A5049814810- Cleft Lip and Palate Research
- Craniofacial Disorders and Treatments
- Toxic Organic Pollutants Impact
- Effects and risks of endocrine disrupting chemicals
- Carcinogens and Genotoxicity Assessment
- Epigenetics and DNA Methylation
- dental development and anomalies
- Congenital Anomalies and Fetal Surgery
- Congenital Ear and Nasal Anomalies
- Air Quality and Health Impacts
- Birth, Development, and Health
- Statistical Methods and Inference
- Tracheal and airway disorders
- Advanced Causal Inference Techniques
- Genomic variations and chromosomal abnormalities
- Neurogenetic and Muscular Disorders Research
- Glycogen Storage Diseases and Myoclonus
- Endometriosis Research and Treatment
- Genomics and Rare Diseases
- RNA modifications and cancer
- Thyroid Disorders and Treatments
- RNA regulation and disease
- Genital Health and Disease
- Genetics and Neurodevelopmental Disorders
- Genetic Syndromes and Imprinting
Emory University
2018-2025
Graduate School USA
2019
Duke University Hospital
2011-2013
Duke Medical Center
2011-2013
Duke University
2011
Brigham and Women's Hospital
2004
Harvard University
2004
Recent trends in prostate needle biopsy reporting have resulted the inclusion of more information and new diagnostic categories. The goal current study was to survey surgical Members Society Urologic Oncology determine what academic urologists consider important management their cancer (PCa) patients. A questionnaire developed investigate several areas PCa reporting, which vary from institution institution. Urologists were sent questionnaires asked return anonymous responses; 42 completely...
Michigan residents were directly exposed to endocrine-disrupting compounds, polybrominated biphenyl (PBB) and polychlorinated (PCB). A growing body of evidence suggests that exposure certain compounds may affect thyroid function, especially in people as children, but there are conflicting observations. In this study, we extend previous work by examining age exposure's effect on the relationship between PBB function a large group individuals PBB. Linear regression models used test association...
In 1973, Michigan residents were exposed to polybrominated biphenyl (PBB) when it was accidentally added farm animal feed. Highly individuals and their children have experienced endocrine-related health problems, though the underlying mechanism behind these remains unknown. We investigated whether PBB exposure is associated with variation in DNA methylation peripheral blood samples from 658 participants of registry using MethylationEPIC BeadChip, as well what potential function affected...
Orofacial clefts (OFCs) are common birth defects including cleft lip, lip and palate, palate. OFCs have heterogeneous etiologies, complicating clinical diagnostics because it is not always apparent if the cause Mendelian, environmental, or multifactorial. Sequencing currently performed for isolated sporadic OFCs; therefore, we estimated diagnostic yield 418 genes in 841 cases 294 controls.
The epilepsies are highly heritable conditions that commonly follow complex inheritance. While monogenic causes have been identified in rare familial epilepsies, most remain unsolved. We aimed to determine (1) whether common genetic variation contributes epilepsy risk, and (2) risk is enriched compared with non-familial (sporadic) epilepsies.Using variants derived from the largest genome-wide association study, we calculated polygenic scores (PRS) for patients (n = 1,818 1,181 families),...
Abstract Craniofacial development gives rise to the complex structures of face and involves interplay diverse cell types. Despite its importance, our understanding human-specific craniofacial developmental mechanisms their genetic underpinnings remains limited. Here, we present a comprehensive single-nucleus RNA sequencing (snRNA-seq) atlas human from tissues 24 embryos that span six key time points during embryonic period (4–8 post-conception weeks). This resource resolves transcriptional...
Orofacial clefts (OFCs) are the most common craniofacial birth defects, affecting 1 in 700 births, and have a strong genetic basis with high recurrence risk within families. While many of previous studies associated common, noncoding loci OFCs, on de novo variants (DNVs) OFC cases focused coding that could functional impact protein structure, contribution DNVs to formation OFCs has largely been ignored is not well understood. Therefore, we reanalyzed an existing dataset from 1,409 trios had...
Abstract De novo variants (DNs) are sporadically occurring that most commonly arise in the germline and present offspring but absent both parents. As they not under selective pressure, may be enriched for disease-causing alleles have been implicated multiple rare genetic disorders. Cleft palate (CP) is a common craniofacial congenital anomaly ∼1 1700 live births. Genome-wide association studies CP found fewer than dozen loci, while exome targeted sequencing family-based case-control cohorts...
Abstract In 1973, accidental contamination of Michigan livestock with polybrominated biphenyls (PBBs) led to the establishment a registry exposed individuals that have been followed for > 40 years. Besides being PBBs, this cohort has also polychlorinated (PCBs), structurally similar class environmental pollutants, at levels average US exposure. study, we examined association between current serum PCB and PBB various female reproductive health outcomes build upon previous work...
Summary Glycogen storage disease type IIIa (GSD IIIa) is an autosomal recessive caused by deficiency of glycogen debranching enzyme (GDE) in liver and muscle. The disorder clinically heterogeneous progressive, there no effective treatment. Previously a naturally occurring dog model for this condition was identified curly-coated retrievers (CCR). affected dogs carry frame-shift mutation the GDE gene have detectable activity We characterized detail expression progression eight from age 2 to 16...
