A5023379825- Cellular transport and secretion
- Genomics and Rare Diseases
- Lysosomal Storage Disorders Research
- Biomedical Research and Pathophysiology
- Genetic and Kidney Cyst Diseases
- Renal and related cancers
- Immunodeficiency and Autoimmune Disorders
- Epigenetics and DNA Methylation
- Pancreatic function and diabetes
- RNA Research and Splicing
- Cancer Mechanisms and Therapy
- Urinary and Genital Oncology Studies
- Chromatin Remodeling and Cancer
- Cerebrovascular and genetic disorders
- Neurological diseases and metabolism
- RNA modifications and cancer
- Genomic variations and chromosomal abnormalities
- Abdominal Trauma and Injuries
- Hepatitis B Virus Studies
- Renal Diseases and Glomerulopathies
- Chromosomal and Genetic Variations
- Esophageal and GI Pathology
- Bladder and Urothelial Cancer Treatments
- Cancer Treatment and Pharmacology
- Congenital heart defects research
Nationwide Children's Hospital
2022-2025
Purdue University West Lafayette
2015-2023
Center for Cancer Research
2019
Metabolism and Renal Physiology
2014
Brigham and Women's Hospital
2013
Harvard University
2013
Currently, no blood biomarker that specifically indicates injury to the proximal tubule of kidney has been identified. Kidney molecule-1 (KIM-1) is highly upregulated in tubular cells following injury. The ectodomain KIM-1 shed into lumen, and serves as a urinary We report also Sensitive assays measure plasma serum mice, rats, humans were developed validated current study. Plasma levels increased with increasing periods ischemia (10, 20, or 30 minutes) early 3 hours after reperfusion;...
Abstract Variants in the AUTS2 gene are associated with a broad spectrum of neurological conditions characterized by intellectual disability, microcephaly, and congenital brain malformations. Here, we use human cerebral organoid model to investigate pathophysiology heterozygous de novo missense variant identified patient multiple impairments including primary microcephaly profound disability. Proband organoids exhibit reduced growth, deficits neural progenitor cell (NPC) proliferation...
ABSTRACT Pathogenic variants in GNAS can cause a wide range of diseases including pseudohypoparathyroidism, pseudopseudohypoparathyroidism, McCune‐Albright syndrome, among others. The specific phenotypic features that may be seen are influenced by the variant type and location gene, whether it causes loss or gain function, is germline somatic nature. locus imprinted, which also results parent‐of‐origin effect. Typically, function on maternal allele associated with variable hormonal...
Abstract Background. Renal cell carcinoma (RCC) is characterized by lack of early warning signs, diverse clinical manifestations, absence a reliable diagnostic and predictive biomarker, resistance to targeted therapy. Thus, novel approaches for diagnosis, management treatment RCC are urgently needed. Kidney Injury Molecule-1 (KIM-1) not expressed in normal kidney tissues but markedly up-regulated dedifferentiated proximal tubular epithelial cells following renal injury. We demonstrated that...
Bladder cancer is the sixth most common in United States, and it exhibits an alarming 70% recurrence rate. Thus, development of more efficient antibladder approaches a high priority. Accordingly, this work provides basis for transformative anticancer strategy that takes advantage unique characteristics bladder. Unlike mucin-shielded normal bladder cells, cells are exposed to lumen overexpress EGFR. Therefore, we used EGF-conjugated anthrax toxin after targeting EGFR was internalized...
Abstract Lowe Syndrome (LS) is a lethal genetic disorder caused by mutations in the OCRL1 gene which encodes lipid 5′ phosphatase Ocrl1. Patients exhibit characteristic triad of symptoms including eye, brain and kidney abnormalities with renal failure as most common cause premature death. Over 200 have been identified LS, but their specific impact on cellular processes unknown. Despite observations heterogeneity patient symptom severity, there little understanding correlation between...
Lowe syndrome is an X-linked condition characterized by congenital cataracts, neurological abnormalities and kidney malfunction. This lethal disease caused mutations in the OCRL1 gene, which encodes for phosphatidylinositol 5-phosphatase Ocrl1. While past decade we witnessed substantial progress identification characterization of LS patient cellular phenotypes, many these studies have been performed knocked-down cell lines or patient's cells from accessible types such as skin fibroblasts,...
Lowe Syndrome (LS) is a condition due to mutations in the OCRL1 gene, characterized by congenital cataracts, intellectual disability, and kidney malfunction. Unfortunately, patients succumb renal failure after adolescence. This study centered investigating biochemical phenotypic impact of patient's variants (OCRL1VAR). Specifically, we tested hypothesis that some OCRL1VAR are stabilized non-functional conformation focusing on missense affecting phosphatase domain, but not changing residues...
