A5056189721- Cancer Cells and Metastasis
- Neonatal Respiratory Health Research
- Immune cells in cancer
- Epigenetics and DNA Methylation
- Congenital Diaphragmatic Hernia Studies
- Phagocytosis and Immune Regulation
- Renal and related cancers
- Telomeres, Telomerase, and Senescence
- Diabetes and associated disorders
- Wnt/β-catenin signaling in development and cancer
- Pluripotent Stem Cells Research
- Cancer, Hypoxia, and Metabolism
- Autophagy in Disease and Therapy
- Single-cell and spatial transcriptomics
- FOXO transcription factor regulation
- ATP Synthase and ATPases Research
- Extracellular vesicles in disease
- Neuroblastoma Research and Treatments
- Cancer-related gene regulation
- Congenital heart defects research
- Digestive system and related health
- Mitochondrial Function and Pathology
- Ubiquitin and proteasome pathways
University of Pennsylvania
2020-2025
California Institute for Regenerative Medicine
2022-2024
Lung Institute
2020
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...
Abstract The initiation and progression of cancer are intricately linked to the tumor microenvironment (TME). Understanding function specific cancer-TME interactions poses a major challenge due in part complexity vivo microenvironment. Here we predict from single cell transcriptomic maps both human colorectal cancers (CRCs) mouse CRC models, ask how these altered organoid (tumoroid) cultures, functionally recapitulate myeloid-carcinoma vitro. Tumoroid cultures suppress gene expression...
Abstract Inflammation induced by lung infection is a double-edged sword, moderating both anti-viral and immune pathogenesis effects; the mechanism of latter not fully understood. Previous studies suggest vasculature involved in tissue injury. Here, we report that expression Sparcl1, secreted matricellular protein, upregulated pulmonary capillary endothelial cells (EC) during influenza-induced Endothelial overexpression SPARCL1 promotes detrimental inflammation, with inducing ‘M1-like’...
Acute respiratory distress syndrome is associated with a robust inflammatory response that damages the vascular endothelium, impairing gas exchange. While restoration of microcapillaries critical to avoid mortality, therapeutic targeting this process requires greater understanding endothelial repair mechanisms. Here, we demonstrate lung endothelium possesses substantial regenerative capacity and lineage tracing reveals native source after influenza injury. Ablation chicken ovalbumin upstream...
Colorectal cancer (CRC) is a leading cause of cancer-related deaths, with the majority cases initiated by inactivation APC tumour suppressor. This results in constitutive activation canonical WNT pathway transcriptional effector ß-catenin, along induction feedback inhibitors, including extracellular palmitoleoyl-protein carboxylesterase NOTUM which antagonises WNT-FZD receptor-ligand interactions. Here, we sought to evaluate effects activity on CRC as function driver mutation landscape.
SUMMARY Colorectal cancer (CRC) is a leading cause of deaths, predominantly initiated by genetic inactivation the APC tumor suppressor. Current dogma holds that promotes tumorigenesis via hyperactivation WNT pathway transcriptional effector, β-CATENIN. Although β-CATENIN activation required for initiation, activating mutations in are infrequent. Here, we ask what underlies selective pressure comparing oncogenic effects loss to hyperactivation. We find activates β-CATENIN-independent fetal...
Abstract Inflammation upon infectious lung injury is a double-edged sword: while tissue-infiltrating immune cells and cytokines are necessary to control infection, these same factors often aggravate injury. Full appreciation of both the sources targets inflammatory mediators required facilitate strategies maintain antimicrobial effects minimizing off-target epithelial endothelial damage. Recognizing that vasculature centrally involved in tissue responses we observed pulmonary capillary (ECs)...
The identity of the intestinal stem niche has long remained elusive. Early evidence suggested that Paneth cells, a secretory cell type epithelium, functioned as key component niche.1Sato T. et al.Nature. 2011; 469: 415-418Crossref PubMed Scopus (1612) Google Scholar Situated in crypt base, cells intercalate between and express multiple signaling molecules could promote activity. However, subsequent studies have shown are dispensable for maintenance, proliferation, function,2Durand A. al.Proc...
Abstract Unlike many mammalian vital organs, the lung exhibits a robust, multifaceted regenerative response to severe injuries such as influenza infection, which primarily targets epithelial cells in airways and alveoli. Quiescent lung-resident progenitors proliferate, migrate, differentiate following injury, participating two distinct reparative pathways: functionally beneficial regeneration dysplastic tissue remodeling. Intrapulmonary airway-resident basal-like p63 + are one progenitor...
Summary The initiation and progression of cancer are inextricably linked to the tumor microenvironment (TME). Understanding function specific cancer-TME interactions poses a major challenge due in part complexity vivo microenvironment. Here we predict from single cell transcriptomic maps both human colorectal cancers (CRCs) mouse CRC models, ask how these altered established, long-term organoid (tumoroid) cultures, functionally recapitulate myeloid-carcinoma vitro . Tumoroid cultures...
Summary The intestinal epithelium exhibits a rapid and efficient regenerative response to injury. Emerging evidence supports model where plasticity of differentiated cells, particularly those in the secretory lineages, contributes epithelial regeneration upon ablation injury-sensitive stem cells. However, such facultative cell activity is rare within populations. Here we ask whether specific functional properties predict activity. We utilize vivo labeling combined with ex organoid formation...
Abstract Patients with dyskeratosis congenita (DC) and related telomeropathies resulting from premature telomere dysfunction suffer multi-organ failure. In the liver, DC patients present nodular hyperplasia, steatosis, inflammation, cirrhosis. We model liver pathologies using isogenic human induced pluripotent stem (iPS) cells harboring a causal mutation in DKC1 , or clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9-corrected control allele. Differentiation of these iPS...