A5079663292- Neonatal Respiratory Health Research
- Cell Image Analysis Techniques
- Single-cell and spatial transcriptomics
- Congenital heart defects research
- Congenital Diaphragmatic Hernia Studies
- DNA Repair Mechanisms
- Neurobiology and Insect Physiology Research
- Genetics, Aging, and Longevity in Model Organisms
- Epigenetics and DNA Methylation
- Advanced Fluorescence Microscopy Techniques
- Mechanical and Optical Resonators
- Renal and related cancers
- thermodynamics and calorimetric analyses
- Hippo pathway signaling and YAP/TAZ
- Force Microscopy Techniques and Applications
- Genetic and Kidney Cyst Diseases
- Protein Structure and Dynamics
- Immune responses and vaccinations
- Chromatin Remodeling and Cancer
- Photorefractive and Nonlinear Optics
- Optical and Acousto-Optic Technologies
- Plant and Biological Electrophysiology Studies
- Biomedical and Engineering Education
- Neuroscience of respiration and sleep
- Developmental Biology and Gene Regulation
Children's Hospital of Philadelphia
2022-2025
University of Pennsylvania
2022-2025
Philadelphia University
2024
University of Michigan
2019-2022
University at Buffalo, State University of New York
2016-2017
Cilia are specialized structures found on a variety of mammalian cells, with variable roles in the transduction mechanical and biological signals (by primary cilia, PC), as well generation fluid flow motile cilia). Their critical role establishment left-right axis early development is described, defense immune function multiciliated upper airway epithelium. By contrast, detailed analysis ciliary status specific cell types during organogenesis postnatal has received less attention. In this...
The Drosophila type II neuroblast lineages present an attractive model to investigate the neurogenesis and differentiation process as they adapt a similar that in human outer subventricular zone. We perform targeted single-cell mRNA sequencing third instar larval brains study this of NB lineage. Combining prior knowledge, silico analyses, situ validation, our multi-informatic investigation describes molecular landscape from single developmental snapshot. 17 markers are identified...
The longitudinal cellular interactions that drive pulmonary fibrosis are not well understood. To investigate the disease underpinnings associated with onset and progression, we generated a scRNA-seq atlas of lungs from young aged mouse models multiple subtypes Hermansky-Pudlak syndrome (HPS), collection rare autosomal recessive diseases albinism, platelet dysfunction, fibrosis. We have identified an age-dependent increase in SAA3+ inflammatory lung fibroblasts HPS mice, including...
Elucidating cell lineages provides crucial understanding of development. Recently developed sequencing-based techniques enhance the scale lineage tracing but eliminate spatial information offered by conventional approaches. Multi-spectral labeling techniques, such as Brainbow, have potential to identify lineage-related cells in situ. Here, we report nuclear Bitbow (nBitbow), a "digital" version Brainbow that greatly expands color diversity for scoring cells, and suite statistical methods...
ABSTRACT Alveologenesis, the final stage in lung development, substantially remodels distal lung, expanding alveolar surface area for efficient gas exchange. Secondary crest myofibroblasts (SCMF) exist transiently neonatal and are crucial alveologenesis. However, pathways that regulate SCMF function, proliferation temporal identity remain poorly understood. To address this, we purified SCMFs from reporter mice, performed bulk RNA-seq found dynamic changes Hippo-signaling components during We...
Identifying the cellular origins and mapping dendritic axonal arbors of neurons have been century old quests to understand heterogeneity among these brain cells. Current Brainbow based transgenic animals take advantage multispectral labeling differentiate neighboring cells or lineages, however, their applications are limited by color capacity. To improve analysis throughput, we designed Bitbow, a digital format which exponentially expands palette provide tens thousands spectrally resolved...
There is a growing amount of data uncovering the cellular diversity pulmonary circulation and mechanisms governing vascular repair after injury. However, molecular contributing to morphogenesis growth vasculature during embryonic development are less clear. Importantly, deficits in lead significant pediatric lung diseases, indicating need uncover fetal programs promoting growth. To address this, we used transgenic mouse reporter for expression Cxcl12, an arterial endothelial hallmark gene,...
Severe fetal hypoxia poses a significant risk to lung development resulting in severe postnatal complications. Existing chronic animal models lack the ability achieve pathologically reduced oxygen without compromising development, placental blood flow, or maternal health. Using an established model of isolated involving Extrauterine Environment for Neonatal Development (EXTEND), we are able investigate direct impact on development. Oxygen delivery preterm lambs (105-110 days GA) delivered by...
