Rogan A. Grant
A5026696773- Pneumonia and Respiratory Infections
- Neuroinflammation and Neurodegeneration Mechanisms
- Long-Term Effects of COVID-19
- COVID-19 Clinical Research Studies
- Nosocomial Infections in ICU
- Neurogenetic and Muscular Disorders Research
- Mitochondrial Function and Pathology
- Immune cells in cancer
- RNA Research and Splicing
- Genetics, Aging, and Longevity in Model Organisms
- SARS-CoV-2 and COVID-19 Research
- Inhalation and Respiratory Drug Delivery
- Neonatal Respiratory Health Research
- Adipose Tissue and Metabolism
- Amyotrophic Lateral Sclerosis Research
- Medical Imaging and Pathology Studies
- Antibiotic Use and Resistance
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Epigenetics and DNA Methylation
- Extracellular vesicles in disease
- Respiratory viral infections research
- Sepsis Diagnosis and Treatment
- Respiratory Support and Mechanisms
- Endoplasmic Reticulum Stress and Disease
- Spinal Cord Injury Research
Northwestern University
2019-2025
Lung Institute
2023
Children's Hospital of Pittsburgh
2018-2021
University of Pittsburgh Medical Center
2018-2021
Pulmonary and Critical Care Associates
2021
Rice Institute
2019
Rationale: Current guidelines recommend patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia receive empirical antibiotics for suspected bacterial superinfection on the basis of weak evidence. Rates ventilator-associated (VAP) in clinical trials SARS-CoV-2 are unexpectedly low. Objectives: We conducted an observational single-center study to determine prevalence and etiology at time initial intubation incidence subsequent VAP pneumonia. Methods: Bronchoscopic...
Abstract Aging is among the most important risk factors for morbidity and mortality. To contribute toward a molecular understanding of aging, we analyzed age-resolved transcriptomic data from multiple studies. Here, show that transcript length alone explains transcriptional changes observed with aging in mice humans. We present three lines evidence supporting biological importance uncovered transcriptome imbalance. First, vertebrates association primarily displays lower relative abundance...
Mitochondrial electron transport chain (ETC) function modulates macrophage biology; however, mechanisms underlying mitochondria ETC control of immune responses are not fully understood. Here, we report that mutant mice with complex III (CIII)–deficient macrophages exhibit increased susceptibility to influenza A virus (IAV) and LPS-induced endotoxic shock. Cultured bone marrow–derived (BMDMs) isolated from these CIII–deficient released less IL-10 than controls following TLR3 or TLR4...
Traumatic brain injury (TBI) has been predicted to be a predisposing factor for amyotrophic lateral sclerosis (ALS) and other neurological disorders. Despite the importance of TBI in ALS progression, underlying cellular molecular mechanisms are still an enigma. Here, we examined contribution as extrinsic investigated whether influences susceptibility developing neurodegenerative symptoms. To evaluate effects vivo, applied mild severe trauma Drosophila found that leads induction stress...
Significance Disordered epithelial proteostasis is strongly implicated in the pathobiology of pulmonary fibrosis. We found that a small molecule specifically restores protein translation by EIF2B during activation integrated stress response, ISRIB, attenuated severity fibrosis young adult and old mice. Our data support multicellular model which relieving block to differentiation induced response slows recruitment profibrotic monocyte-derived alveolar macrophages attenuate A loss resilience...
Abstract Astrocytes contribute to brain inflammation in neurological disorders but the molecular mechanisms controlling astrocyte reactivity and their relationship neuroinflammatory endpoints are complex poorly understood. In this study, we assessed role of calcium channel, Orai1, for inflammation-evoked depression behaviors mice. Transcriptomics metabolomics analysis indicated that deletion Orai1 astrocytes downregulates genes immunity, metabolism, cell cycle pathways, reduces cellular...
BACKGROUNDDespite guidelines promoting the prevention and aggressive treatment of ventilator-associated pneumonia (VAP), importance VAP as a driver outcomes in mechanically ventilated patients, including patients with severe COVID-19, remains unclear. We aimed to determine contribution unsuccessful mortality for pneumonia.METHODSWe performed single-center, prospective cohort study 585 respiratory failure, 190 whom had who underwent at least 1 bronchoalveolar lavage. A panel intensive care...
BACKGROUNDSurvivors of pneumonia, including SARS-CoV-2 are at increased risk for cognitive dysfunction and dementia. In rodent models, following pneumonia has been linked to the systemic release lung-derived pro-inflammatory cytokines. Microglia poised respond inflammatory signals from circulation, their impairment in murine models dementia humans.METHODSWe measured levels 55 cytokines chemokines bronchoalveolar lavage fluid plasma 341 patients with respiratory failure 13 healthy controls,...
