A5013622096- Regulation of Appetite and Obesity
- Genetic and Kidney Cyst Diseases
- Renal and related cancers
- Hypothalamic control of reproductive hormones
- Adipokines, Inflammation, and Metabolic Diseases
- Adipose Tissue and Metabolism
- Ear Surgery and Otitis Media
- Neuroendocrine regulation and behavior
- Biochemical Analysis and Sensing Techniques
- Genetic Syndromes and Imprinting
- Hearing, Cochlea, Tinnitus, Genetics
- Metabolism and Genetic Disorders
- Ovarian function and disorders
- Mitochondrial Function and Pathology
- Renal Diseases and Glomerulopathies
- Protist diversity and phylogeny
- Hedgehog Signaling Pathway Studies
- Hair Growth and Disorders
- Nasal Surgery and Airway Studies
- Kruppel-like factors research
- Fetal and Pediatric Neurological Disorders
- Metalloenzymes and iron-sulfur proteins
- Estrogen and related hormone effects
- Genomic variations and chromosomal abnormalities
- Coenzyme Q10 studies and effects
University of Michigan–Ann Arbor
2013-2024
Diabetes Australia
2024
ORCID
2024
Laboratoire d’immunologie intégrative du cancer
2020
Universidade Estadual de Campinas (UNICAMP)
2016
Texas Tech University Health Sciences Center
2014
Texas Tech University
2014
Michigan Medicine
2013
Ann Arbor Center for Independent Living
2010
Michigan United
2009
Identification of single-gene causes steroid-resistant nephrotic syndrome (SRNS) has furthered the understanding pathogenesis this disease. Here, using a combination homozygosity mapping and whole human exome resequencing, we identified mutations in aarF domain containing kinase 4 (ADCK4) gene 15 individuals with SRNS from 8 unrelated families. ADCK4 was highly similar to ADCK3, which been shown participate coenzyme Q10 (CoQ10) biosynthesis. Mutations resulted reduced CoQ10 levels...
The identification of recessive disease-causing genes by homozygosity mapping is often restricted lack suitable consanguineous families. To overcome these limitations, we apply to single affected individuals from outbred populations. In 72 54 kindred ascertained worldwide with known homozygous mutations in 13 different disease genes, performed total genome using 250,000 SNP arrays. Likelihood ratio Z-scores (ZLR) were plotted across the detect ZLR peaks that reflect segments descent, which...
<h3>Objective</h3> To identify disease-causing mutations within coding regions of 11 known NPHP genes (<i>NPHP1-NPHP11</i>) in a cohort 192 patients diagnosed with nephronophthisis-associated ciliopathy, at low cost. <h3>Methods</h3> Mutation analysis was carried out using PCR-based 48.48 Access Array microfluidic technology (Fluidigm) consecutive next-generation sequencing. We applied 10-fold primer multiplexing approach allowing amplification 475 amplicons (251 exons) for 48 DNA samples...
The autosomal recessive kidney disease nephronophthisis (NPHP) constitutes the most frequent genetic cause of terminal renal failure in first 3 decades life. Ten causative genes (NPHP1-NPHP9 and NPHP11), whose products localize to primary cilia-centrosome complex, support unifying concept that cystic diseases are "ciliopathies". Using genome-wide homozygosity mapping, we report here what believe be a new locus (NPHP-like 1 [NPHPL1]) for an NPHP-like nephropathy. In 2 families with phenotype,...
Nephronophthisis (NPHP), an autosomal recessive kidney disease, is the most frequent genetic cause of chronic renal failure in first three decades life. Mutations eight genes (NPHP1-8) have been identified. We here describe a combined approach for mutation screening NPHP1, NPHP2, NPHP3, NPHP4, and NPHP5 worldwide cohort 470 unrelated patients with NPHP. First, homozygous NPHP1 deletions were detected 97 (21%) by multiplex PCR. Second, 25 infantile NPHP screened mutations inversin...
The hypothalamic ventral premammillary nucleus (PMv) is a glutamatergic essential for the metabolic control of reproduction. However, conditional deletion leptin receptor long form (LepRb) in vesicular glutamate transporter 2 (Vglut2) expressing neurons results virtually no reproductive deficits. In this study, we determined role neurotransmission from responsive PMv on puberty and fertility. We first assessed if stimulation induces luteinizing hormone (LH) release fed adult females. used...
Obese women are at high risk of pregnancy complications, including preeclampsia, miscarriage, preterm birth, stillbirth, and neonatal death. In the current study, we aimed to determine effects obesity on outcome placental gene expression in preclinical mouse models genetic nutritional obesity. The leptin receptor (LepR) null-reactivatable (LepRloxTB), LepR-deficient (Leprdb/+), high-fat diet (HFD)–fed mice were assessed for fertility, outcome, morphology, transcriptome using standard...
The role of PI3K in leptin physiology has been difficult to determine due its actions downstream several metabolic cues, including insulin. Here, we used a series mouse models dissociate the roles specific catalytic subunits and insulin receptor (InsR) signaling. We show that disruption p110α p110β cells (LRΔα+β) produces lean phenotype associated with increased energy expenditure, locomotor activity, thermogenesis. LRΔα+β mice have deficient growth delayed puberty. Single subunit deletion...
A temporary and reversible inhibition of the hypothalamo-pituitary-gonadal axis is adaptive when energy reserves are diminished, allowing individual survival accumulation for eventual reproduction. The AMP-activated protein kinase (AMPK) works as a cellular sensor AMP to ATP ratio ultimately availability. Activation AMPK suppresses ATP-consuming processes stimulates ATP-producing pathways. α2 catalytic subunit expressed in multiple hypothalamic nuclei including those associated with...
Epidemiological and genome-wide association studies (GWAS) have shown high correlation between childhood obesity advance in puberty. Early age at menarche is associated with a series of morbidities, including breast cancer, cardiovascular diseases, type 2 diabetes, obesity. The adipocyte hormone leptin signals the amount fat stores to neuroendocrine reproductive axis via direct actions brain. Using mouse genetics, we others identified hypothalamic ventral premammillary nucleus (PMv)...
Leptin signals energy sufficiency to the reproductive hypothalamic-pituitary-gonadal (HPG) axis. Studies using genetic models have demonstrated that hypothalamic neurons are major players mediating these effects. receptor (LepR) is also expressed in pituitary gland and gonads, but physiological effects of leptin sites still unclear. Female mice with selective deletion LepR a subset gonadotropes show normal pubertal development impaired fertility. Conditional approaches, however, often result...