Jonathan C. Schisler
A5076537324- Mitochondrial Function and Pathology
- Ubiquitin and proteasome pathways
- Metabolism, Diabetes, and Cancer
- Spaceflight effects on biology
- Adipose Tissue and Metabolism
- Pancreatic function and diabetes
- Endoplasmic Reticulum Stress and Disease
- SARS-CoV-2 and COVID-19 Research
- Genetic Neurodegenerative Diseases
- Peroxisome Proliferator-Activated Receptors
- Heat shock proteins research
- Cancer, Hypoxia, and Metabolism
- Muscle Physiology and Disorders
- Peptidase Inhibition and Analysis
- Cardiovascular Function and Risk Factors
- Cardiac Fibrosis and Remodeling
- Cardiomyopathy and Myosin Studies
- Diabetes and associated disorders
- Atherosclerosis and Cardiovascular Diseases
- Receptor Mechanisms and Signaling
- COVID-19 Clinical Research Studies
- Autophagy in Disease and Therapy
- Genetics and Neurodevelopmental Disorders
- Nutrition, Genetics, and Disease
- RNA modifications and cancer
University of North Carolina at Chapel Hill
2016-2025
Emory University
2024
University of North Carolina Health Care
2017
Indiana University School of Medicine
2011-2017
Duke University Hospital
2004-2013
Duke Medical Center
2004-2013
Duke University
2004-2013
University of Freiburg
2012
University of Virginia Medical Center
2005
Joslin Diabetes Center
2005
Ovarian clear-cell carcinoma (OCCC) is an aggressive form of ovarian cancer with high ARID1A mutation rates. Here we present a mutant mouse model OCCC. We find that inactivation not sufficient for tumour formation, but requires concurrent activation the phosphoinositide 3-kinase catalytic subunit, PIK3CA. Remarkably, mice develop highly penetrant tumours OCCC-like histopathology, culminating in haemorrhagic ascites and median survival period 7.5 weeks. Therapeutic treatment pan-PI3K...
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral proteins bind to host mitochondrial proteins, likely inhibiting oxidative phosphorylation (OXPHOS) and stimulating glycolysis. We analyzed gene expression in nasopharyngeal autopsy tissues from patients with disease 2019 (COVID-19). In samples declining titers, the virus blocked transcription of a subset nuclear DNA (nDNA)–encoded OXPHOS genes, induced microRNA 2392, activated HIF-1α induce glycolysis, immune defenses...
It is unclear how severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection leads to the strong but ineffective inflammatory response that characterizes Coronavirus disease 2019 (COVID-19), with amplified immune activation in diverse cell types, including cells without angiotensin-converting enzyme receptors necessary for infection. Proteolytic degradation of SARS-CoV-2 virions a milestone host viral clearance, impact remnant peptide fragments from high loads not known. Here, we...
The large Maf family of basic leucine-zipper–containing transcription factors are known regulators key developmental and functional processes in various cell types, including pancreatic islets. Here, we demonstrate that within the adult pancreas, MafB is only expressed islet α-cells contributes to type–specific expression glucagon gene through activation a conserved control element found between nucleotides −77 −51. was also shown be developing α- β-cells as well proliferating...
Gordon Holmes syndrome (GHS) is a rare Mendelian neurodegenerative disorder characterized by ataxia and hypogonadism. Recently, it was suggested that disordered ubiquitination underlies GHS though the discovery of exome mutations in E3 ligase RNF216 deubiquitinase OTUD4. We performed sequencing family with two three siblings afflicted hypogonadism identified homozygous mutation STUB1 (NM_005861) c.737C→T, p.Thr246Met, gene encodes protein CHIP (C-terminus HSC70-interacting protein). plays...
The laboratory mouse is the most widely used animal model for biomedical research, due in part to its well-annotated genome, wealth of genetic resources, and ability precisely manipulate genome. Despite importance genetics quality control (QC) not standardized, lack cost-effective, informative, robust platforms. Genotyping arrays are standard tools research remain an attractive alternative even era high-throughput whole-genome sequencing. Here, we describe content performance a new iteration...
Highlights•In silico predictions of miR-2392 as a miRNA involved with SARS-CoV-2•Overexpression produces similar biological response COVID-19 infection•miR-2392 is confirmed to circulate in serum and urine patients COVID-19•Development initiated potential antiviral therapeutic against COVID-19SummaryMicroRNAs (miRNAs) are small non-coding RNAs post-transcriptional gene regulation that have major impact on many diseases provide an exciting avenue toward therapeutics. From patient...
The molecular mechanisms underlying the clinical manifestations of coronavirus disease 2019 (COVID-19), and what distinguishes them from common seasonal influenza virus other lung injury states such as acute respiratory distress syndrome, remain poorly understood. To address these challenges, we combine transcriptional profiling 646 nasopharyngeal swabs 39 patient autopsy tissues to define body-wide transcriptome changes in response COVID-19. We then match data with spatial protein...
Abstract Ever-evolving SARS-CoV-2 variants of concern (VOCs) have diminished the effectiveness therapeutic antibodies and vaccines. Developing a coronavirus vaccine that offers greater breadth protection against current future VOCs would eliminate need to reformulate COVID-19 Here, we rationally engineer sequence-conserved S2 subunit spike protein characterize resulting S2-only antigens. Structural studies demonstrate introduction interprotomer disulfide bonds can lock in prefusion trimers,...
