A5081800135- Cystic Fibrosis Research Advances
- Epigenetics and DNA Methylation
- Neonatal Respiratory Health Research
- Genomics and Chromatin Dynamics
- Cancer-related molecular mechanisms research
- Advanced biosensing and bioanalysis techniques
- CRISPR and Genetic Engineering
- Kruppel-like factors research
- Animal Genetics and Reproduction
- RNA Research and Splicing
- Single-cell and spatial transcriptomics
- Genetic Syndromes and Imprinting
- Cancer-related gene regulation
- RNA modifications and cancer
- Energy Harvesting in Wireless Networks
- Congenital Ear and Nasal Anomalies
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Neuropeptides and Animal Physiology
- Congenital Diaphragmatic Hernia Studies
- Genetics and Neurodevelopmental Disorders
- Heart Failure Treatment and Management
- Sperm and Testicular Function
- MicroRNA in disease regulation
- Pluripotent Stem Cells Research
- RNA Interference and Gene Delivery
University of Pennsylvania
2024-2025
Case Western Reserve University
2018-2024
University School
2022-2024
California University of Pennsylvania
2024
Human Genome Sciences (United States)
2021
A "universal strategy" replacing the full-length
The basolateral amygdala (BLA) is essential for assigning positive or negative valence to sensory stimuli. Noxious stimuli that cause pain are encoded by an ensemble of
The differentiated functions of the human airway epithelium are coordinated by a complex network transcription factors. These include pioneer factors Forkhead box A1 and A2 (FOXA1 FOXA2), which well studied in several tissues, but their role epithelial cells is poorly characterized. Here, we define cistrome FOXA1 FOXA2 primary bronchial (HBE) chromatin immunoprecipitation with deep-sequencing (ChIP-seq). Next, siRNA-mediated depletion each factor used to investigate transcriptome RNA-seq. We...
The CFTR gene lies within an invariant topologically associated domain (TAD) demarcated by CTCF and cohesin, but shows cell-type specific control mechanisms utilizing different cis-regulatory elements (CRE) the TAD. Within respiratory epithelium, more than one cell type expresses molecular controlling its transcription are likely divergent between them. Here, we determine how two extragenic CREs that prominent in epithelial cells lung, regulate expression of gene. We showed earlier these...
The human epididymis is poorly studied due to the lack of availability tissue samples. Our understanding its structure and function depends upon anatomical histological observations archived material.
We identified and characterized multiple cell-type selective enhancers of the CFTR gene promoter in previous work demonstrated active looping these elements to promoter. Here we address impact genomic spacing on enhancer:promoter interactions expression. Using CRISPR/Cas9, generated clonal cell lines with deletions between -35 kb airway enhancer 16HBE14o
Autism spectrum disorder (ASD) is a highly heterogenous neurodevelopmental with numerous genetic risk factors. Notably, disproportionate number of genes encode transcription regulators including factors and proteins that regulate chromatin. Here, we tested the function nine such ASD-linked by depleting them in primary cultured neurons. We then defined resulting gene expression disruptions using RNA-sequencing effects on neuronal firing multielectrode array recordings. identified shared...
The cystic fibrosis transmembrane conductance regulator (CFTR) gene lies within a topologically associated domain (TAD) in which multiple cis-regulatory elements (CREs) and transcription factors (TFs) regulate its cell-specific expression. CREs are recruited to the promoter by looping mechanism that depends upon both architectural proteins specific TFs. An siRNA screen identify TFs coordinating CFTR expression airway epithelial cells suggested an activating role for BTB CNC homolog 1...
Abstract The airway epithelial cell line, 16HBE14o − , is an important model for studying disease. cells were originally generated from primary human bronchial by SV40‐mediated immortalization, a process that associated with genomic instability through long‐term culture. Here, we explore the heterogeneity of these cells, respect to expression cystic fibrosis transmembrane conductance regulator (CFTR) transcript and protein. We isolate clones stably higher lower levels CFTR in comparison bulk...
