A5024024970- Retinal Development and Disorders
- Genetic and Kidney Cyst Diseases
- Congenital heart defects research
- RNA modifications and cancer
- Cellular transport and secretion
- Congenital Ear and Nasal Anomalies
- Olfactory and Sensory Function Studies
- Genetic Syndromes and Imprinting
- Photoreceptor and optogenetics research
- Zebrafish Biomedical Research Applications
- Renal and related cancers
- Protist diversity and phylogeny
- Genomic variations and chromosomal abnormalities
- Genetics and Neurodevelopmental Disorders
- Biochemical Analysis and Sensing Techniques
- Neurobiology and Insect Physiology Research
- Hedgehog Signaling Pathway Studies
- RNA and protein synthesis mechanisms
- Microtubule and mitosis dynamics
- RNA regulation and disease
- Pregnancy and preeclampsia studies
- Mitochondrial Function and Pathology
- Immune responses and vaccinations
- IL-33, ST2, and ILC Pathways
- Inflammatory Bowel Disease
Duke University Hospital
2011-2024
Duke Medical Center
2011-2024
University of Michigan
2019-2023
Michigan United
2019-2021
Duke University
2011-2017
University of Louisville
2008-2015
Institute for Disease Modeling
2013
University of Wisconsin–Madison
2009
Institute of Virology of the Slovak Academy of Sciences
1987
Abstract Cellular organelles provide opportunities to relate biological mechanisms disease. Here we use affinity proteomics, genetics and cell biology interrogate cilia: poorly understood organelles, where defects cause genetic diseases. Two hundred seventeen tagged human ciliary proteins create a final landscape of 1,319 proteins, 4,905 interactions 52 complexes. Reverse tagging, repetition purifications statistical analyses, produce high-resolution network that reveals organelle-specific...
Charcot-Marie-Tooth (CMT) disease is a clinically and genetically heterogeneous distal symmetric polyneuropathy. Whole-exome sequencing (WES) of 40 individuals from 37 unrelated families with CMT-like peripheral neuropathy refractory to molecular diagnosis identified apparent causal mutations in ∼45% (17/37) families. Three candidate genes are proposed, supported by combination genetic vivo studies. Aggregate analysis mutation data revealed significantly increased number rare variants across...
Humans use a family of more than 400 olfactory receptors (ORs) to detect odors, but there is currently no model that can predict perception from receptor activity patterns. Genetic variation in human ORs abundant and alters function, allowing us examine the relationship between function perception. We sequenced OR repertoire 332 individuals examined how genetic affected 276 phenotypes, including perceived intensity pleasantness 68 odorants at two concentrations, detection thresholds three...
Significance Inflammatory bowel diseases (IBD), including Crohn’s disease and ulcerative colitis, are intestinal disorders of poorly understood origin associated with significant morbidity mortality. A crucial factor IBD onset is the presence elevated levels proinflammatory cytokine tumor necrosis (TNF) in intestine, signified by use anti-TNF therapy to treat patients disease. Despite its pathogenic relevance, mechanisms regulating TNF expression remain largely unknown. Here, we show that...
Abstract Neurodevelopmental defects in humans represent a clinically heterogeneous group of disorders. Here, we report the genetic and functional dissection multigenerational pedigree with an X-linked syndromic disorder hallmarked by microcephaly, growth retardation, seizures. Using intellectual disability (XLID) next-generation sequencing diagnostic panel, identified novel missense mutation gene encoding 60S ribosomal protein L10 (RPL10), locus associated previously autism spectrum...
The glaucomas comprise a genetically complex group of retinal neuropathies that typically occur late in life and are characterized by progressive pathology the optic nerve head degeneration ganglion cells. In addition to age family history, other significant risk factors for glaucoma include elevated intraocular pressure (IOP) myopia. complexity has made it difficult model animals, but also challenging identify responsible genes. We have used zebrafish complex, recessive mutant shows...