Nonsyndromic orofacial clefts (OFCs) are a common birth defect and phenotypically heterogenous in the structure affected by cleft - lip (CL) palate (CLP) as well other features, such severity of cleft. Here, we focus on bilateral unilateral one dimension OFC severity, because genetic architecture these subtypes is not understood. We tested for subtype-specific associations 44 CL (BCL) cases, 434 (UCL) 530 CLP cases (BCLP), 1123 (UCLP) unrelated controls (N = 1626), using mixed-model...
Glycogen storage disease type Ia (GSD-Ia) is the inherited deficiency of glucose-6-phosphatase (G6Pase), primarily found in liver and kidney, which causes life-threatening hypoglycemia. Dogs with GSD-Ia were treated double-stranded adeno-associated virus (AAV) vectors encoding human G6Pase. Administration an AAV9 pseudotyped (AAV2/9) vector to seven consecutive neonates prevented hypoglycemia during fasting for up 8 hr; however, efficacy eventually waned between 2 30 months age,...
Abstract Orofacial clefts (OFCs) are common (1 in 700 births) congenital malformations that include a cleft lip (CL) and palate (CLP). These OFC subtypes also heterogeneous themselves, with the CL occurring on left, right, or both sides of upper lip. Unilateral CLP have 2:1 bias towards left‐sided clefts, suggesting nonrandom process. Here, we performed study left‐ right‐sided within to better understand genetic factors controlling laterality. We conducted genome‐wide modifier analyses by...
Exposure to polychlorinated biphenyls (PCBs), an endocrine-disrupting compound, is ubiquitous despite decades-old bans on the manufacture and use of PCBs. Increased exposure PCBs associated with adverse health consequences throughout life, including type 2 diabetes cancer. PCB also alterations in epigenetic marks gene transcription, which could lead outcomes, but many these are population-specific. To further investigate association between marks, DNA methylation was measured at 787,684 CpG...
Aim: Michigan residents were exposed to polybrominated biphenyls (PBBs) when it was accidentally added the food supply. Highly individuals report sex-specific health problems, but underlying biological mechanism behind these different risks is not known. Materials and methods: DNA methylation in blood from 381 women 277 men with PBB exposure analyzed MethylationEPIC BeadChip. Results: 675 CpGs associated PBBs levels males, while only 17 females (false discovery rate <0.05). No both sexes....
Advanced age increases risk for cancer, cardiovascular disease, and all-cause mortality.However, people do not at the same rate, biological (frequently measured through DNA methylation) can be older than chronological age.Environmental factors have been associated with rate of aging, but it is known whether persistent endocrine-disrupting compounds (EDCs) like polybrominated biphenyl (PBB) would associate acceleration.Three different epigenetic acceleration measures (intrinsic, extrinsic,...
Endocrine-disrupting compounds are associated with altered epigenetic regulation and adverse health outcomes, although inconsistent results suggest that people have varied responses to the same exposure. Interpersonal variation in response environmental exposures is not identified using standard, population-based methods. However, methods capture an individual's response, such as analyzing stochastic mutations (SEMs), may currently missed effects of To test whether polybrominated biphenyl...
Abstract As one of the most common structural birth defects, orofacial clefts (OFCs) have been studied for decades, and recent studies demonstrated that there are genetic differences between different phenotypic presentations OFCs. However, contribution rare variation genome-wide to subtypes OFCs has understudied, with focusing on or within targeted regions genome. Therefore, we used whole-genome sequencing data from Gabriella Miller Kids First Pediatric Research Program conduct a gene-based...
Cleft palate (CP) is one of the most common craniofacial birth defects; however, there are relatively few established genetic risk factors associated with its occurrence despite high heritability. Historically, CP has been studied as a single phenotype, although it manifests across spectrum defects involving hard and/or soft palate. We performed genome-wide association study using transmission disequilibrium tests 435 case-parent trios to evaluate broad risks for any cleft (ACP) (n = 435),...
Orofacial cleft (OFC) is a common human congenital anomaly. Epithelial-specific RNA splicing regulators ESRP1 and ESRP2 regulate craniofacial morphogenesis their disruption result in OFC zebrafish, mouse humans. Using esrp1/2 mutant zebrafish murine Py2T cell line models, we functionally tested the pathogenicity of ESRP1/2 gene variants. We found that many variants predicted by silico methods to be pathogenic were benign. Esrp1 also regulates alternative Ctnnd1 these genes are co-expressed...
Orofacial clefts (OFCs) are the most common craniofacial birth defects and often categorized into two etiologically distinct groups: cleft lip with or without palate (CL/P) isolated (CP). CP is highly heritable, but there still relatively few established genetic risk factors associated its occurrence compared to CL/P. Historically, has been studied as a single phenotype despite manifesting across spectrum of involving hard and/or soft palate. We performed GWAS using transmission...