A5054205591- Adipose Tissue and Metabolism
- Genetic Mapping and Diversity in Plants and Animals
- Genetic Associations and Epidemiology
- Genetic and phenotypic traits in livestock
- Nausea and vomiting management
- Peroxisome Proliferator-Activated Receptors
- RNA regulation and disease
- RNA Research and Splicing
- Epigenetics and DNA Methylation
- RNA and protein synthesis mechanisms
- RNA modifications and cancer
- Osteoarthritis Treatment and Mechanisms
- Metabolism, Diabetes, and Cancer
- Cellular transport and secretion
- E-commerce and Technology Innovations
- Pathogenesis and Treatment of Hiccups
- Ion channel regulation and function
- Zebrafish Biomedical Research Applications
- Asthma and respiratory diseases
- Cancer-related molecular mechanisms research
- CRISPR and Genetic Engineering
- Pancreatic function and diabetes
- Oral health in cancer treatment
- Aldose Reductase and Taurine
- Genomics and Rare Diseases
University School
2008-2024
Case Western Reserve University
2015-2024
Human Genome Sciences (United States)
2018
University of Michigan
2001-2013
Eisai (United States)
2011
Howard Hughes Medical Institute
2006
Hepatocellular carcinoma (HCC) is one of the leading causes cancer death worldwide, with ∼70% cases resulting from hepatitis B and C viral infections, aflatoxin exposure, chronic alcohol use or genetic liver diseases. The remaining ∼30% are associated obesity, type 2 diabetes related metabolic diseases, although a direct link between these pathologies HCCs has not been established. We tested long-term effects high-fat low-fat diets on males two inbred strains mice discovered that C57BL/6J...
The severity of many inherited disorders is influenced by genetic background. We describe a modifier interaction in C57BL/6Jmice that converts chronic movement disorder into lethal neurological disease. primary mutation (medJ) changes splice donor site the sodium channel gene Scn8a (Nav1.6). characteristic strain C57BL/6Jand introduces nonsense codon 1 (SCNM1), zinc finger protein and putative factor. An internally deleted SCNM1 also predicted as result exon skipping associated with...
Thrombospondin 1 (THBS1 or TSP-1) is a circulating glycoprotein highly expressed in hypertrophic visceral adipose tissues of humans and mice. High-fat diet (HFD) feeding induces the robust increase THBS1 early stages HFD challenge. The loss Thbs1 protects male mice from diet-induced weight gain adipocyte hypertrophy. Hyperinsulinemic euglycemic clamp study has demonstrated that Thbs1-null are protected HFD-induced insulin resistance. Tissue-specific glucose uptake revealed insulin-sensitive...
Cytokinetic membrane abscission is a spatially and temporally regulated process that requires ESCRT (endosomal sorting complexes required for transport)–dependent control of remodeling at the midbody, subcellular organelle defines cleavage site. Alteration function can lead to cataract, but underlying mechanism its relation cytokinesis are unclear. We found lens-specific cytokinetic PI3K-C2α (phosphatidylinositol-4-phosphate 3-kinase catalytic subunit type 2α), lipid product PI(3,4)P
The zebrafish is a powerful model for studying vascular development, demonstrating remarkable conservation of this process with mammals. Here, we identify mutant, redhead ( rhd mi149 ), that exhibits embryonic CNS hemorrhage intact gross development the vasculature and normal hemostatic function. We show phenotype caused by hypomorphic mutation in p21-activated kinase 2a pak2a ). PAK2 acts downstream Rho-family GTPases CDC42 RAC has been implicated angiogenesis, regulation cytoskeletal...
Current treatments have largely failed to slow the rapidly increasing world-wide prevalence of obesity and its co-morbidities. Despite a strong genetic contribution (40–70%), only small percentage heritability is explained with current knowledge monogenic abnormalities, common sequence variants conventional modes inheritance. Epigenetic effects are rarely tested in humans because difficulties arranging studies that distinguish transgenerational inheritance while simultaneously controlling...
Abstract Background Somatic mutations in the ubiquitin-specific peptidase 8 (USP8) gene are common corticotropinomas of children with Cushing disease (CD). We report a unique patient germline USP8 mutation who presented CD and constellation other findings that constitute an intriguing genetic syndrome. Case Description describe 16-year-old female CD, developmental delay, dysmorphic features, ichthyosiform hyperkeratosis, chronic lung disease, kidney hyperglycemia, dilated cardiomyopathy...