Robust protocols to examine 3D chromatin structure have greatly advanced knowledge of gene regulatory mechanisms. Here we focus on the cystic fibrosis transmembrane conductance regulator (CFTR) gene, which provides a paradigm for validating models regulation built upon genome-wide analysis. We mechanisms by multiple cis-regulatory elements (CREs) at CFTR coordinate its expression in intestinal epithelial cells. Using CRISPR/Cas9 remove CREs, individually and tandem, followed assays...
Abstract The availability of robust protocols to differentiate induced pluripotent stem cells (iPSCs) into many human cell lineages has transformed research the origins disease. efficacy differentiating iPSCs specific cellular models is influenced by factors including both intrinsic and extrinsic features. Among most challenging generation bronchial epithelium at air‐liquid interface (HBE‐ALI), which gold standard for studies respiratory diseases cystic fibrosis. Here, we perform open...
A complex network of transcription factors regulates genes involved in establishing and maintaining key biological properties the human airway epithelium. However, detailed knowledge contributing is incomplete. Here we characterize role Krüppel-like factor 5 (KLF5), controlling essential pathways epithelial cell identity function lung. RNA-seq following siRNA-mediated depletion KLF5 Calu-3 lung line identified significant enrichment encoding chemokines cytokines proinflammatory response also...
Abstract Background Pancreatic fibrosis is an early diagnostic feature of the common inherited disorder cystic (CF). Many people with CF (pwCF) are pancreatic insufficient from birth and replacement acinar tissue lesions a progressive phenotype that may later lead to diabetes. Little known about initiating events in fibrotic process though it be sequela inflammation ducts resulting loss CFTR impairing normal fluid secretion. Here we use sheep model ( −/− ) examine evolution disease through...
SUMMARY A cell’s ability to respond and adapt environmental stimuli relies in part on transcriptional programs controlled by histone proteins. Histones affect transcription through numerous mechanisms including replacement with variant forms that carry out specific functions. We recently identified the first widely expressed H2B variant, H2BE found it promotes is critical for neuronal function long-term memory. However, how regulated extracellular whether controls activity-dependent cellular...
ABSTRACT Individuals with monoallelic pathogenic variants in the histone lysine methyltransferase DOT1L display global developmental delay and varying congenital anomalies. However, impact of loss remains unclear. Here, we present a largely female cohort 11 individuals delays dysmorphic facial features. We found that include missense clustered catalytic domain, frameshift, stop-gain variants. demonstrate specific cause activity therefore sought to define effects decreased function. Using...
Single cell RNA-sequencing has accurately identified types within the human airway that express Cystic Fibrosis Transmembrane Conductance regulator (CFTR) gene. Low abundance CFTR transcripts are seen in many secretory cells, while high levels restricted to rare pulmonary ionocytes. Here we focus on mechanisms coordinating basal expression compartment. Cell-selective regulation of is achieved its invariant topologically associating domain by recruitment cis-regulatory elements (CREs). CRE...
Highly effective modulator therapies for cystic fibrosis (CF) make it a treatable condition many people. However, although CF respiratory illness occurs after birth, other organ systems particularly in the digestive tract are damaged before birth. We use an ovine model of to investigate utero origins disease since sheep closely mirrors critical aspects human development. Wildtype (WT) and
The precise molecular events initiating human lung disease are often poorly characterized. Investigating prenatal that may underlie in later life is challenging man, but insights from the well-characterized sheep model of development valuable. Here, we determine transcriptomic signature wild-type (WT) and use a cystic fibrosis (CF) to characterize associated changes gene expression through pseudoglandular, canalicular, saccular, alveolar stages growth differentiation. Using ontology process...
Cell-specific and developmental mechanisms contribute to expression of the cystic fibrosis transmembrane conductance regulator (CFTR) gene; however, its regulation is poorly understood. Here we use human induced pluripotent stem cells differentiated into pseudostratified airway epithelial study these mechanisms.