A5080557372- Extracellular vesicles in disease
- Transplantation: Methods and Outcomes
- Immune Cell Function and Interaction
- Reproductive Biology and Fertility
- CAR-T cell therapy research
- Immune cells in cancer
- RNA Interference and Gene Delivery
- Immunotherapy and Immune Responses
- MicroRNA in disease regulation
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Immune Response and Inflammation
- Cancer Immunotherapy and Biomarkers
- T-cell and B-cell Immunology
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Diabetes and associated disorders
- SARS-CoV-2 and COVID-19 Research
- Ovarian function and disorders
- Circular RNAs in diseases
- Sirtuins and Resveratrol in Medicine
- Neonatal Respiratory Health Research
- COVID-19 Clinical Research Studies
- Adipose Tissue and Metabolism
- Obstructive Sleep Apnea Research
- Cancer Cells and Metastasis
- Virus-based gene therapy research
University of Chicago Medical Center
2021-2023
Universal Scientific Education and Research Network
2021-2023
Northwestern University
2017-2023
Research Network (United States)
2022-2023
Thoracic Surgery Foundation
2020-2021
Education and Research Network
2021
University of Chicago
2016-2017
SleepMed
2017
Comer Children's Hospital
2017
The San Raffaele Telethon Institute for Gene Therapy
2013-2015
The contributions of diverse cell populations in the human lung to pulmonary fibrosis pathogenesis are poorly understood. Single-cell RNA sequencing can reveal changes within individual during that important for disease pathogenesis.
Since the first publications coining term RNA-seq (RNA sequencing) appeared in 2008, number of containing data has grown exponentially, hitting an all-time high 2,808 2016 (PubMed). With this wealth being generated, it is a challenge to extract maximal meaning from these datasets, and without appropriate skills background, there risk misinterpretation data. However, general understanding principles underlying each step analysis allows investigators background programming bioinformatics...
Donor nonclassical monocytes mediate primary lung allograft dysfunction by recruiting neutrophils via MyD88-dependent production of CXCL2.
Ischemia-reperfusion injury, a form of sterile inflammation, is the leading risk factor for both short-term mortality following pulmonary transplantation and chronic lung allograft dysfunction. While it well recognized that neutrophils are critical mediators acute processes guide their entry into tissue not understood. Here, we found CCR2+ classical monocytes necessary sufficient mediating extravasation during ischemia-reperfusion injury hilar clamping or transplantation. The were mobilized...
Tregs require Foxp3 expression and induction of a specific DNA hypomethylation signature during development, after which persist as self-renewing population that regulates immune system activation. Whether maintenance methylation is required for Treg lineage development stability how patterns are maintained self-renewal remain unclear. Here, we demonstrate the epigenetic regulator ubiquitin-like with plant homeodomain RING finger domains 1 (Uhrf1) essential methyl-DNA marks stabilize...
Primary graft dysfunction (PGD) is the predominant cause of early loss following lung transplantation. We recently demonstrated that donor pulmonary intravascular nonclassical monocytes (NCM) initiate neutrophil recruitment. Simultaneously, host-origin classical (CM) permeabilize vascular endothelium to allow extravasation necessary for PGD. Here, we show a CCL2-CCR2 axis CM Surprisingly, although intravital imaging and multichannel flow cytometry revealed depletion NCM abrogated...
Hepatocyte-targeted InsB 9–23 gene transfer protects from type 1 diabetes by inducing antigen-specific regulatory T cells.
Abstract Obstructive sleep apnea (OSA) affects 8–10% of the population, is characterized by chronic intermittent hypoxia (CIH), and causally associates with cardiovascular morbidities. In CIH-exposed mice, closely mimicking chronicity human OSA, increased accumulation proliferation pro-inflammatory metabolic M1-like macrophages highly expressing CD36, emerged in aorta. Transcriptomic MeDIP-seq approaches identified activation pro-atherogenic pathways involving a complex interplay histone...
Chronic sleep fragmentation (SF) increases cancer aggressiveness in mice. Exosomes exhibit pleiotropic biological functions, including immune regulatory antigen presentation, intracellular communication and inter-cellular transfer of RNA proteins. We hypothesized that SF-induced alterations biosynthesis cargo plasma exosomes may affect tumor cell properties.SF-derived increased proliferation (~13%), migration (~2.3-fold) extravasation (~10%) when compared to from SC-exposed Similarly, Pre...