Primary ovarian insufficiency (POI) is characterized by amenorrhea and loss or dysfunction of follicles prior to the age 40. POI has been associated with autosomal recessive mutations in genes involving hormonal signaling folliculogenesis, however, genetic etiology most often remains unknown. Here we report MRPS22 homozygous missense variants c.404G>A (p.R135Q) c.605G>A (p.R202H) identified four females from two independent consanguineous families as a novel cause adolescents. Both are rare,...
PIK3C2A is a class II member of the phosphoinositide 3-kinase (PI3K) family that catalyzes phosphorylation phosphatidylinositol (PI) into PI(3)P and PI(4)P PI(3,4)P2. At cellular level, critical for formation cilia receptor mediated endocytosis, among other biological functions. We identified homozygous loss-of-function mutations in children from three independent consanguineous families with short stature, coarse facial features, cataracts secondary glaucoma, multiple skeletal...
Although central to many studies of phenotypic variation and disease susceptibility, characterizing the genetic architecture complex traits has been unexpectedly difficult. For example, most susceptibility genes that contribute highly heritable conditions such as obesity type 2 diabetes (T2D) remain be identified despite intensive study. We took advantage mouse models diet-induced metabolic in chromosome substitution strains (CSSs) both characterize glucose homeostasis test feasibility gene...
Epidemiological and animal studies have shown that maternal diet can influence metabolism in adult offspring. However, the molecular mechanisms underlying these changes remain poorly understood. Here, we characterize phenotypes induced by obesity a mouse model examine gene expression epigenetic offspring.We analyzed genetically identical male mice born from dams fed high- or low-fat throughout pregnancy until day 21 postpartum. After weaning, half of males each group were high-fat diet,...
Abstract Long non-coding RNAs (lncRNAs) are frequently dysregulated in many human cancers. We sought to identify candidate oncogenic lncRNAs colon tumors by utilizing RNA sequencing data from 22 and adjacent normal samples The Cancer Genome Atlas (TCGA). analysis led the identification of ~200 differentially expressed lncRNAs. Validation an independent cohort patient-derived cancer cell lines identified a novel lncRNA, lincDUSP, as potential oncogene. Knockdown lincDUSP tumor resulted...
Osteoarthritis (OA) is the most prevalent joint disorder, causing pain and disability predominantly in aging population but also affecting young individuals. Current treatments are limited to use of anti-inflammatory drugs alleviate symptoms or degenerated replacement by a prosthetic implant at end stage disease. We hypothesized that degenerative cartilage defects can be treated using nasal chondrocyte–based tissue-engineered (N-TEC). demonstrate N-TEC maintained cartilaginous properties...
Obesity is the result of excess energy intake relative to expenditure, however little known about why some individuals are more prone weight gain than others. Inbred strains mice also vary in their susceptibility obesity and therefore represent a valuable model study genetics physiology its co-morbidities such as type 2 diabetes. C57BL/6J susceptible insulin resistance when fed an obesogenic diet, whereas A/J resistant despite increased caloric intake. Analysis B6- A/J-derived chromosome...
The breakdown of stored fat deposits into its components is a highly regulated process that maintains plasma levels free fatty acids to supply energy cells. Insulin-mediated transcription Atgl, the enzyme mediates rate-limiting step in lipolysis, key point this regulation. Under conditions such as obesity or insulin resistance, Atgl often misregulated, which can contribute overall disease progression. mechanisms by induced during adipogenesis are not fully understood. We utilized...
The inability of cells to adapt increased environmental tonicity can lead inflammatory gene expression and pathogenesis. Rel family transcription factors TonEBP NF-κB p65 play critical roles in the switch from osmoadaptive homeostasis inflammation, respectively. Here we identified PACT-mediated PKR kinase activation as a marker termination adaptation initiation inflammation Mus musculus embryonic fibroblasts. We found that high stress-induced PACT-PKR inhibits interaction between c-Rel...
Eukaryotic initiation factor 2A (eIF2A) is a 65 kDa protein that functions in minor pathways, which affect the translation of only subset messenger ribonucleic acid (mRNAs), such as internal ribosome entry site (IRES)-containing mRNAs and/or harboring upstream near cognate/non-AUG start codons. These non-canonical events are important for regulation synthesis during cellular development integrated stress response. Selective eIF2A knockdown systems significantly inhibits mRNAs, rely on...
The ENU-induced neurological mutant ataxia3 was mapped to distal mouse chromosome 15. Sequencing of the positional candidate gene Scn8a encoding sodium channel Na v 1.6 identified a T>C transition in exon 1 resulting amino acid substitution p.S21P near N terminus channel. cytoplasmic N-terminal region is evolutionarily conserved but its function has not been well characterized. homozygotes exhibit severe disorder that includes ataxia, tremor, and juvenile lethality. Unlike null mice, they...