T2-family acidic endoribonucleases are represented in all genomes. A physiological role for RNase T2 has yet to be defined metazoa. RNASET2 mutation humans is linked with a leukoencephalopathy that arises infancy characterized by cortical cysts and multifocal white matter lesions. We now show localization of within lysosomes. Further, we demonstrate loss rnaset2 mutant zebrafish results accumulation undigested rRNA lysosomes neurons the brain. using high field intensity magnetic resonance...
Significance Inactivating mutations in the chromodomain helicase DNA binding protein 7 ( CHD7 ) gene causes a severe developmental disorder known as CHARGE syndrome. Recently, several missense have been reported isolated gonadotropin-releasing hormone (GnRH) -deficiency (IGD) patients who lack full features. However, precise functional consequence of these IGD-associated on activity is not known. This study confirms predominance alleles 5% IGD and provides, to our knowledge, first...
Amyotrophic lateral sclerosis [1] is a genetically heterogeneous neurodegenerative disorder, characterized by late-onset degeneration of motor neurons leading to progressive limb and bulbar weakness, as well the respiratory muscles, which primary cause disease fatality. To date, over 25 genes have been implicated causative in ALS with C9orf72, SOD1, FUS, TARDBP accounting for majority positive cases. We identified two patients Italian French ancestry clinical diagnosis juvenile-onset who...
Forward genetic approaches in zebrafish have provided invaluable information about developmental processes. However, the relative difficulty of mapping and isolating mutations has limited number new screens. Recent improvements annotation genome coupled to a reduction sequencing costs prompted development whole RNA for gene discovery. Here we describe exome (WES) approach that allows rapid cost-effective identification mutations. We used our WES methodology isolate four cause kidney cysts;...
The first critical stage in salamander or teleost appendage regeneration is creation of a specialized epidermis that instructs growth from underlying stump tissue. Here, we performed forward genetic screen for mutations impair this process amputated zebrafish fins. Positional cloning and complementation assays identified temperature-sensitive allele the ECM component laminin beta 1a (lamb1a) blocks fin regeneration. lamb1a, but not its paralog lamb1b, sharply induced subset epithelial cells...
Abstract Low‐density lipoprotein receptor‐related protein 2 (LRP2) is a multifunctional cell surface receptor conserved from nematodes to humans. In mammals, it acts as regulator of sonic hedgehog and bone morphogenetic pathways in patterning the embryonic forebrain clearance adult kidney. Little known about activities this LRP other phyla. Here, we extend functional elucidation LRP2 zebrafish model organism (dys)function. We demonstrate that expression Lrp2 larval fish recapitulates...
Analyzing the molecular architecture of native multiprotein complexes via biochemical methods has so far been difficult and error prone. Protein complex isolation by affinity purification can define protein repertoire a given complex, yet, it remains to gain knowledge its substructure or modular composition. Here, we introduce SDS concentration gradient induced decomposition coupled quantitative mass spectrometry in silico elution profile distance analysis. By applying this new method...
Abstract Hermansky-Pudlak Syndrome (HPS) is a set of genetically heterogeneous diseases caused by mutations in one nine known HPS genes. patients display oculocutaneous hypopigmentation and bleeding diathesis and, depending on the disease subtype, pulmonary fibrosis, congenital nystagmus, reduced visual acuity, platelet aggregation deficiency. Mouse models for all subtypes have contributed greatly to our understanding disease, but many molecular cellular mechanisms underlying remain unknown....
Mutations at some retinitis pigmentosa (RP) loci are associated with variable penetrance and expressivity, exacerbating diagnostic challenges. The purpose of this study was to dissect the genetic underpinnings nonsyndromic RP age onset in a large Mexican family.We ascertained members large, multigenerational pedigree using complete ophthalmic examination. We performed whole exome sequencing on two affected first cousins, an obligate carrier, married-in spouse. Confirmatory candidate variants...