A5054072160- Neonatal Respiratory Health Research
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Congenital Diaphragmatic Hernia Studies
- Tracheal and airway disorders
- Endoplasmic Reticulum Stress and Disease
- Congenital heart defects research
- Galectins and Cancer Biology
- Microtubule and mitosis dynamics
- Tumors and Oncological Cases
- PI3K/AKT/mTOR signaling in cancer
- Hippo pathway signaling and YAP/TAZ
- Peptidase Inhibition and Analysis
- Medical Imaging and Pathology Studies
- Tissue Engineering and Regenerative Medicine
- Bioinformatics and Genomic Networks
- Inhalation and Respiratory Drug Delivery
- Pluripotent Stem Cells Research
- Cancer, Hypoxia, and Metabolism
- Protein Tyrosine Phosphatases
- Phagocytosis and Immune Regulation
- Enzyme Structure and Function
- Ubiquitin and proteasome pathways
- Polyamine Metabolism and Applications
- Cardiovascular and Diving-Related Complications
- Neurogenesis and neuroplasticity mechanisms
Icahn School of Medicine at Mount Sinai
2024-2025
University of California, San Francisco
2020-2023
University of California System
2021
University of California San Francisco Medical Center
2019
Cardiovascular Institute Hospital
2019
University of South Florida
2014-2017
University of Tampa
2014
University of California, Irvine
2012
Abstract The cell type specific sequences of transcriptional programs during lung regeneration have remained elusive. Using time-series single RNA-seq the bleomycin injury model, we resolved dynamics for 28 types. Trajectory modeling together with lineage tracing revealed that airway and alveolar stem cells converge on a unique Krt8 + transitional state regeneration. These squamous morphology, feature p53 NFkB activation display features cellular senescence. Krt8+ appears in several...
Choroid plexus epithelial cells (CPECs) have essential developmental and homeostatic roles related to the CSF blood–CSF barrier they produce. Accordingly, CPEC dysfunction has been implicated in many neurological disorders, such as Alzheimer's disease, transplant studies provided proof-of-concept for CPEC-based therapies. However, therapies hindered by inability expand or generate CPECs culture. During development, differentiate from preneurogenic neuroepithelial require bone morphogenetic...
Abstract Idiopathic pulmonary fibrosis (IPF) is characterized by lung remodeling arising from epithelial injury, aberrant fibroblast growth, and excessive deposition of extracellular matrix. Repeated injury elicits abnormal wound repair remodeling, often associated with alveolar collapse edema, leading to focal hypoxia. Here, we demonstrate that hypoxia a physiological insult contributes (PF) define its molecular roles in profibrotic activation cells. Hypoxia increased transcription genes...
Loss of the liquid layer that lines lung's air-facing surface underpins mechanisms major lung diseases, but development therapies restore secretion is hampered by an incomplete understanding cell types drive it. Here, we show CFTR function in alveolar type 1 (AT1) cells - a comprises 95% presumed to be unimportant CFTR-related diseases critical and secretion-mediated clearance particles S. aureus from alveoli. Our findings reveal essential roles for AT1 homeostasis defense, they call...
PTEN phosphorylation at its C-terminal (C-tail) serine/threonine cluster negatively regulates tumor suppressor function. However, the consequence of such inhibition and downstream effects in driving lung cancer remain unexplored. Herein, we ascertain molecular mechanisms by which compromises function, contributing to cancer. Replacement residues with alanine generated PTEN-4A, a phosphorylation-deficient mutant, suppressed cell proliferation migration. PTEN-4A preferentially localized...
Lung injury activates quiescent stem and progenitor cells to regenerate alveolar structures. The sequence coordination of transcriptional programs during this process has largely remained elusive. Using single cell RNA-seq, we first generated a whole-organ bird’s-eye view on cellular dynamics cell-cell communication networks mouse lung regeneration from ∼30,000 at six timepoints. We discovered an injury-specific state characterized by Krt8 in flat epithelial covering surfaces. number these...
We reveal presence of intrinsically disordered regions in human kinome and build a kinase–kinase interaction network identifying novel SRC–SMAD relationship.
SUMMARY Understanding differential lineage potential of orthologous stem cells across species can shed light on human disease. Here, utilizing 3D organoids, single cell RNAseq, and xenotransplants, we demonstrate that alveolar type 2 (hAEC2s), unlike murine AEC2s, are multipotent able to transdifferentiate into KRT5+ basal when co-cultured with primary fibroblasts in organoids. Trajectory analyses immunophenotyping epithelial progenitors idiopathic pulmonary fibrosis (IPF) indicate hAEC2s...
BCL-2 family members are known to be implicated in survival numerous biological settings. Here, we provide evidence that injury and repair processes lungs, mainly acts attenuate endoplasmic reticulum (ER) stress limit extracellular matrix accumulation. Days after an intratracheal bleomycin challenge, mice lose a fraction of their alveolar type II epithelium from terminal ER driven by activation the critical sensor effector IRE1α. This is dramatically increased inhibition, because IRE1α...
Abstract Organ fibrosis is often accompanied by aberrant epithelial reprogramming, culminating in a transformed barrier composed of scar and metaplastic epithelium. Understanding how the promotes an abnormal response could better inform strategies to reverse fibrotic damage. Here we show that Gli1 + mesenchymal stromal cells (MSCs), previously shown contribute myofibroblasts scar, promote differentiation airway progenitors into KRT5+ basal vitro vivo . During repair, MSCs integrate hedgehog...
We present data on the evolution of intrinsically disordered regions (IDRs) taking into account entire human protein kinome. The evolutionary IDRs with respect to kinase domains (KDs) and kinases as a whole (WP) are reported. Further, we have reported its post translational modifications FAK1 their contribution cytoskeletal remodeling. also report build protein-protein interaction (PPI) network primary secondary FAK1-interacting hybrid proteins. Detailed analysis effect FAK1-related...
Abstract Idiopathic pulmonary fibrosis (IPF) is a disease of progressive interstitial fibrosis, which leads to severe debilitation, respiratory failure, and death. In IPF, environmental exposures interact with genetic risk factors engender critical patho-etiological events in lung epithelial cells, including endoplasmic reticulum (ER) stress TGFβ signaling, but the interactions between these disparate pathways are not well understood. We previously showed that kinase inhibitors IRE1α...