-2023
University School of Nashville
2023
Institut thématique Génétique, génomique et bioinformatique
2014-2022
University of California System
2022
Vanderbilt Health
2020-2021
Indiana University School of Medicine
2021
Idiopathic pulmonary fibrosis is progressive and often fatal; causes of familial clustering the disease are unknown. Germ-line mutations in genes hTERT hTR, encoding telomerase reverse transcriptase RNA, respectively, cause autosomal dominant dyskeratosis congenita, a rare hereditary disorder associated with premature death from aplastic anemia fibrosis.To test hypothesis that idiopathic may be caused by short telomeres, we screened 73 probands Vanderbilt Familial Pulmonary Fibrosis Registry...
Idiopathic interstitial pneumonias (IIPs) have a progressive and often fatal course, their enigmatic etiology has complicated approaches to effective therapies. pulmonary fibrosis (IPF) is the most common of IIPs shares with an increased incidence age unexplained scarring in lung. Short telomeres limit tissue renewal capacity lung germ-line mutations telomerase components, hTERT hTR , underlie inheritance subset families IPF. To examine hypothesis that short contribute disease risk sporadic...
Genetic association studies often examine features independently, potentially missing subpopulations with multiple phenotypes that share a single cause. We describe an approach aggregates on the basis of patterns described by Mendelian diseases. mapped clinical 1204 diseases into captured from electronic health record (EHR) and summarized this evidence as phenotype risk scores (PheRSs). In initial validation, PheRS distinguished cases controls five Applying to 21,701 genotyped individuals...
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...
Nucleic acid-sensing Toll-like receptors (TLR) 3, 7/8, and 9 are key innate immune sensors whose activities must be tightly regulated to prevent systemic autoimmune or autoinflammatory disease virus-associated immunopathology. Here, we report a systematic scanning-alanine mutagenesis screen of all cytosolic luminal residues the TLR chaperone protein UNC93B1, which identified both negative positive regulatory regions affecting TLR3, TLR7, TLR9 responses. We subsequently two families harboring...
Mutations in bone morphogenetic protein receptor type 2 ( BMPR2 ) cause familial pulmonary arterial hypertension (FPAH), but the penetrance is reduced and females are significantly overrepresented. In addition, gene expression data implicating oestrogen-metabolising enzyme CYP1B1 suggests a detrimental role of oestrogens or oestrogen metabolites. We examined genetic metabolic markers altered metabolism subjects with mutation. Genotypes for Asn453Ser N453S were determined 140 mutation...
Previous studies have shown that approximately 55% of patients with familial pulmonary arterial hypertension (FPAH) BMPR2 coding sequence mutations. However, direct sequencing does not detect other types heterozygous mutations, such as exonic deletions/duplications.To estimate the frequency deletions/duplications in FPAH.BMPR2 mRNA from lymphoblastoid cell lines 30 families PAH and 14 idiopathic (IPAH) was subjected to reverse transcriptase-polymerase chain reaction (RT-PCR) sequencing....
Asymptomatic relatives of patients with familial interstitial pneumonia (FIP), the inherited form idiopathic pneumonia, carry increased risk for developing lung disease.Studying these at-risk individuals provides a unique opportunity to investigate early stages FIP pathogenesis and develop predictive models disease onset.Seventy-five asymptomatic first-degree (mean age, 50.8 yr) underwent blood sampling high-resolution chest computed tomography (HRCT) scanning in an ongoing cohort study; 72...
Recent studies have shown that disease-susceptibility variants frequently lie in cell-type-specific enhancer elements. To identify, interpret, and prioritize such risk variants, we must identify the enhancers active disease-relevant cell types, their upstream transcription factor (TF) binding, downstream target genes. address this need, built HACER (http://bioinfo.vanderbilt.edu/AE/HACER/), an atlas of Human ACtive Enhancers to interpret Regulatory variants. The catalogues annotates in-vivo...
Rationale: Several common and rare genetic variants have been associated with idiopathic pulmonary fibrosis, a progressive fibrotic condition that is localized to the lung.Objectives: To develop an integrated understanding of located in multiple loci reported contribute risk disease.Methods: We performed deep targeted resequencing (3.69 Mb DNA) cases (n = 3,624) control subjects 4,442) across genes regions previously disease. tested for associations between disease 1) individual via logistic...
Rationale: The preclinical natural history of progressive lung fibrosis is poorly understood.Objectives: Our goals were to identify risk factors for interstitial abnormalities (ILA) on high-resolution computed tomography (HRCT) scans and determine progression toward clinical disease (ILD) among subjects in a longitudinal cohort self-reported unaffected first-degree relatives patients with familial pneumonia.Methods: Enrollment evaluation included health exposure questionnaire HRCT scans,...
Abstract While exome sequencing (ES) is commonly the final diagnostic step in clinical genetics, it may miss diagnoses. To clarify limitations of ES, we investigated yield genetic tests beyond ES our Undiagnosed Diseases Network (UDN) participants. We reviewed additional testing including genome (GS), copy number variant (CNV), noncoding (NCV), repeat expansion (RE), or methylation UDN cases with nondiagnostic results. Overall, 36/54 (67%) total diagnoses were based on findings and coding...
Combined pituitary hormone deficiency (CPHD) has an incidence of approximately 1 in 8000 births. Although the proportion familial CPHD cases is unknown, about 10% have affected first degree relative. We recently reported three mutations PROP1 gene that cause human subjects. report here frequency one these mutations, a 301–302delAG deletion exon 2 PROP1, 10 independently ascertained kindreds and 21 sporadic from 8 different countries. Our results show 55% (11 20) alleles cases. Interestingly,...
Cytosolic phospholipase A2alpha (cPLA2alpha) hydrolyzes arachidonic acid from cellular membrane phospholipids, thereby providing enzymatic substrates for the synthesis of eicosanoids, such as prostaglandins and leukotrienes. Considerable understanding cPLA2alpha function has been derived investigations enzyme cPLA2alpha-null mice, but knowledge discrete roles this in humans is limited. We investigated a patient hypothesized to have an inherited prostanoid biosynthesis deficiency due his...
While BMPR2 mutation strongly predisposes to pulmonary arterial hypertension (PAH), only 20% of carriers develop clinical disease. This finding suggests that modifier genes contribute FPAH expression. Since modifiers are likely be common alleles, this problem is not tractable by traditional genetic approaches. Furthermore, examination gene expression complicated confounding effects attributable drugs and the disease process itself.To resolve these problems, B-cells were isolated,...