A5036234028- Osteoarthritis Treatment and Mechanisms
- RNA Research and Splicing
- Neuroinflammation and Neurodegeneration Mechanisms
- Dermatology and Skin Diseases
- Knee injuries and reconstruction techniques
- Neuroendocrine regulation and behavior
- Cardiac Fibrosis and Remodeling
- Bone Metabolism and Diseases
- RNA regulation and disease
- Molecular Biology Techniques and Applications
- Epigenetics and DNA Methylation
- Cancer-related molecular mechanisms research
- Stress Responses and Cortisol
- MicroRNA in disease regulation
- Helicobacter pylori-related gastroenterology studies
- Endoplasmic Reticulum Stress and Disease
- Phagocytosis and Immune Regulation
- Maternal Mental Health During Pregnancy and Postpartum
- Circadian rhythm and melatonin
- Immune cells in cancer
- Mosquito-borne diseases and control
- Infant Health and Development
- Asthma and respiratory diseases
- Single-cell and spatial transcriptomics
- Autophagy in Disease and Therapy
Washington University in St. Louis
2016-2025
James S. McDonnell Foundation
2019-2025
Seattle University
2021
National Human Genome Research Institute
2019-2020
Barnes-Jewish Hospital
2017-2018
Jewish Hospital
2017
Glioblastoma is a highly lethal brain cancer that frequently recurs in proximity to the original resection cavity. We explored use of oncolytic virus therapy against glioblastoma with Zika (ZIKV), flavivirus induces cell death and differentiation neural precursor cells developing fetus. ZIKV preferentially infected killed stem (GSCs) relative differentiated tumor progeny or normal neuronal cells. The effects GSCs were not general property neurotropic flaviviruses, as West Nile...
Sleep loss is associated with cognitive decline in the aging population and a risk factor for Alzheimer’s disease (AD). Considering crucial role of immunomodulating genes such as that encoding triggering receptor expressed on myeloid cells type 2 (TREM2) removing pathogenic amyloid-β (Aβ) plaques regulating neurodegeneration brain, our aim was to investigate whether how sleep influences microglial function mice. We chronically sleep-deprived wild-type mice 5xFAD mouse model cerebral...
Worldwide, ∼196 million are afflicted with endometriosis, a painful disease in which endometrial tissue implants and proliferates on abdominal peritoneal surfaces. Theories the origin of endometriosis remained inconclusive. Whereas up to 90% women experience retrograde menstruation, only 10% develop suggesting that factors alter environment might contribute endometriosis. Herein, we report whereas some gut bacteria promote others protect against by fermenting fiber produce short-chain fatty...
Alzheimer’s disease (AD) is the most prevalent neurodegenerative disorder. Antiamyloid antibody treatments modestly slow progression in mild dementia due to AD. Emerging evidence shows that homeostatic dysregulation of brain immune system, especially orchestrated by microglia, plays an important role onset and progression. Thus, a major question how modulate phenotype function microglia treat Xenon (Xe) gas noble used human patients as anesthetic neuroprotectant for treating injuries. Xe...
ABSTRACT Microarrays and RNA‐seq are at the forefront of high throughput transcriptome analyses. Since these methodologies based on different principles, there concerns about concordance data between two techniques. The microarrays for genome‐wide analysis differential gene expression has not been rigorously assessed in clinically derived ligament tissues. To demonstrate to assess potential benefits over microarrays, we differences transcript anterior cruciate (ACL) tissues time‐from‐injury....
Abstract Misfolded protein aggregates may cause toxic proteinopathy, including autosomal dominant tubulointerstitial kidney disease due to uromodulin mutations (ADTKD- UMOD ), a leading hereditary disease. There are no targeted therapies. In our generated mouse model recapitulating human ADTKD- carrying mutation, we show that autophagy/mitophagy and mitochondrial biogenesis impaired, cGAS-STING activation tubular injury. Moreover, demonstrate inducible overexpression of mesencephalic...
Abstract Background Sex differences in the brain may play an important role sex-differential prevalence of neuropsychiatric conditions. Methods In order to understand transcriptional basis sex differences, we analyzed multiple, large-scale, human postmortem RNA-Seq datasets using both within-region and pan-regional frameworks. Results We find evidence sex-biased transcription many autosomal genes, some which provide for pathways cell population between chromosomally male female individuals....
