A5044649294- T-cell and B-cell Immunology
- Immune Cell Function and Interaction
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Systemic Lupus Erythematosus Research
- Epigenetics and DNA Methylation
- Cancer-related molecular mechanisms research
- interferon and immune responses
- RNA modifications and cancer
- Renal and related cancers
- Genetic Syndromes and Imprinting
- Genetics and Neurodevelopmental Disorders
- RNA Research and Splicing
- Pluripotent Stem Cells Research
- Hormonal and reproductive studies
- Neonatal Respiratory Health Research
- Animal Genetics and Reproduction
- Respiratory Support and Mechanisms
- Microbial Natural Products and Biosynthesis
- Prenatal Screening and Diagnostics
- Marine Sponges and Natural Products
- CRISPR and Genetic Engineering
- Genomics and Chromatin Dynamics
- Media and Digital Communication
- Neuroscience of respiration and sleep
- Chromosomal and Genetic Variations
University of Pennsylvania
2016-2025
California University of Pennsylvania
2019-2025
California Institute for Regenerative Medicine
2023
Tulane University
2023
Augusta University
2023
Harvard University
2006-2012
Massachusetts General Hospital
2006-2012
Howard Hughes Medical Institute
2006-2012
Scripps Institution of Oceanography
2000
University of California, San Diego
2000
Significance Females have increased immune responsiveness than males, and they are more likely to develop autoimmune disorders. The mechanism underlying these observations is unclear, hypotheses suggest an important role for the X chromosome. Here, we discover that inactive predisposed become partially reactivated in mammalian female lymphocytes, resulting overexpression of immunity-related genes. We also demonstrate lymphocytes from systemic lupus erythematosus patients different epigenetic...
Systemic lupus erythematosus (SLE) is an autoimmune disorder that predominantly affects women and driven by autoreactive T cell–mediated inflammation. It known individuals with multiple X-chromosomes are at increased risk for developing SLE; however, the mechanisms underlying this genetic basis unclear. Here, we use single cell imaging to determine epigenetic features of inactive X (Xi) in thymocytes, mature subsets, cells from SLE patients mice. We show Xist RNA heterochromatin...
The Tsx gene resides at the X-inactivation center and is thought to encode a protein expressed in testis, but its function has remained mysterious. Given proximity noncoding genes that regulate X-inactivation, here we characterize determine mice. We find actually long transcript robustly meiotic germ cells, embryonic stem brain. Targeted deletion of generates viable offspring only mildly affected cells. However, mutant cells are severely growth-retarded, differentiate poorly, show elevated...
Significance Pathogenic autoantibodies are a feature of systemic lupus erythematosus (SLE), which 85% patients women. Multiple X chromosomes increase the risk for SLE, suggesting an important role X-linked gene expression female sex bias. X-chromosome inactivation (XCI) regulates on inactive X. This study examines XCI maintenance across multiple human B cell subsets from healthy individuals and SLE patients. Importantly, we found that both pediatric adult patient cells have significant...
Polycomb group proteins mediate transcriptional silencing in diverse developmental processes. Sex chromosomes undergo chromosome-wide transcription during male meiosis. Here we report that mouse SCML2 (Sex comb on midleg-like 2), an X chromosome-encoded polycomb protein, is specifically expressed germ cells, including spermatogonia, spermatocytes, and round spermatids. associates with phosphorylated H2AX localizes to the XY body spermatocytes. Loss of mice causes defective spermatogenesis,...
Systemic lupus erythematosus (SLE) is a highly female-biased systemic autoimmune disease, but the molecular basis for this female bias remains incompletely elucidated. B and T lymphocytes from patients with SLE mouse models of exhibit features epigenetic dysregulation on X chromosome which may contribute to strong bias. We therefore examined fidelity dynamic X-chromosome inactivation maintenance (dXCIm) in pathogenesis two murine spontaneous lupus-NZM2328 MRL/lpr-with disparate levels...
Systemic lupus erythematosus (SLE) is an autoimmune disease preferentially observed in females. X-linked gene expression XX females normalized to that of XY males by X-Chromosome Inactivation (XCI). However, B cells from female SLE patients and mouse models exhibit mislocalization Xist RNA, a critical regulator XCI, aberrant genes, suggesting impairment XCI may contribute disease. Here, we find subset mice harboring conditional deletion
The transcriptional programs that regulate CD8 T-cell differentiation and function in the context of viral infections or tumor immune surveillance have been extensively studied; yet how long noncoding RNAs (lncRNAs) loci transcribe them contribute to regulation T cells during remains largely unexplored. Here, we report transcription lncRNA Morrbid is specifically induced by receptor (TCR) type I IFN stimulation early stages acute chronic lymphocytic choriomeningitis virus (LCMV) infection....
