A5085358112- Medical Imaging and Pathology Studies
- Glioma Diagnosis and Treatment
- Meningioma and schwannoma management
- Brain Metastases and Treatment
- Digestive system and related health
- Cancer Cells and Metastasis
- Single-cell and spatial transcriptomics
- Angiogenesis and VEGF in Cancer
- Neonatal Respiratory Health Research
- Cell Adhesion Molecules Research
- Tracheal and airway disorders
- Cellular Mechanics and Interactions
- Congenital heart defects research
- Lymphatic System and Diseases
- Cancer Genomics and Diagnostics
- Zebrafish Biomedical Research Applications
- Cancer, Hypoxia, and Metabolism
- Chronic Obstructive Pulmonary Disease (COPD) Research
- Parasitic infections in humans and animals
- RNA modifications and cancer
- Pulmonary Hypertension Research and Treatments
- 3D Printing in Biomedical Research
- Hematopoietic Stem Cell Transplantation
- Congenital Anomalies and Fetal Surgery
- Pleural and Pulmonary Diseases
University of California, San Francisco
2021-2024
City College of San Francisco
2022
Cornell University
2013-2021
Weill Cornell Medicine
2017-2021
Howard Hughes Medical Institute
2013
Dana-Farber Cancer Institute
2013
BMP4 produced by endothelial cells promotes thymic regeneration after acute damage activating FOXN1 and its downstream targets.
Chronic obstructive pulmonary disease (COPD) is marked by airway inflammation and airspace enlargement (emphysema) leading to airflow obstruction eventual respiratory failure. Microvasculature dysfunction associated with COPD/emphysema. However, it not known if abnormal endothelium drives COPD/emphysema pathology and/or correcting endothelial has therapeutic potential. Here, we show the centrality of cells pathogenesis in human tissue using an elastase-induced murine model emphysema....
Angiocrine factors, such as Notch ligands, supplied by the specialized endothelial cells (ECs) within bone marrow and splenic vascular niche play an essential role in modulating physiology of adult hematopoietic stem progenitor (HSPCs). However, relative contribution various specifically jagged-2, to homeostasis HSPCs is unknown. Here, we show that under steady state, jagged-2 differentially expressed tissue-specific beds, but its expression induced niches after myelosuppressive injury. We...
The gastrointestinal tract relies on the production, maturation, and transit of mucin to protect against pathogens lubricate epithelial lining. Although molecular cellular mechanisms that regulate production movement are beginning be understood, upstream signals contribute regulation remain unclear. Here, we report inflammatory cytokine tumor necrosis factor (TNF), generated by epithelium, contributes homeostasis regulating both cell differentiation cystic fibrosis transmembrane conductance...
Abstract Meningiomas are the most common primary intracranial tumors. Treatments for patients with meningiomas limited to surgery and radiotherapy, systemic therapies remain ineffective or experimental. Resistance radiotherapy is in high-grade cell types signaling mechanisms that drive meningioma tumorigenesis resistance incompletely understood. Here, we report NOTCH3 drives find perivascular NOTCH3+ stem cells conserved across from humans, dogs, mice. Integrating single-cell transcriptomics...
Epithelial organoids derived from intestinal tissue, called enteroids, recapitulate many aspects of the organ in vitro and can be used for biological discovery, personalized medicine, drug development. Here, we interrogated cell signaling environment within developing human intestine to identify niche cues that may important epithelial development homeostasis. We identified an EGF family member, EPIREGULIN (EREG), which is robustly expressed crypt. Enteroids generated grown standard culture...
ABSTRACT Identifying immune correlates of protection is important to develop vaccines against infectious diseases. We designed a novel, universally applicable strategy profile the antibody (Ab) repertoire protected vaccine recipients, using recombinant phages encoding random peptide libraries. The new approach, termed “protection-linked (PL) biopanning,” probes Ab paratopes vaccinees versus those with failure. As proof concept, we screened plasma samples from vaccinated rhesus macaques (RMs)...
Meningiomas are the most common primary intracranial tumors
Transplanting vascular endothelial cells (ECs) to support metabolism and express regenerative paracrine factors is a strategy treat vasculopathies promote tissue regeneration. However, transplantation strategies have been challenging develop, because ECs are difficult culture little known about how direct them stably integrate into vasculature. Here we show that only amniotic could convert maintain EC gene expression. Even so, these converted perform sub-optimally in studies. Constitutive...
