A5005065116- Axon Guidance and Neuronal Signaling
- Neonatal Respiratory Health Research
- Hedgehog Signaling Pathway Studies
- Pulmonary Hypertension Research and Treatments
- Congenital Diaphragmatic Hernia Studies
- Glycogen Storage Diseases and Myoclonus
- Inflammatory Myopathies and Dermatomyositis
- Respiratory Support and Mechanisms
- Catalytic Cross-Coupling Reactions
- Developmental Biology and Gene Regulation
- Neurogenesis and neuroplasticity mechanisms
- Bone Metabolism and Diseases
- Immune cells in cancer
- Renal Diseases and Glomerulopathies
- Glycosylation and Glycoproteins Research
- Angiogenesis and VEGF in Cancer
- Hippo pathway signaling and YAP/TAZ
- Antibiotics Pharmacokinetics and Efficacy
- Chemical synthesis and alkaloids
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Congenital heart defects research
- Congenital Heart Disease Studies
- Chronic Lymphocytic Leukemia Research
- Cyclopropane Reaction Mechanisms
- Zebrafish Biomedical Research Applications
Children's Hospital of Philadelphia
2020-2025
University of Pennsylvania
2011-2025
National Institutes of Health
2012-2025
National Cancer Institute
2024-2025
Center for Cancer Research
2024
University of California, San Francisco
2016-2022
Penn Center for AIDS Research
2020-2022
National Human Genome Research Institute
2012
Philadelphia University
2011
Pulmonary endothelial cells (ECs) are an essential component of the gas exchange machinery lung alveolus. Despite this, extent and function EC heterogeneity remains incompletely understood. Using single-cell analytics, we identify multiple populations in mouse lung, including macrovascular endothelium (maEC), microvascular (miECs), a new population have termed Car4-high ECs. ECs express unique gene signature, ligand-receptor analysis indicates they primed to receive reparative signals from...
Transitioning lung for postnatal life The is a complex organ composed of multiple cell types, and its alveolus serves as the functional unit gas exchange. alveolar type 1 (AT1) an active signaling hub in developing mouse human lung. Zepp et al. generated comprehensive single-cell atlas murine identified differentiation cell-to-cell communication transitions to air breathing. AT1 cells spatially aligned with stromal progenitors formed that preferentially communicated transient,...
Disruption of pulmonary vascular homeostasis is a central feature viral pneumonia, wherein endothelial cell (EC) death and subsequent angiogenic responses are critical determinants the outcome severe lung injury. A more granular understanding fundamental mechanisms driving reconstitution endothelium necessary to facilitate therapeutic repair. Here, we demonstrated that TGF-β signaling through TGF-βR2 (transforming growth factor–β receptor 2) activated in ECs upon influenza infection, mice...
Following acute injury, the capillary vascular bed in lung must be repaired to reestablish gas exchange with external environment. Little is known about transcriptional and signaling factors that drive pulmonary endothelial cell (EC) proliferation subsequent regeneration of capillaries, as well their response stress. Here, we show transcription factor Atf3 essential for regenerative mouse endothelium after influenza infection. expression defines a subpopulation ECs enriched genes involved...
Cell segregation is the process by which cells self-organize to establish developmental boundaries, an essential step in tissue formation. a common outcome of Eph/ephrin signaling, but mechanisms remain unclear. In craniofrontonasal syndrome, X-linked mosaicism for ephrin-B1 expression has been hypothesized lead aberrant Eph/ephrin-mediated cell segregation. Here, we use mouse genetics exploit study mammalian embryo and integrate live-cell imaging examine underlying cellular molecular...
Pathological glomerular hyposialylation has been implicated in certain unexplained glomerulopathies, including minimal change nephrosis, membranous glomerulonephritis, and IgA nephropathy. We studied our previously established mouse model carrying a homozygous mutation the key enzyme of sialic acid biosynthesis, N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase. Mutant mice died before postnatal day 3 (P3) from severe glomerulopathy with podocyte effacement segmental basement...
