A5089654223- Developmental Biology and Gene Regulation
- Wnt/β-catenin signaling in development and cancer
- Renal and related cancers
- Microtubule and mitosis dynamics
- Congenital heart defects research
- Cancer-related gene regulation
- Hedgehog Signaling Pathway Studies
- Neonatal Respiratory Health Research
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Congenital Diaphragmatic Hernia Studies
- Immune Response and Inflammation
- Cervical Cancer and HPV Research
- Chromosomal and Genetic Variations
- CRISPR and Genetic Engineering
- Chronic Kidney Disease and Diabetes
- 3D Printing in Biomedical Research
- Hippo pathway signaling and YAP/TAZ
- Transgenic Plants and Applications
- Tracheal and airway disorders
- Renal cell carcinoma treatment
- Genetics and Neurodevelopmental Disorders
- Cancer-related molecular mechanisms research
- Advanced Fluorescence Microscopy Techniques
- Acute Kidney Injury Research
- Plant tissue culture and regeneration
Cincinnati Children's Hospital Medical Center
2015-2025
University of Cincinnati Medical Center
2006-2025
University of Cincinnati
2011-2024
Children's Medical Center
2019-2020
Children's Hospital & Medical Center
2014
University of Virginia
2005
University of Minnesota
1995-2000
Fox Valley Surgical Associates
1991
Significance Statement Because current management of the rapid renal-function decline in AKI is merely supportive, deeper understanding AKI-perturbed molecular pathways needed to identify targets with potential lead improved treatment. In a murine model, authors used single-cell RNA sequencing, single-molecule situ hybridization, and protein expression analyses create first comprehensive renal cell type–specific transcriptional profiles for multiple stages. Their findings revealed marked...
Abstract The maternal transcription factor VegT is important for establishing the primary germ layers in Xenopus. In previous work, we showed that vegetal masses of embryos lacking do not produce mesoderm-inducing signals and mesoderm formation these occurred ectopically, from area rather than equatorial zone blastula. Here have increased efficiency depletion mRNA studied effects on formation. We find required 90% mesodermal tissue, as measured by expression markers MyoD, cardiac actin,...
ABSTRACT During cleavage stages, maternal VegT mRNA and protein are localized to the Xenopus embryo’s vegetal region from which endoderm will arise where several zygotic gene transcripts be localized. Previous loss-of-function experiments on this T-box transcription factor suggested a role for in formation. Here, we test whether is required initiate formation using loss of function approach. We find that endodermal genes, Bix1, Bix3, Bix4, Milk (Bix2), Mix.1, Mix.2, Mixer, Xsox17α, Gata4,...
In previous work, we demonstrated that maternally encoded beta-catenin, the vertebrate homolog of armadillo, is required for formation dorsal axial structures in early Xenopus embryos (Heasman, J., Crawford, A., Goldstone, K., Garner-Hamrick, P., Gumbiner, B., Kintner, C., Yoshida-Noro, C. and Wylie, (1994). Cell 79, 791-803). Here investigated, firstly, role(s) beta-catenin spatial terms, different regions embryo, by injecting mRNA into individual blastomeres beta-catenin-depleted at 32...
We created a human stomach-on-a-chip by using an innovative microfluidic imaging platform housing gastric organoids (hGOs) with peristaltic luminal flow.
Abstract Examining kidney fibrosis is crucial for mechanistic understanding and developing targeted strategies against chronic disease (CKD). Persistent fibroblast activation tubular epithelial cell (TEC) injury are key CKD contributors. However, cellular transcriptional landscapes of specific activated clusters remain elusive. Here, we analyzed single transcriptomic profiles two clinically relevant models which induced robust parenchymal remodeling. We dissected the molecular stroma newly...
Since the three main pathways (the Wnt, VegT and BMP pathways) involved in organizer axis formation Xenopus embryo are now characterized, challenge is to understand their interactions. Here comparisons were made. Firstly, we made a systematic comparison of expression zygotic genes sibling wild-type, VegT-depleted (VegT–), β-catenin-depleted (β-catenin–) double depleted (VegT–/β-catenin–) embryos placed early into specific groups. In first group some genes, including chordin, noggin cerberus,...