Abstract Missions into Deep Space are planned this decade. Yet the health consequences of exposure to microgravity and galactic cosmic radiation (GCR) over years-long missions on indispensable visceral organs such as kidney largely unexplored. We performed biomolecular (epigenomic, transcriptomic, proteomic, epiproteomic, metabolomic, metagenomic), clinical chemistry (electrolytes, endocrinology, biochemistry) morphometry (histology, 3D imaging, miRNA-ISH, tissue weights) analyses using...
We have previously described rat insulinoma INS-1-derived cell lines with robust or poor glucose-stimulated insulin secretion (GSIS). In the current study, we further resolved these into three classes: class 1, glucose-unresponsive/glucagon-expressing; 2, glucose-unresponsive/glucagon-negative; and 3, glucose-responsive/glucagon-negative. The transcription factor Nkx2.2 was expressed relative abundance of 3.3, 1.0, 1.0 in 3 cells, respectively, whereas Nkx6.1 expression had opposite trend:...
The MafA transcription factor is both critical to islet beta-cell function and has a unique pancreatic cell-type-specific expression pattern. To localize the potential transcriptional regulatory region(s) involved in directing beta cell, areas of identity within 5' flanking region mouse, human, rat mafA genes were found between nucleotides -9389 -9194, -8426 -8293, -8118 -7750, -6622 -6441, -6217 -6031, -250 +56 relative start site. species was greater than 75%, with highest bp -7750 (...
Every known SWI/SNF chromatin-remodeling complex incorporates an ARID DNA binding domain-containing subunit. Despite being a ubiquitous component of the complex, physiological roles for this domain remain undefined. Here, we show that disruption ARID1a-DNA in mice results embryonic lethality, with mutant embryos manifesting prominent defects heart and extraembryonic vasculature. The binding-defective ARID1a subunit is stably expressed capable assembling into core catalytic properties, but...
The homeodomain transcription factor Nkx6.1 plays an important role in pancreatic islet β-cell development, but its effects on adult function, survival, and proliferation are not well understood. In the present study, we demonstrated that treatment of primary rat islets with a cytomegalovirus promoter-driven recombinant adenovirus containing cDNA (AdCMV-Nkx6.1) causes dramatic increases [methyl-3H] thymidine 5-bromo-2′-deoxyuridine (BrdU) incorporation number cells per relative to treated...
Muscle ring finger (MuRF)1 is a muscle-specific protein implicated in the regulation of cardiac myocyte size and contractility. MuRF2, closely related family member, redundantly interacts with substrates heterodimerizes MuRF1. Mice lacking either MuRF1 or MuRF2 are phenotypically normal, whereas mice both proteins develop spontaneous skeletal muscle hypertrophy, indicating cooperative control mass by MuRF2. To identify unique role that plays regulating hypertrophy vivo, we created transgenic...
We have identified and validated a spaceflight-associated microRNA (miRNA) signature that is shared by rodents humans in response to simulated, short-duration long-duration spaceflight. Previous studies miRNAs regulate rodent responses spaceflight low-Earth orbit, we confirmed the expression of these proposed reacting simulated conditions. Moreover, astronaut samples from NASA Twins Study signatures miRNA sequencing, single-cell RNA sequencing (scRNA-seq), assay for transposase accessible...
Defects in mitochondrial oxidative phosphorylation (OXPHOS) have been reported COVID-19 patients, but the timing and organs affected vary among reports. Here, we reveal dynamics of through transcription profiles nasopharyngeal autopsy samples from patients infected rodent models. While bioenergetics is repressed viral portal entry, it up regulated lung tissues deceased patients. In most disease stages organs, discrete OXPHOS functions are blocked by virus, this countered host broadly...
The cytokine IFNγ differentially impacts on tumors upon immune checkpoint blockade (ICB). Despite our understanding of downstream signaling events, less is known about regulation its receptor (IFNγ-R1). With an unbiased genome-wide CRISPR/Cas9 screen for critical regulators IFNγ-R1 cell surface abundance, we identify STUB1 as E3 ubiquitin ligase in complex with signal-relaying kinase JAK1. mediates ubiquitination-dependent proteasomal degradation IFNγ-R1/JAK1 through
Human space exploration poses inherent risks to astronauts' health, leading molecular changes that can significantly impact their well-being. These alterations encompass genomic instability, mitochondrial dysfunction, increased inflammation, homeostatic dysregulation, and various epigenomic changes. Remarkably, these bear similarities those observed during the aging process on Earth. However, our understanding of connection between shifts disease development in remains limited. Frailty...
The homeodomain factor Pdx-1 regulates an array of genes in the developing and mature pancreas, but whether regulation each specific gene occurs by a direct mechanism (binding to promoter elements activating basal transcriptional machinery) or indirect (via other genes) is unknown. To determine underlying insulin Pdx-1, we performed kinetic analysis transcription following adenovirus-mediated delivery small interfering RNA for pdx-1 into insulinoma cells pancreatic islets diminish endogenous...