A5021354665- Neonatal Respiratory Health Research
- Congenital Diaphragmatic Hernia Studies
- Salivary Gland Disorders and Functions
- Carcinogens and Genotoxicity Assessment
- bioluminescence and chemiluminescence research
- 3D Printing in Biomedical Research
- Effects of Radiation Exposure
- DNA Repair Mechanisms
- Respiratory viral infections research
- Proteoglycans and glycosaminoglycans research
- Infant Nutrition and Health
- Medical Imaging and Pathology Studies
- Acute Lymphoblastic Leukemia research
- Cell Adhesion Molecules Research
- Retinal Development and Disorders
- Ultrasound and Hyperthermia Applications
- Mast cells and histamine
- Retinal Imaging and Analysis
- Neuroscience of respiration and sleep
- RNA modifications and cancer
- Retinal Diseases and Treatments
- Effects and risks of endocrine disrupting chemicals
- Periodontal Regeneration and Treatments
- Chemotherapy-induced organ toxicity mitigation
- Gene Regulatory Network Analysis
University of Rochester
2012-2024
University of Rochester Medical Center
2017-2023
University of Oregon
2022
Litron Laboratories (United States)
2011-2014
The ability to effectively monitor gene mutation and micronucleated reticulocyte (MN-RET) frequency in short-term repeated dosing schedules was investigated using the recently developed flow cytometric Pig-a assay micronucleus analysis. Eight reference genotoxicants three presumed nongenotoxic compounds were studied: chlorambucil, melphalan, thiotepa, cyclophosphamide, azathioprine, 2-acetylaminofluorene, hydroxyurea, methyl methanesulfonate, o-anthranilic acid, sulfisoxazole, sodium...
Abstract While all forms of tobacco exposure have negative health effects, the significance to electronic cigarettes (eCig) is not fully understood. Here, we studied global effects eCig on micro RNA (miRNA) transcriptome in human lung epithelial cells. Primary bronchial (NHBE) cells differentiated at air-liquid interface were exposed liquid. Exposure NHBE any liquid resulted induction oxidative stress-response genes including GCLM, GCLC , GPX2 NQO1 and HO-1 . Vaporization of, and/or presence...
Abstract Radiation therapy for head and neck cancers causes salivary gland dysfunction leading to permanent xerostomia. Limited progress in the discovery of new therapeutic strategies is attributed lack vitro models that mimic function allow high-throughput drug screening. We address this limitation by combining engineered extracellular matrices with microbubble (MB) array technology develop functional tissue mimetics mouse human glands. demonstrate tissues encapsulated within matrix...
Abstract Despite decades of progress, developing minimally invasive bone‐specific drug delivery systems (DDS) to improve fracture healing remains a significant clinical challenge. To address this critical therapeutic need, nanoparticle (NP) DDS comprised poly(styrene‐alt‐maleic anhydride)‐b‐poly(styrene) (PSMA‐b‐PS) functionalized with peptide that targets tartrate‐resistant acid phosphatase (TRAP) and achieves preferential accumulation has been developed. The AR28, glycogen synthase...
The specificity of in vitro mammalian cell genotoxicity assays is low, as they yield a high incidence positive results that are not observed animal and carcinogenicity tests, is, "misleading" or "irrelevant" positives. We set out to develop rapid effective follow-up testing strategy would predict whether apparent micronucleus-inducing effects due clastogenic, aneugenic, secondary irrelevant mode(s) action. Priority was given biomarkers could be multiplexed onto flow cytometric acquisition...
Abstract An international collaborative trial was established to systematically investigate the merits and limitations of a rat in vivo Pig‐a gene mutation assay. The product this is essential for anchoring CD59 plasma membrane, mutations are identified by flow cytometric quantification circulating erythrocytes without cell surface expression. Initial interlaboratory data from rats treated with several potent mutagens have been informative, but time required those analyses (∼20 min per...
Human lung morphogenesis begins by embryonic life and continues after birth into early childhood to form a complex organ with numerous morphologically functionally distinct cell types. Pulmonary organogenesis involves dynamic changes in proliferation, differentiation, migration of specialized cells derived from diverse lineages. Studying the molecular cellular processes underlying formation fully functional requires isolating pulmonary populations during development. We now report novel...