Xenopus Vg1, a transforming growth factor β (Tgfβ)family member, was one of the first maternally localized mRNAs identified in vertebrates. Its restriction to vegetal pole egg made it ideal candidate be mesoderm-inducing signal released by cells, but its function vivo has never been resolved. We show that Vg1 is essential for embryonic development, and required mesoderm induction expression several key Bmp antagonists. Although original transcript does not rescue Vg1-depleted embryos, we...
In the early Xenopus embryo, dorsal axis is specified by a Wnt signal transduction pathway, involving movement of β-catenin into cell nuclei and its functional association with LEF-type transcription factor XTcf3. The subsequent function XTcf3 uncertain. Overexpression data has suggested that it can be both an activator repressor downstream genes. mRNA synthesized during oogenesis in stored egg. To identify role specification, we depleted this maternal store full-grown oocytes using...
Current models of canonical Wnt signaling assume that a pathway is active if beta-catenin becomes nuclearly localized and target genes are transcribed. We show that, in Xenopus, maternal LRP6 essential such pathway, playing pivotal role causing expression the organizer siamois Xnr3, establishing dorsal axis. provide evidence acts by degrading axin protein during early cleavage stage development. In full-grown oocyte, before maturation, we find levels also regulated Wnt11 LRP6. and/or...
Multiphoton fabrication is a powerful technique for three-dimensional (3D) printing of structures at the microscale. Many polymers and proteins have been successfully structured patterned using this method. Type I collagen comprises large part extracellular matrix most tissue types widely used cellular scaffold material engineering. Current methods creating scaffolds do not allow control local geometry on scale. This means environment experienced by cells may be made up native but unrelated...
Neutrophils are the first line of cellular defense in response to infections and inflammatory injuries. However, neutrophil activation accumulation into tissues trigger tissue damage due release a plethora toxic oxidants proteases, cause acute lung injury (ALI). Despite its clinical importance, molecular regulation migration is poorly understood. The small GTPase Rap1b generally viewed as positive regulator immune cell functions by controlling bidirectional integrin signaling. we found that...
Abstract Biologic tissues are generally opaque due to optical properties that result in scattering and absorption of light. Preparation for microscopy often involves sectioning a thickness 50‐100 µm, the practical limits light penetration recovery. A researcher who wishes image whole tissue must acquire potentially hundreds individual sections before rendering them into three‐dimensional volume. Clearing removes strongly light‐scattering light‐absorbing components equalizes refractive index...
Biliary atresia (BA) is a fibroinflammatory obstruction of the extrahepatic biliary tree in neonates. While intrahepatic bile duct proliferation universal at diagnosis, paucity develops later. We hypothesized that polarized T helper lymphocyte responses orchestrate progression injury this disease. Interleukin 17A (IL-17A)-green fluorescent protein, cluster differentiation 11c (CD11c)/diphtheria toxin receptor, and IL-17 receptor A−/− mice were used to examine T-lymphocyte polarization,...
Abstract Persistent HPV16 infection is a major cause of the global cancer burden. The viral life cycle dependent on differentiation program stratified squamous epithelium, but landscape keratinocyte subpopulations which support distinct phases has yet to be elucidated. Here, single cell RNA sequencing infected compared uninfected organoids identifies twelve populations, with subset mapped reconstruct their respective 3D geography in epithelium. Instead conventional terminally differentiated...
In vertebrates, germ layer specification represents a critical transition where pluripotent cells acquire lineage-specific identities. We identify the maternal transcription factors Foxi2 and Sox3 to be pivotal master regulators of ectodermal in Xenopus . Ectopic co-expression prospective endodermal tissue induces expression markers while suppressing mesendodermal markers. Transcriptomics analyses reveal that jointly independently regulate hundreds target genes. During early cleavage stages,...