A5053881319- Linguistics and language evolution
- CRISPR and Genetic Engineering
- Immune Cell Function and Interaction
- Ancient Near East History
- Classical Antiquity Studies
- Lexicography and Language Studies
- Reproductive System and Pregnancy
- CAR-T cell therapy research
- Historical Linguistics and Language Studies
- Immunotherapy and Immune Responses
- Pluripotent Stem Cells Research
- Syntax, Semantics, Linguistic Variation
- Historical, Literary, and Cultural Studies
- Immune Response and Inflammation
- Virus-based gene therapy research
- T-cell and B-cell Immunology
- COVID-19 Impact on Reproduction
- RNA modifications and cancer
- RNA Research and Splicing
- Linguistics and Cultural Studies
- Law, logistics, and international trade
- Epigenetics and DNA Methylation
- Preterm Birth and Chorioamnionitis
- Cancer-related gene regulation
- RNA Interference and Gene Delivery
Harvard University
2014-2025
Beth Israel Deaconess Medical Center
2019-2025
Moscow Research and Clinical Center for Neuropsychiatry
2019
Harvard Stem Cell Institute
2015-2019
Dana-Farber Cancer Institute
2011-2016
Brigham and Women's Hospital
2015
University of Cambridge
2012
University of Münster
2011
University of North Carolina at Pembroke
2001-2007
Leibniz-Forschungsinstitut für Molekulare Pharmakologie
2003-2004
MHC class I plays a critical role in the immune defense against viruses and tumors by presenting antigens to CD8 T cells. An NLR protein, II transactivator (CIITA), is key regulator of gene expression that associates cooperates with transcription factors promoter. Although CIITA also transactivates promoters, loss humans mice results severe reduction only expression, suggesting additional mechanisms regulate I. Here, we identify another member protein family, NLRC5, as transcriptional genes....
How T cells maintain their identity Although best known for pathogen-fighting prowess, lymphocytes also ensure that the immune response does not run amok. A subset of called regulatory (T regs ) performs this function by, example, making sure only attack pathogens and self. can exhibit plasticity in functions face an inflammatory stimulus. Kim et al. sought to identify molecules stable maintenance . Using genetically modified mice, they found both CD4 + CD8 require transcription factor...
Polymorphic HLAs form the primary immune barrier to cell therapy. In addition, innate surveillance impacts engraftment, yet a strategy control both, adaptive and immunity, is lacking. Here we employed multiplex genome editing specifically ablate expression of highly polymorphic HLA-A/-B/-C HLA class II in human pluripotent stem cells. Furthermore, prevent rejection further suppress responses, expressed immunomodulatory factors PD-L1, HLA-G, macrophage "don't-eat me" signal CD47 from AAVS1...
Significance Tumor antigen presentation to CD8 + T cells by MHC class I molecules is crucial for immune responses against cancers, whereas the loss of a common evasion strategy used cancers. However, molecular mechanisms leading deficiency have remained poorly defined. We demonstrate here that transactivator (CITA)/NOD-like receptor (NLR) family, caspase recruitment (CARD) domain containing 5 (NLRC5) major target cancer evasion. Reduced expression and related genes in frequently associated...
Abstract Methods for the targeted integration of genes in mammalian genomes suffer from low programmability, efficiencies or specificities. Here we show that phage-assisted continuous evolution enhances prime-editing-assisted site-specific integrase gene editing (PASSIGE), which couples programmability prime with ability recombinases to precisely integrate large DNA cargoes exceeding 10 kilobases. Evolved and engineered Bxb1 recombinase variants (evoBxb1 eeBxb1) mediated up 60% donor...
Tight regulation of MHC class I gene expression is critical for CD8 T cell activation and host adaptive-immune responses. The promoters genes contain a well-conserved core module, the W/S-X-Y motif, which assembles nucleoprotein complex termed enhanceosome. A member nucleotide-binding domain, leucine-rich repeat (NLR) protein family, NLRC5, newly identified transcriptional regulator genes. NLRC5 associates with transactivates proximal genes, although molecular mechanism transactivation has...