Cisplatin is a cytostatic agent used in the treatment of many types cancer, but its use associated with increased incidences secondary leukemia. We evaluated cisplatin's vivo genotoxic potential by analyzing peripheral blood for Pig-a mutant phenotype erythrocytes and chromosomal damage form micronuclei. Mutant reticuloyte erythrocyte frequencies, based on anti-CD59 antibody labeling flow cytometric analysis, were determined male Sprague Dawley rats treated 28 consecutive days (days 1-28) up...
Previous studies have identified genetic variants associated with bronchopulmonary dysplasia (BPD) in extremely preterm infants. However, findings genome-wide significance been rare, and not replicated. We hypothesized that whole exome sequencing (WES) of premature subjects divergent phenotypic outcomes could facilitate the identification or gene networks contributing disease risk. The Prematurity Respiratory Outcomes Program (PROP) recruited a cohort > 765 infants for markers respiratory...
We recently developed a salivary gland tissue mimetic (SGm), comprised of cells encapsulated in matrix metalloproteinase (MMP)-degradable poly(ethylene glycol) hydrogels within arrays ∼320 µm diameter spherical cavities molded PDMS. The SGm provides functional and physiologically relevant platform well-suited to high-throughput drug screening for radioprotective compounds. However, the utility would benefit from improved retention acinar cell phenotype function. hypothesized that tuning...
Basement membrane (BM) is an essential part of the extracellular matrix (ECM) that plays a crucial role in mechanical support and signaling to epithelial cells during lung development, homeostasis repair. Abnormal composition remodeling ECM have been associated with developmental abnormalities observed multiple pediatric adult respiratory diseases. Collagen VI (COL6) well-studied muscle BM component, but its effect on pulmonary epithelium largely undetermined. We report presence COLVI...
To evaluate whether blood-based genotoxicity endpoints can provide temporal and dose-response data within the low-dose carcinogenic range that could contribute to mode of action (MoA) assessments, we evaluated sensitivity flow cytometry-based micronucleus Pig-a gene mutation assays at below tumorigenic dose rate 50 (TD50) levels. The incidence micronucleated reticulocytes (MN-RET) was used chromosomal damage, frequency CD59-negative (RET(CD59-) ) erythrocytes (RBC(CD59-) served as phenotypic...
Many premature babies who are born with neonatal respiratory distress syndrome (RDS) go on to develop Bronchopulmonary Dysplasia (BPD) and later Post-Prematurity Respiratory Disease (PRD) at one year corrected age, characterized by persistent or recurrent lower tract symptoms frequently related inflammation viral infection. Transcriptomic profiles were generated from sorted peripheral blood CD8+ T cells of preterm full-term infants enrolled consent in the NHLBI Prematurity Outcomes Program...
Progress in the development of salivary gland regenerative strategies is limited by poor maintenance secretory function cells (SGCs) vitro. To reduce precipitous loss function, a modified approach to isolate intact acinar cell clusters and intercalated ducts (AIDUCs), rather than commonly used single suspension, investigated. This isolation yields AIDUCs that maintain many cell-cell cell-matrix interactions glands. Encapsulation matrix metalloproteinase (MMP)-degradable PEG hydrogels...
Abstract Combining multiple genetic toxicology endpoints into a single in vivo study, and/or integrating one or more genotoxicity assays general studies, is attractive because it reduces animal use and enables comprehensive comparative analysis using toxicity, metabolism, pharmacokinetic information from the same animal. This laboratory has developed flow cytometric scoring techniques for monitoring two blood‐based endpoints—micronucleated reticulocyte frequency gene mutation at Pig‐a...
Procarbazine is a genotoxic carcinogen whose DNA ‐damaging activities are not reliably detected in vitro. We evaluated the vivo effects of procarbazine on hematopoietic cells male CD ‐1 mice using multi‐endpoint study design that scored micronucleated reticulocyte ( MN‐RET ) frequency and gene mutation at Pig‐a locus. were treated for 3 days with procarbazine, up to 150 mg/kg/day. Blood samples collected Day exhibited robust induction MN‐RETs , high dose group exhibiting mean 29‐fold...