A5016479884- Pancreatic function and diabetes
- Neuroendocrine Tumor Research Advances
- Diabetes and associated disorders
- Genomic variations and chromosomal abnormalities
- Neuroblastoma Research and Treatments
- Advanced Breast Cancer Therapies
- Congenital heart defects research
- Neurofibromatosis and Schwannoma Cases
- Prenatal Screening and Diagnostics
- Genomics and Rare Diseases
- Receptor Mechanisms and Signaling
- Fibroblast Growth Factor Research
- Cancer Genomics and Diagnostics
- Congenital Heart Disease Studies
- Down syndrome and intellectual disability research
- Tracheal and airway disorders
- Hedgehog Signaling Pathway Studies
- Protein Degradation and Inhibitors
- Religion, Society, and Development
- Congenital Ear and Nasal Anomalies
- Pancreatic and Hepatic Oncology Research
- Lung Cancer Research Studies
- Williams Syndrome Research
- Ocular Oncology and Treatments
- Medical History and Innovations
University of Iowa Health Care
2024
University of Iowa
1999-2023
University of Iowa Hospitals and Clinics
2002-2022
Malignant peripheral nerve sheath tumors (MPNST) are deadly sarcomas that lack effective therapies. In most MPNSTs, the retinoblastoma (RB1) tumor suppressor is disabled by hyperactivation of cyclin-dependent kinases (CDK), commonly through loss CDK-inhibitory proteins such as p27(Kip1). RABL6A an inhibitor RB1 whose role in MPNSTs unknown. To gain insight into MPNST development and establish new treatment options, we investigated RABL6A-RB1 signaling CDK inhibitor-based therapy MPNSTs.We...
Abstract Microdeletions of the long arm chromosome 17 are being reported with increasing frequency. Deletions 17q22q23.2 may represent a genetically recognizable phenotype although its spectrum genomic abnormalities, clinical manifestations, and critical regions not fully delineated. Isolated reports small case series suggest that deletions result in haploinsufficiency dosage sensitive genes NOG , TBX2 TBX4 which be responsible for many aspects phenotype. Shared features this group patients...
Mechanisms of neuroendocrine tumor (NET) proliferation are poorly understood, and therapies that effectively control NET progression metastatic disease limited. We found amplification a putative oncogene, RABL6A, in primary human pancreatic NETs (PNET) correlated with high-level RABL6A protein expression. Consistent those results, stable silencing cultured BON-1 PNET cells revealed it is essential for their survival. Cells lacking predominantly arrested G1 phase moderate mitotic block....
Abstract Turner syndrome (TS) is a chromosomal disorder caused by complete or partial loss of the second sex chromosome and exhibits phenotypic heterogeneity, even after accounting for mosaicism karyotypic variation. Congenital heart defects (CHD) are found in up to 45 percent girls with TS span continuum obstructive left-sided lesions, bicuspid aortic valve (BAV) being most common. Several recent studies have demonstrated genome-wide impact X haploinsufficiency, including global...
Functional copy number alterations (fCNAs) are DNA changes with concordant differential gene expression. These less likely to be bystander genetic lesions and could serve as robust reproducible tumor biomarkers. To identify candidate fCNAs in neuroendocrine tumors (NETs), we integrated chromosomal microarray (CMA) RNA-seq expression data from 31 pancreatic (pNET) 33 small bowel (sbNET). Tumors were resected 47 early disease progression (24 months) patients. Candidate that accurately...
Hypothalamic hamartoma with gelastic seizures is a well-established cause of drug-resistant epilepsy in early life. The development novel surgical techniques has permitted the genomic interrogation hypothalamic tissue. This revealed causative mosaic variants within GLI3, OFD1 and other key regulators sonic-hedgehog pathway minority cases. Sonic-hedgehog signalling proteins localize to cellular organelle primary cilia. We therefore explored hypothesis that cilia gene may underlie hitherto...
Functional copy-number alterations (fCNAs) are DNA changes with concordant differential gene expression. These less likely to be bystander genetic lesions and could serve as robust reproducible tumor biomarkers. To identify candidate fCNAs in neuroendocrine tumors (NETs), we integrated chromosomal microarray (CMA) RNA-seq gene-expression data from 31 pancreatic (pNETs) 33 small-bowel (sbNETs). Tumors were resected 47 early-disease-progression (<24 months) 17 late-disease-progression...
The 22q11.2 deletion syndrome (22q11.2DS) is the most common contiguous microdeletion affecting humans and exhibits extreme phenotypic heterogeneity. Patients can manifest any combination of comorbidities including congenital heart disease, hypoparathyroidism, cleft palate, kidney abnormalities, neurodevelopmental disorders, immune dysfunction. Immunodeficiency present in majority patients with 22q11.2DS second leading cause death these patients. Knowing genetic determinants dysfunction will...
An infant is reported who presented with a de novo 21;21 translocation trisomy 21 and an atypical phenotype for Down syndrome (DS). Findings included microcephaly, small stature, downslanting palpebral fissures, absent Brushfield spots, moderate micrognathia, left ptosis, torticollis, severe developmental delay, seizures, hypertonia. Further clinical evaluation using both the diagnostic criteria DS Jackson checklist of 25 signs was inconsistent diagnosis DS. Blood karyotype revealed:...
An infant is reported who presented with a de novo 21;21 translocation trisomy 21 and an atypical phenotype for Down syndrome (DS). Findings included microcephaly, small stature, downslanting palpebral fissures, absent Brushfield spots, moderate micrognathia, left ptosis, torticollis, severe developmental delay, seizures, hypertonia. Further clinical evaluation using both the diagnostic criteria DS Jackson checklist of 25 signs was inconsistent diagnosis DS. Blood karyotype revealed: 46,...
Abstract The interpretation of clinical chromosomal microarrays (CMAs) has historically relied on the relevance identified copy number variants (CNVs) to phenotype. New guidelines are focused standardizing pathogenicity classifications based genomic location, gene content, and previous publications, rather than immediate relevance. Here we report DISCRIMINATOR, which was developed assign provisional location by integrating information putative benign pathogenic loci in human genome. However,...
Abstract While copy number variants (CNVs) have been identified as an important cause of rare genetic disorders, they also in unaffected control populations, making clinical interpretation these lesions challenging. Discriminating benign CNVs from those pathogenic for therefore, relies on understanding what regions the human genome are tolerant to variation. Benign-Ex is a python-based program that uses information databases generate one or more interval map(s) and then identifies optimal...
<p>Table S1. List of differentially regulated genes caused by RABL6A knockdown (KD), relative to control (CON), in BON-1 PNET cells.</p>
<p>Figure S6. Down-regulation of p27 in arrested RABL6A knockdown cells promotes S phase entry.</p>
<p>Figure S2. Representative IPA mechanistic network for signaling regulators predicted to contribute the RABL6A knockdown phenotype.</p>
<p>Figure S3. Quantitative RT-PCR showing RABL6A depletion does not affect p21 mRNA expression</p>
<p>Figure S5. Effect of RABL6A overexpression on Rb1 and p21 mRNA protein expression</p>
<p>Figure S1. Quantitative PCR measurement of human RABL6A DNA copy number in PNET patient samples.</p>