Metformin is among the most prescribed antidiabetic drugs, but primary molecular mechanism by which metformin lowers blood glucose levels unknown. Previous studies have proposed numerous mechanisms acute glucose, including inhibition of mitochondrial complex I electron transport chain (ETC). Here, we used transgenic mice that globally express Saccharomyces cerevisiae internal alternative NADH dehydrogenase (NDI1) protein to determine whether glucose-lowering effect oral administration...
The huntingtin (HTT) protein transports various organelles, including vesicles containing neurotrophic factors, from embryonic development throughout life. To better understand how HTT mediates axonal transport and why this function is disrupted in Huntington's disease (HD), we study vesicle-associated find that it dimethylated at a highly conserved arginine residue (R118) by the methyltransferase 6 (PRMT6). Without R118 methylation, associates less with vesicles, anterograde trafficking...
Abstract Mutations in fused sarcoma (FUS) lead to amyotrophic lateral sclerosis (ALS) with varying ages of onset, progression and severity. This suggests that unknown genetic factors contribute disease pathogenesis. Here we show the identification muscleblind as a novel modifier FUS-mediated neurodegeneration vivo. Muscleblind regulates cytoplasmic mislocalization mutant FUS subsequent accumulation stress granules, dendritic morphology toxicity mammalian neuronal human iPSC-derived neurons....
Epithelial polyploidization after injury is a conserved phenomenon recently shown to improve barrier restoration during wound healing. Whether lung can induce alveolar epithelial polyploidy not known. We show that bleomycin induces type 2 cell (AT2) hypertrophy and polyploidy. AT2 also seen in short term ex vivo cultures, where AT2-to-AT1 transdifferentiation associated with substantial binucleation due failed cytokinesis. Both hypertrophic polyploid features of cells be attenuated by...
Abstract Sarcopenia, which diminishes lifespan and healthspan in the elderly, is commonly exacerbated by viral pneumonia, including influenza COVID-19. In a study of A pneumonia mice, young mice fully recovered from sarcopenia, while older did not. We identified population tissue-resident skeletal muscle macrophages that form spatial niche with satellite cells myofibers but are lost age. Mice gain-of-function mutation Mertk receptor maintained this macrophage-myofiber interaction during...
Abstract Some patients infected with Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) develop severe pneumonia and the acute respiratory distress syndrome (ARDS) [1]. Distinct clinical features in these have led to speculation that immune response virus SARS-CoV-2-infected alveolus differs from other types of [2]. We collected bronchoalveolar lavage fluid samples 86 SARS-CoV-2-induced failure 252 known or suspected pathogens subjected them flow cytometry bulk transcriptomic...
The ability to sense and respond proteotoxic insults declines with age, leaving cells vulnerable chronic acute stressors. Reproductive cues modulate this decline in cellular proteostasis influence organismal stress resilience Caenorhabditis elegans . We previously uncovered a pathway that links the integrity of developing embryos somatic health reproductive adults. Here, we show nuclear receptor NHR-49, an ortholog mammalian peroxisome proliferator-activated α (PPARα), regulates downstream...
Severe community-acquired pneumonia secondary to SARS-CoV-2 is a leading cause of death. Current guidelines recommend patients with receive empirical antibiotic therapy for suspected bacterial superinfection, but little evidence supports these recommendations. We obtained bronchoscopic bronchoalveolar lavage (BAL) samples from requiring mechanical ventilation. analyzed BAL multiplex PCR and quantitative culture determine the prevalence superinfecting pathogens at time intubation identify...
Pathogen clearance and resolution of inflammation in patients with pneumonia require an effective local T cell response. Nevertheless, activation may drive lung injury, particularly during prolonged episodes respiratory failure characteristic severe SARS-CoV-2 pneumonia. While responses the peripheral blood are well described, evolution phenotypes molecular signatures distal caused by or other pathogens is understudied. Accordingly, we serially obtained 432 bronchoalveolar lavage fluid...
Abstract Aging manifests itself through a decline in organismal homeostasis and multitude of cellular physiological functions 1 . Efforts to identify common basis for vertebrate aging face many challenges; example, while there have been documented changes the expression hundreds mRNAs, results across tissues species inconsistent 2 We therefore analyzed age-resolved transcriptomic data from 17 mouse organs 51 human using unsupervised machine learning 3–5 architectural regulatory...
Neurological impairment is the most common finding in patients with post-acute sequelae of COVID-19. Furthermore, survivors pneumonia from any cause have an elevated risk dementia