Abstract A key aspect of nutrient absorption is the exquisite division labor across length small intestine, with individual classes micronutrients taken up at different positions. For millennia, intestine was thought to comprise three segments indefinite borders: duodenum, jejunum, and ileum. By examining fine-scale longitudinal segmentation mouse human intestines, we identified transcriptional signatures upstream regulatory factors that define five domains absorption, distinct from...
Abstract Objective Endothelial cells form vascular beds in all organs and are exposed to a range of mechanical forces that regulate cellular phenotype. We sought determine the role endothelial luminal surface stiffness tissue‐specific mechanotransduction laminar shear stress microvascular mouse arachidonic acid mediating this response. Methods Microvascular were subjected at 4 dynes/cm 2 for 12 hours parallel plate flow chambers enabled real‐time optical microscopy atomic force measurements...
<p>Supplementary Fig. 2. Single-cell RNA sequencing of dog meningiomas. A, counts across UMAP clusters from meningioma samples analyzed using single-cell sequencing. B, showing shaded by sample origin. C, cell cycle analysis samples. D-E, Heatmapt and feature plots differentially expressed genes Colors as in A. F, Magnetic resonance imaging (MRI, left) or H&E images (right) spontaneous Scale bars, 100µm. See also Supplementary Table 2.</p>
<p>Supplementary Fig. 3. NOTCH3 immunohistochemistry across meningioma WHO grades. expression is predominantly restricted to the perivascular niche in grade 1 meningiomas A, but extends beyond 2 B and 3 C. SF numbers indicate individual meningiomas. defined using histological criteria. Representative of n=10 per grade. Scale bar, 100µm.</p>
<p>Supplementary Fig. 16. NOTCH3 inhibition blocks meningioma xenograft growth without causing toxicity. A, A NOTCH1 negative regulatory region neutralizing antibody (αNRR1), but not αNRR3, causes diarrhea and rash resulting in weight loss mice harboring xenografts. Antibodies were delivered using biweekly IP injection. Student’s <i>t</i> tests. B, The -secretase inhibitor LY-411575 (GSI) daily injection C, attenuates the of CH-175MN (left) or IOMM-Lee (right) xenografts...
<p>Supplementary Fig. 4. WHO grade 1 meningioma immunofluorescence microscopy for NOTCH3 and the mural cell marker SMA. expression is restricted to perivascular niche colocalizes with cells in meningiomas histology. SF numbers indicate individual meningiomas. defined using histological criteria. Representative of n=10 Scale bars, 10µm.</p>
<p>Supplementary Fig. 1. Single-cell RNA sequencing of human meningiomas with loss chromosome 22q. A, counts across UMAP clusters from meningioma samples 22q analyzed using single-cell sequencing. B, showing shaded by sample origin. C, Stacked bar plots the distribution (red) samples. D, and stacked plot cell cycle analysis E-G, Heatmap feature differentially expressed genes Colors as in A. See also Supplementary Table G, Feature expression (SSTR2, PTGDS) or cancer stem-cell markers...
<div>Abstract<p>Meningiomas are the most common primary intracranial tumors. Treatments for patients with meningiomas limited to surgery and radiotherapy, systemic therapies remain ineffective or experimental. Resistance radiotherapy is in high-grade cell types signaling mechanisms that drive meningioma tumorigenesis resistance incompletely understood. Here, we report NOTCH3 drives find perivascular NOTCH3<sup>+</sup> stem cells conserved across from humans, dogs,...
<p>Supplementary Fig. 14. Meningioma invasion of Virchow-Robin spaces. A, H&E low magnification (top) and high (box, bottom) images human meningioma into perivascular fluid-filled cavities surrounding perforating vasculature the brain. Densely cellular is shown at top each image, islands tumor within brain parenchyma (dashed lines, are bottom image. Scale bars, 100µm. B, Low IHC for marker GFAP validates unlabeled cells spaces without direct itself. C, mural cell SMA or SSTR2A...
<p>Supplementary Fig. 12. Single-cell RNA sequencing of human and mouse cells from meningioma xenografts. A, counts across experimental conditions, biological replicates (samples), UMAP clusters CH-157MN xenograft analyzed using single-cell sequencing. B, replicates, phases the cell cycle Colors rows (samples) as in A. C, D, Stacked bar plots showing distribution replicates. E, C.</p>
<p>Supplementary Fig. 6. WHO grade 3 meningioma immunofluorescence microscopy for NOTCH3 and the mural cell marker SMA. is expressed in out of perivascular niche, colocalizes with cells meningiomas histology. SF numbers indicate individual meningiomas. Representative n=10 defined using histological criteria. Scale bars, 10µm.</p>