Hermansky-Pudlak syndrome (HPS) is a genetic disorder of endosomal protein trafficking associated with pulmonary fibrosis in specific subtypes, including HPS-1 and HPS-2. Single mutant HPS1 HPS2 mice display increased fibrotic sensitivity while double HPS1/2 exhibit spontaneous aging, which has been attributed to HPS mutations alveolar epithelial type II (AT2) cells. We utilized mouse models human lung tissue investigate mechanisms AT2 cell dysfunction driving remodeling HPS. Starting at 8...
Abstract Identifying the cellular origins and mapping dendritic axonal arbors of neurons have been century old quests to understand heterogeneity among these brain cells. Classical chemical genetic methods take advantage light microscopy sparse labeling unambiguously, albeit inefficiently, trace a few neuronal lineages or reconstruct their morphologies in each sampled brain. To improve analysis throughput, we designed Bitbow, digital format Brainbow which exponentially expands color palette...
Abstract Bacterial pulmonary infections are a major cause of morbidity and mortality in neonates, with less severity older children. Previous studies demonstrated that the DNA CD4 + T cells mouse lung, whose primary responsibility is to coordinate immune response foreign pathogens, differentially methylated neonates compared juveniles. Nevertheless, effect this differential methylation on cell gene expression infection remains unclear. Here we treated E. coli -infected neonatal (4-day-old)...
Bacterial pneumonia in neonates can cause significant morbidity and mortality when compared to other childhood age groups. To understand the immune mechanisms that underlie these age-related differences, we employed a mouse model of Escherichia coli determine dynamic cellular molecular differences responsiveness between (PND 3-5) juveniles 12-18), at 24, 48, 72 hr. Cytokine gene expression from whole lung extracts was also quantified time points, using quantitative RT-PCR. E. challenge...
Abstract Introduction Ataxia telangiectasia (A-T) is an autosomal recessive neurodegenerative disease with widespread systemic manifestations and marked variability in clinical phenotypes. In this study, we sought to determine whether transcriptomic profiling of peripheral blood mononuclear cells (PBMCs) defines subsets individuals A-T beyond mild classic phenotypes, enabling identification novel features for classification treatment response therapy. Methods Participants ( n = 77), 13),...
Cilia are specialized structures found on a variety of mammalian cells, with variable roles in the transduction mechanical and biological signals (by primary cilia, PC), as well generation fluid flow motile cilia). Their critical role establishment left-right axis early development is described, innate immune function multiciliated upper airway epithelium. By contrast, dynamics ciliary status during organogenesis postnatal largely unknown. In this study, we define progression within...
In recent years, advancements in microscope design have allowed faster, higher resolution imaging of all types biological samples. Custom designs rapidly seen adoption, enabled by a rapid growth open source software. this report, we present custom, source, hardware which provides 2 16-bit high-speed analog outputs as well breakouts for GPIO connections to the inexpensive and well-supported microcontroller (the $4 Raspberry Pi Pico). We provide firmware interfacing device with software...
Hermansky-Pudlak syndrome (HPS) is a genetic disorder of endosomal protein trafficking associated with pulmonary fibrosis in specific subtypes, including HPS-1 and HPS-2. Single mutant HPS1 HPS2 mice display increased fibrotic sensitivity while double HPS1/2 exhibit spontaneous aging, which has been attributed to HPS mutations alveolar epithelial type II (AT2) cells. We utilized mouse models human lung tissue investigate mechanisms AT2 cell dysfunction driving remodeling HPS. Starting at 8...
Abstract The study of neuron morphology requires robust and comprehensive methods to quantify the differences between neurons different subtypes animal species. Several software packages have been developed for analysis tracing results stored in standard SWC format. However, providing relatively simple quantifications their non-extendable architecture prohibit use advanced data visualization. We nGauge , a Python toolkit support parsing data. As an application programming interface (API),...
Abstract In adults, there is a growing amount of data uncovering the cellular diversity pulmonary circulation and mechanisms governing vascular repair after injury, however, molecular contributing to morphogenesis growth vasculature during embryonic development are less clear. Importantly, deficits in lead large number lung diseases children, indicating need uncover fetal programs that promote growth. To address this, we used transgenic mouse reporter for expression Cxcl12 , an arterial...