Sleep is an important modulator of metabolic function. Disruptions sleep in circadian rhythm are common modern societies and associated with increased risk developing cardiometabolic disorders. Exosomes ubiquitous extracellular vesicles that may play a mechanistic role derangements. We hypothesized alternating dark-light cycles mimicking shift work mice would alter fecal microbiota colonic epithelium permeability plasma exosome cargo C57BL/6 were randomly assigned to (i) control day light...
Increased visceral white adipose tissue (vWAT) mass results in infiltration of inflammatory macrophages that drive inflammation and insulin resistance. Patients with obstructive sleep apnea (OSA) suffer from increased prevalence obesity, resistance, metabolic syndrome. Murine models intermittent hypoxia (IH) mimicking moderate-severe OSA manifest resistance following short-term IH. We examined mice the effect long-term IH on cellular changes within vWAT potential normoxic recovery...
The processes underlying synchronous multiple organ fibrosis in systemic sclerosis (SSc) remain poorly understood. Age-related pathologies are associated with organismal decline nicotinamide adenine dinucleotide (NAD+) that is due to dysregulation of NAD+ homeostasis and involves the NADase CD38. We now show CD38 upregulated patients diffuse cutaneous SSc, levels skin associate molecular signatures, as well clinical scores, while expression key NAD+-synthesizing enzymes unaltered. Boosting...
A major complication of factor replacement therapy for haemophilia is the development anti‐factor neutralizing antibodies (inhibitors). Here we show that liver gene by lentiviral vectors (LVs) expressing IX (FIX) strongly reduces pre‐existing anti‐FIX and eradicates FIX inhibitors in B mice. Concomitantly, plasma levels clotting activity rose to 50–100% normal. The treatment was effective 75% treated FIX‐specific cells (PCs) memory were reduced, likely because B‐cell depletion response...
Sickle cell anaemia (SCA) is the most frequent genetic haemoglobinopathy, which exhibits a highly variable clinical course characterized by hyper-coagulable and pro-inflammatory states, as well endothelial dysfunction. Extracellular microvesicles are released into biological fluids play role in modifying functional phenotype of target cells. We hypothesized that potential differences plasma-derived extracellular (EV) function cargo from SCA patients may underlie divergent trajectories....
The presence of obstructive sleep apnea (OSA) in patients with cancer appears to be accompanied by poorer outcomes. However, the mechanisms underlying such association are unknown. Tumor infiltrating lymphocytes (TILs), including CD8+ T cells, function as cytotoxic (CTLs) and mount immune responses release cytolytic enzymes, granzyme B (GzmB), perforin (Prf), cytokines interferon (IFN)-γ.Using established vivo mouse models, we investigated cells stem (CSCs) intermittent hypoxia (IH)...
Despite the widespread use of antibiotics, bacterial pneumonias in donors strongly predispose to fatal syndrome primary graft dysfunction (PGD) following lung transplantation. We report that endotoxin persists human donor lungs after pathogen is cleared with antibiotics and associated neutrophil infiltration PGD. In mouse models, depletion tissue-resident alveolar macrophages (TRAMs) attenuated recruitment response as shown by compartmental staining intravital imaging. Bone marrow chimeric...
Intermittent hypoxia (IH) induces activation of the integrated stress response (ISR), but its role in IH-induced visceral white adipose tissue (vWAT) insulin resistance is unknown. CHOP activated by chronic ISR, whereas GADD34 dephosphorylates subunit translation initiation factor 2 (eIF2α), leading to termination ISR. We hypothesized that CHOP/Gadd34 null mice would not manifest evidence after IH exposures. Eight-week-old CHOP/GADD34-/- (double mutant [DM]) and wild-type (WT) littermates...
Delayed lung repair leads to alveolopleural fistulae, which are a major cause of morbidity after resections. We have reported that intrapleural hypercapnia is associated with delayed resection. Here, we provide new evidence delays wound closure both large airway and alveolar epithelial cell monolayers because inhibition migration. Cell migration were dependent on Rac1-GTPase activation, was suppressed by directly through the upregulation AMP kinase indirectly injury-induced NF-κB-mediated...
Sleep fragmentation (SF) is highly prevalent and has emerged as an important contributing factor to obesity metabolic syndrome. We hypothesized that SF-induced increases in protein tyrosine phosphatase-1B (PTP-1B) expression activity underlie increased food intake, inflammation, leptin insulin resistance.Wild-type (WT) ObR-PTP-1b-/- mice (Tg) were exposed SF control sleep (SC), intake was monitored. WT received a PTP-1B inhibitor (RO-7d; Tx) or vehicle (Veh). Upon completion of exposures,...