In females, the long noncoding RNA Xist drives X-chromosome Inactivation (XCI) to equalize X-linked gene dosage between sexes. Unlike other somatic cells, dynamic regulation of and heterochromatin marks on inactive X (Xi) in female lymphocytes results biallelic expression some genes, including Tlr7, Cxcr3, Cd40l, implicated sex-biased autoimmune diseases. We now find that while is dispersed across nucleus NK cells dendritic (DCs) partially co-localizes with H3K27me3 bone marrow-derived...
Three new oxepin-containing natural products (1–3) and two fumiquinazoline metabolites (4–5) have been isolated from organic extracts of the culture broth mycelia an Acremonium sp., a fungus obtained surface Caribbean tunicate Ecteinascidia turbinata. The structures five compounds were determined through extensive analysis 1D- 2D-NMR data, mass spectrometry. Compound 1 exhibited good anti-inflammatory activity in topical RTX-induced mouse ear edema assay. Compounds 4 5 weak antifungal toward...
X chromosome inactivation (XCI) balances X-linked gene dosage between sexes. Unstimulated T cells lack cytological enrichment of X-inactive specific transcript (Xist) RNA and heterochromatic modifications on the inactive (Xi), which are involved in maintenance XCI, these return to Xi after stimulation. Here, we examined allele-specific expression epigenomic profiles cells. We found that unstimulated is largely compensated enriched with repressive H3K27me3 modification but not...
X-Chromosome Inactivation (XCI) involves epigenetic pathways to equalize X-linked gene expression between female and male mammals. XCI is dynamic in B cells, as cytological enrichment of Xist RNA heterochromatic marks on the inactive X-chromosome (Xi) are absent naïve cells yet return following mitogenic stimulation. Here, we asked whether any histone present Xi required for their deposition retention We find that depleted H2AK119Ub H3K9me3 but enriched DNA methylation H3K27me3, which...
SUMMARY X Chromosome Inactivation (XCI) equalizes X-linked gene expression between sexes. B cells exhibit dynamic XCI, with Xist RNA/heterochromatic marks absent on the inactive (Xi) in naive but returning following mitogenic stimulation. The impact of XCI Xi structure and maintenance was previously unknown. Here, we find dosage compensation state-specific escape genes vitro activated cells. Allele-specific OligoPaints indicate similar Xa territories that are less compact than fibroblasts....
Purpose and Appropriate Sample Types This 30-color panel was developed to enable the enumeration purification of distinct circulating immune cell subsets implicated in pathogenesis systemic autoimmune diseases including rheumatoid arthritis (RA), lupus erythematosus (SLE), sclerosis (SSc; scleroderma), Sjögren’s disease (SjD), idiopathic inflammatory myopathy (IIM), others. While designed for application peripheral blood mononuclear cells, inclusion CD45 coupled with ability extract cellular...
Sex differences exist for many lung pathologies, including COVID-19 and pulmonary fibrosis, but the mechanistic basis this remains unclear. Alveolar type 2 cells (AT2s), which play a key role in alveolar regeneration, express X-linked Ace2 gene that has roles repair SARS-CoV-2 pathogenesis, suggesting X chromosome inactivation (XCI) AT2s might impact sex-biased pathology. Here we investigate XCI maintenance sex-specific expression profiles using male female AT2s. Remarkably, inactive (Xi)...
Long noncoding RNAs (lncRNAs) can regulate gene expression in a cell-specific fashion during development. Here, we identify novel lncRNA from the X chromosome that named lncRHOXF1 and which is abundantly expressed trophectoderm primitive endoderm cells of human blastocyst-stage embryos. spliced polyadenylated about 1 kb length found both nuclear cytoplasmic compartments vitro differentiated progenitor cells. Gain-of-function experiments embryonic stem cells, normally lack RNA, revealed...
Abstract Background Sex hormones and sex chromosomes play a vital role in cardiovascular disease. Testosterone plays crucial men’s health. Lower testosterone level is associated with cardiometabolic diseases, including inflammation, atherosclerosis, type 2 diabetes. replacement beneficial or neutral to deficiency events. supplementation hypogonadal men improves libido, increases muscle strength, enhances mood. We hypothesized that (XX XY) interaction arterial stiffening. Methods used four...
The placenta is a short-lived tissue required for embryonic growth and survival, it fetal derived. Fetal sex influences gestation, many sexual dimorphic diseases have origins in utero. There sex-biased gene expression third-trimester human placentas, yet the origin of sex-specific unknown. Here, we used an vitro differentiation model to convert stem cells (hESCs) into trophoblastic progenitor first-trimester placenta, which will eventually become mature extravillous trophoblasts...