Lowe syndrome (LS) is an X-linked developmental disease characterized by cognitive deficiencies, bilateral congenital cataracts and renal dysfunction. Unfortunately, this leads to the early death of affected children often due kidney failure. Although condition was first described in 1950s gene (OCRL1) identified 1990s, its pathophysiological mechanism not fully understood there no LS-specific cure available patients. Here we report two important signaling pathways LS patient cells. While...
Abstract Somatic alterations in the fibroblast growth factor receptor (FGFR) gene family (FGFR1/2/3) have been implicated tumorigenesis across pediatric low-grade glioneuronal neoplasms and represent a potential therapeutic target. FGFR rearrangements internal tandem duplication (ITD) cause constitutive tyrosine kinase activation, thereby promoting tumor cell growth, differentiation, survival through complex downstream signaling, including via mitogen activated protein (MAPK) pathway. With...
Long-read sequencing can often overcome the deficiencies in routine microarray or short-read technologies detecting complex genomic rearrangements. Here we used Pacific Biosciences circular consensus to resolve rearrangements two patients with rare genetic anomalies. Copy number variants (CNVs) identified by clinical —chr8p deletion and chr8q duplication patient 1, interstitial deletions of chr18q 2—were suggestive underlying genome not only confirmed these CNVs but also revealed their...
Background: Leigh syndrome is a rare, genetic, and severe mitochondrial disorder characterized by neuromuscular issues (ataxia, seizure, hypotonia, developmental delay, dystonia) ocular abnormalities (nystagmus, atrophy, strabismus, ptosis). It caused pathogenic variants in either or nuclear DNA genes, with an estimated incidence rate of 1 per 40,000 live births. Case presentation: Herein, we present infant male nystagmus, delay who carried clinical diagnosis Leigh-like syndrome. Cerebral...
There are currently over 7,000 rare diseases estimated to affect nearly 30 million Americans, according the National Organization for Rare Disease (NORD). A variety of genetic, biochemical, and other diagnostic tests available such patients. While microarrays gene panels often considered standard care, clinicians increasingly ordering exome sequencing on patients as a first-tier assay. Large cohort studies have shown that has consistent yield 30-50% depending patient's condition, but this...
Common variable immune deficiency (CVID) is a heterogenous group of disorders characterized by varying degrees hypogammaglobulinemia, recurrent infections, and autoimmunity. Currently, pathogenic variants are identified in approximately 20-30% CVID cases. Here we report 3-generation family with autosomal dominant Variable Immunodeficiency diagnosed 9 affected individuals. Although primary panels exome sequencing were non-diagnostic, whole genome revealed novel, c.499C > T: p.His167Tyr...
De novo variants in CSNK2A1 cause autosomal dominant Okur-Chung neurodevelopmental syndrome (OCNDS). OCNDS has an evolving clinical phenotype predominantly characterized by intellectual disability, global delays, dysmorphic features, and immunological manifestations. Microcephaly, defined as a small head circumference, is not widely recognized classical presentation. Here, we describe four individuals from three unrelated families who shared several features characteristic of underlying...
ABSTRACT Variants in the AUTS2 gene are associated with a broad spectrum of neurological conditions characterized by intellectual disability, microcephaly, and congenital brain malformations. Here, we use human cerebral organoid (CO) model to investigate pathophysiology heterozygous de novo missense variant identified patient multiple impairments including primary microcephaly profound disability. Proband COs exhibit reduced growth, deficits neural progenitor cell (NPC) proliferation...
Noncoding and synonymous coding variants that exert their effects via alternative splicing are increasingly recognized as an important category of disease-causing variants. In this report, we describe two siblings who presented with hypotonia, profound developmental delays, seizures. Brain magnetic resonance imaging (MRI) in the proband at 5 yr showed diffuse cerebral cerebellar white matter volume loss. Both later developed ventilator-dependent respiratory insufficiency scoliosis currently...
OPINION article Front. Cell Dev. Biol., 28 April 2022Sec. Membrane Traffic https://doi.org/10.3389/fcell.2022.886448
Anorectal malformations (ARM) constitute a group of congenital defects the gastrointestinal and urogenital systems. They affect males females, with an estimated worldwide prevalence 1 in 5,000 live births. These are clinically heterogeneous can be part syndromic presentation (Syndromic ARM) or as non-syndromic entity (Non-syndromic ARM). Despite well-recognized heritability ARM, genetic etiology most patients is unknown. In this study, we describe three siblings diverse anomalies...