Abstract Although endometrial cancer is the most common of female reproductive tract, we have little understanding what controls beyond transcriptional effects steroid hormones such as estrogen. As a result, limited therapeutic options for ~62,000 women diagnosed with each year in United States. Here, an attempt to identify new prognostic and targets, focused on area this cancer—alternative mRNA splicing—and investigated whether splicing factor, SF3B1, plays important role pathogenesis....
Stem cell systems are essential for the development and maintenance of polarized tissues. Intercellular signaling pathways control stem systems, where niche cells signal to maintain fate/self-renewal inhibit differentiation. In C. elegans germline, GLP-1 Notch specifies fate, employing sequence-specific DNA binding protein LAG-1 implement transcriptional response. We undertook a comprehensive genome-wide approach identify targets signaling. expected primary response target genes be evident...
Itch is an unpleasant sensation that elicits robust scratching and aversive experience. However, the identity of cells neural circuits organize this information remains elusive. Here, we show necessity sufficiency chloroquine-activated neurons in central amygdala (CeA) for both itch associated aversion. Further, CeA play important roles itch-related comorbidities, including anxiety-like behaviors, but not some appetitive behaviors previously ascribed to neurons. RNA-sequencing identified...
Abstract Background Elevated levels of periostin (Postn) in the cartilage and bone are associated with osteoarthritis (OA). However, it remains unknown whether Postn loss-of-function can delay or prevent development OA. In this study, we sought to better understand role OA assessed functional impact deficiency on post-traumatic age-related mice. Methods The effects were studied two murine experimental models using −/− ( n = 32) littermate wild-type wt ) mice 36). Post-traumatic was induced...
Treatment of osteoporosis commonly diminishes osteoclast number which suppresses bone formation thus compromising fracture prevention. Bone is not suppressed, however, when degradation reduced by retarding functional resorptive capacity, rather than differentiation. We find deletion deubiquitinase, BRCA1-associated protein 1 (Bap1), in myeloid cells (Bap1
Anterior cruciate ligament (ACL) tears are a common injury. The healing potential of the injured ACL is poorly understood and considered limited. Therefore, most that treated surgically undergo reconstruction rather than repair. However, there has been renewed interest recently in repairing despite unanswered questions regarding capacity ACL.Gene expression varies with time from injury.Descriptive laboratory study.Transcriptome-wide profiles 24 human remnants recovered at surgical were...
Significance Neutrophils are essential for host defense against pathogens. Although calcium signals direct numerous cell functions, the molecular machinery that orchestrates influx into neutrophils is poorly defined. We demonstrate ORAI1 and ORAI2 key components of mouse neutrophil release-activated channel bactericidal function. find separate two populations with distinct regulation membrane potential during influx, which influences magnitude SOCE effect ORAI isoform deficiency. These...
Abstract Quaking RNA binding protein (QKI) is essential for oligodendrocyte development as myelination requires myelin basic mRNA regulation and localization by the cytoplasmic isoforms (e.g., QKI-6). QKI-6 also highly expressed in astrocytes, which were recently demonstrated to have regulated localization. Here, we define targets of QKI mouse brain via CLIPseq show that binds 3′UTRs a subset astrocytic mRNAs. Binding enriched near stop codons, mediated partially QKI-binding motifs (QBMs),...
Significance The Rab5 GTPase functions in early endosome (EE) fusion the endocytic pathway. Here, we propose that RAB5B also has a noncanonical vesicular function regulated secretion pathway produces mature surfactant proteins SP-B and SP-C lung. This was revealed from investigation of proband with interstitial lung disease suggestive dysfunction disorder who carried de novo Asp136His variant gene. Our modeling C. elegans provided information on genetic cell biological mechanism, analyses...
Periostin (POSTN), a secretory matricellular matrix protein, plays multitude of biologic functions. Various splice variants POSTN have been described; however, their expression pattern and functional implications are not completely understood. This study was undertaken to decipher the differential its in various tissues cell types. We show that more highly expressed anterior cruciate ligament (ACL) remnants compared with articular cartilage at cellular tissue level. Isoforms 1 8 were only...