C-O activation of mesylates by a palladium catalyst and subsequent cross-coupling with potassium cyclopropyltrifluoroborate have been achieved high yield. Both electron-enriched electron-deficient aryl are suitable electrophilic partners for the Suzuki-Miyaura reaction. The scope was successfully extended to heteroaryl yields up 94%.
Craniofrontonasal syndrome (CFNS) is a rare X-linked disorder characterized by craniofacial, skeletal, and neurological anomalies caused mutations in EFNB1. Heterozygous females are more severely affected CFNS than hemizygous males, phenomenon called cellular interference that results from EPHRIN-B1 mosaicism. In Efnb1 heterozygous mice, mosaicism for cell sorting severe phenotypes but how craniofacial dysmorphology arises segregation unknown etiology therefore remains poorly understood....
Although human induced pluripotent stem cells (hiPSCs) hold great potential for the study of diseases affecting disparate cell types, they have been underutilized in seeking mechanistic insights into pathogenesis congenital craniofacial disorders. Craniofrontonasal syndrome (CFNS) is a rare X-linked disorder caused by mutations EFNB1 and characterized craniofacial, skeletal, neurological anomalies. Heterozygous females are more severely affected than hemizygous males, phenomenon termed...
Abstract Following acute injury, the capillary vascular bed in lung must be repaired to reestablish gas exchange with external environment. Little is known about transcriptional and signaling factors that drive pulmonary endothelial cell (EC) proliferation subsequent regeneration of capillaries, as well their response stress. Here, we show transcription factor Atf3 essential for regenerative mouse endothelium after influenza infection. expression defines a subpopulation ECs enriched genes...
Summary Functional regeneration of the lung’s gas exchange surface following injury requires coordination a complex series cell behaviors within alveolar niche. Using multi-modal approach, we have mapped temporal sequencing mouse lung after acute viral injury, demonstrating that this response is asynchronously phased across different cellular compartments. This longitudinal atlas has produced catalogue new states reflect transient and persistent transcriptional alterations in daughter cells...
Abstract Background: Variation in facial shape may arise from the combinatorial or overlapping actions of paralogous genes. Given its many members, and expression functions, EPH receptor family is a compelling candidate source craniofacial morphological variation. We performed detailed morphometric analysis an allelic series E14.5 Ephb1‐3 mutants to determine effect each gene on morphology. Results: found that Ephb1 , Ephb2 Ephb3 genotypes significantly influenced shape, but effects were...
Abstract The arylated cyclopropanes are of biological interest.
Abstract Craniofrontonasal syndrome (CFNS) is a rare X-linked disorder characterized by craniofacial, skeletal, and neurological anomalies caused mutations in EFNB1 . Heterozygous females are more severely affected CFNS than hemizygous male patients, phenomenon called cellular interference that correlated with cell segregation resulting from EPHRIN-B1 mosaicism. Efnb1 heterozygous mutant mice also exhibit severe phenotypes males as well segregation, but how craniofacial dysmorphology arises...
Efnb1 +/− heterozygous mice phenocopy many craniofacial characteristics of craniofrontonasal syndrome (CFNS), a disorder caused by EFNB1 loss function mutations. Because ephrin‐B1 is expressed strongly throughout the developing telencephalon in mice, we hypothesized that hypertelorism (increased distance between eyes) could be secondary to early changes form underlying cerebral cortex. This stems from common expectation intramembranously ossified bones surrounding brain can accommodate...
EPHRIN-B1 mutations underlie craniofrontonasal syndrome (CFNS), and signaling interactions between ligand the EPHB1, EPHB2, EPHB3 receptors are presumed to be critical for normal craniofacial development. However, our understanding of relative spatial contribution each receptor facial morphogenesis remains incomplete. Here, we expand upon previous work by providing a detailed morphometric analysis an E14.5 allelic seriesof Ephb1, Ephb2, Ephb3 null mouse mutants. We assess impact individual...