Understanding the root causes of autoimmune diseases is hampered by inability to access relevant human tissues and identify time disease onset. To examine interaction immune cells their cellular targets in type 1 diabetes, we differentiated induced pluripotent stem into pancreatic endocrine cells, including β cells. Here, describe an vitro platform that models features diabetes using stress-induced patient-derived autologous We demonstrate a cell-type-specific response against cell-derived...
Interferon stimulation of cells leads to the tyrosine phosphorylation latent Stat1 and subsequent transient accumulation in nucleus that requires canonical transport factors. However, mechanisms control predominantly cytoplasmic localization unstimulated have not been resolved. We uncovered constitutive energy- factor-independent nucleocytoplasmic shuttling is a property unphosphorylated Stat1, Stat3, Stat5. The NH2- COOH-terminal Stat domains are generally dispensable, whereas alkylation...
Abstract MHC class I and II are crucial for the adaptive immune system. Although regulation of expression by CIITA has long been recognized, mechanism transactivation largely unknown until recent discovery NLRC5/class transactivator. In this study, we show using Nlrc5-deficient mice that NLRC5 is required both constitutive inducible expression. Loss Nlrc5 resulted in severe reduction related genes such as β2-microglobulin, Tap1, or Lmp2, but did not affect levels. IFN-γ stimulation could...
Significance Successful pregnancy poses an immunological paradox, as the mother’s immune system does not reject a fetus, even though it is partially foreign tissue. Fetal extravillous trophoblasts (EVTs) deeply invade uterus and interact with maternal cells without facing rejection. The nonclassical major histocompatibility complex (MHC) molecule HLA-G essential for tolerance induction in pregnancy, yet mechanism by which EVTs uniquely express remains unknown. Using high-throughput cis...
Rationale: Genome-wide association studies have identified genetic loci associated with insulin resistance (IR) but pinpointing the causal genes of a risk locus has been challenging. Objective: To identify candidate for IR, we screened regional and biologically plausible (16 in total) near top 10 IR-loci risk-relevant cell types, namely preadipocytes adipocytes. Methods Results: We generated 16 human Simpson-Golabi-Behmel syndrome preadipocyte knockout lines each single IR-gene knocked out...
Nominal composition is an extremely productive means of word formation in Ancient Greek. Little has been written about it English. Therefore, the present article gives a short introduction to nominal this language general before moving on earliest attested stage language, Mycenaean. An overview compounds Mycenaean Greek given and classification attempted. Thereafter, issues their phonology morphology are discussed both similarities with differences later established. It concluded that...
During pregnancy, fetal extravillous trophoblasts (EVT) play a key role in the regulation of maternal T cell and NK responses. EVT display unique combination human leukocyte antigens (HLA); do not express HLA-A HLA-B, but HLA-C, HLA-E, HLA-G. The mechanisms establishing this HLA expression pattern have been fully elucidated. major histocompatibility complex (MHC) class I II transcriptional activators NLRC5 CIITA are expressed neither by nor model line JEG3, which has an MHC identical to that...
Maternal–fetal immune tolerance guarantees a successful pregnancy throughout gestation. HLA-G, nonclassical human leukocyte antigen (HLA) molecule exclusively expressed in extravillous trophoblasts (EVT), is crucial factor establishing maternal–fetal by interacting with inhibitory receptors on various maternal cells residing the uterus. While trophoblast-specific cis-regulatory elements impacting HLA-G transcription have been described, identity of trans-acting factors controlling expression...
Research on the export of proteins and nucleic acids from nucleus to cytoplasm has greatly gained discovery that actinobacterial toxin leptomycin B (LMB) specifically inactivates receptor chromosomal region maintenance 1 (CRM1). Recently, it was shown myxobacterial cytotoxins, named ratjadones (RATs), also bind CRM1 inhibit nuclear export. However, reaction mechanism RATs not resolved. Here, we show LMB RAT A employ same molecular inactivate CRM1. Alkylation residue Cys528 determines both...
Zika virus (ZIKV) and dengue (DENV) are two closely related flaviviruses that lead to different clinical outcomes. The mechanism for the distinct pathogenesis of ZIKV DENV is poorly understood. Here, we investigate infection macrophages using a human pluripotent stem cell (hPSC)-derived macrophage model discover key virus-specific responses. productively infect hPSC-derived macrophages. DENV, but not ZIKV, strongly activates migration inhibitory factor (MIF) secretion decreases migration....