A5034912242- Erythrocyte Function and Pathophysiology
- Blood properties and coagulation
- Hemoglobinopathies and Related Disorders
- Epigenetics and DNA Methylation
- Immune Response and Inflammation
- Immune cells in cancer
- Acute Myeloid Leukemia Research
- RNA modifications and cancer
- Toxoplasma gondii Research Studies
- Advanced Glycation End Products research
- Blood disorders and treatments
- Vascular Anomalies and Treatments
- Blood groups and transfusion
- Hemoglobin structure and function
- Herpesvirus Infections and Treatments
- Cancer-related gene regulation
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Polyamine Metabolism and Applications
- Immune Cell Function and Interaction
- Single-cell and spatial transcriptomics
- Heme Oxygenase-1 and Carbon Monoxide
- Zebrafish Biomedical Research Applications
- Vascular Malformations and Hemangiomas
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Kruppel-like factors research
Feinstein Institute for Medical Research
2015-2024
Université de Picardie Jules Verne
2023-2024
Institute of Molecular Medicine
2022-2024
Northwell Health
2019-2024
Hématopoïèse et immunologie
2023
Donald & Barbara Zucker School of Medicine at Hofstra/Northwell
2023
Centre National de la Recherche Scientifique
2008-2017
Université de Montpellier
2008-2017
New York Blood Center
2013-2014
Obligate intracellular Apicomplexa parasites share a unique invasion mechanism involving tight interaction between the host cell and parasite surfaces called moving junction (MJ). The MJ, which is anchoring structure for process, formed by secretion of macromolecular complex (RON2/4/5/8), derived from secretory organelles rhoptries, into membrane. AMA1, protein secreted micronemes associated with surface during invasion, has been shown in vitro to bind MJ through direct association RON2....
Significance The biconcave disk shape and deformability of the mammalian RBC are vital to its circulatory function rely upon a 2D viscoelastic spectrin–F-actin network attached membrane. A role for nonmuscle myosin II (NMII) contractility in generating tension this controlling has not been tested. We show that NMIIA forms bipolar filaments RBCs, which associate with F-actin at motor activity regulates interactions control deformability. These results provide previously undescribed mechanism...
Mammalian erythropoiesis occurs within erythroblastic islands (EBIs), niches where maturing erythroblasts interact closely with a central macrophage. While it is generally accepted that EBI macrophages play an important role in erythropoiesis, thorough investigation of the mechanisms by which they support limited largely inability to identify and isolate specific macrophage sub-population constitute EBI. Early studies utilized immunohistochemistry or immunofluorescence study morphology...
Hereditary hemorrhagic telangiectasia (HHT), a genetic bleeding disorder leading to systemic arteriovenous malformations (AVMs), is caused by loss-of-function mutations in the ALK1/ENG/Smad1/5/8 pathway. Evidence suggests that HHT pathogenesis strongly relies on overactivated PI3K/Akt/mTOR and VEGFR2 pathways endothelial cells (ECs). In BMP9/10-immunoblocked (BMP9/10ib) neonatal mouse model of HHT, we report here mTOR inhibitor, sirolimus, receptor tyrosine kinase nintedanib, could...
The metabolic changes controlling the stepwise differentiation of hematopoietic stem and progenitor cells (HSPCs) to mature erythrocytes are poorly understood. Here, we show that HSPC development an erythroid-committed proerythroblast results in augmented glutaminolysis, generating alpha-ketoglutarate (αKG) driving mitochondrial oxidative phosphorylation (OXPHOS). However, sequential late-stage erythropoiesis is dependent on decreasing αKG-driven OXPHOS, find isocitrate dehydrogenase 1...
Hereditary hemorrhagic telangiectasia (HHT) is a highly debilitating and life-threatening genetic vascular disorder arising from endothelial cell (EC) proliferation hypervascularization, for which no cure exists. Because HHT caused by loss-of-function mutations in bone morphogenetic protein 9 (BMP9)-ALK1-Smad1/5/8 signaling, interventions aimed at activating this pathway are of therapeutic value. We interrogated the whole-transcriptome human umbilical vein ECs (HUVECs) found that ALK1...
Abstract Hereditary hemorrhagic telangiectasia (HHT) is a potentially life-threatening genetic vascular disorder caused by loss-of-function mutations in the genes encoding activin receptor-like kinase 1 (ALK1), endoglin, Smad4 and bone morphogenetic protein 9 (BMP9). Injections of mouse neonates with BMP9/10 blocking antibodies lead to HHT-like defects postnatal retinal angiogenesis model. Mothers their newborns share same immunity through transfer maternal during lactation. Here, we...
Identification of stage-specific erythroid cells is critical for studies normal and disordered human erythropoiesis. While immunophenotypic strategies have previously been developed to identify at each stage terminal differentiation, progenitors are currently defined very broadly. Refined characterize BFU-E CFU-E subsets critically needed. To address this unmet need, a flow cytometry-based technique was that combines the established surface markers CD34 CD36 with CD117, CD71, CD105. This...
Patients surviving sepsis develop anemia, but the molecular mechanism is unknown. Here we observed that mice polymicrobial gram-negative hypochromic, microcytic anemia with reticulocytosis. The bone marrow of survivors accumulates polychromatophilic and orthochromatic erythroblasts. Compensatory extramedullary erythropoiesis in spleen defective during terminal differentiation. Circulating tumor necrosis factor (TNF) interleukin (IL)-6 are elevated for 5 d after onset sepsis, serum...
Despite the effective clinical use of steroids for treatment Diamond Blackfan anemia (DBA), mechanisms through which glucocorticoids regulate human erythropoiesis remain poorly understood. We report that sensitivity erythroid differentiation to dexamethasone is dependent on developmental origin CD34+ progenitor cells, specifically increasing expansion progenitors from peripheral blood (PB) but not cord (CB). Dexamethasone erythroid-differentiated PB, CB, resulted in a newly defined...
The protozoan parasite Toxoplasma gondii is equipped with a sophisticated secretory apparatus, including three distinct exocytic organelles, named micronemes, rhoptries, and dense granules. We have dissected the requirements for targeting microneme protein MIC3, key component of T. infection. shown that MIC3 processed in post-Golgi compartment propeptide epidermal growth factor (EGF) modules contain microneme-targeting information. minimal requirement delivery defined by plus any one EGF...
The epithelium is part of an integrated immune system where cytokines, toll-like receptors and their ligands, extracellular vesicles play a crucial role in initiating innate response. IL-36γ pro-inflammatory member the IL-1 family that mainly expressed by epithelial cells, but regulation its expression release are only beginning to be understood. Previous studies reported abundant recurrent respiratory papillomatosis, rare devastating disease caused human papillomaviruses (HPV) types 6 11,...
Genetic ablation of the ferrireductase STEAP3, also known as TSAP6, leads to severe microcytic and hypochromic red cells with moderate anemia in mouse. However, mechanism leading is poorly understood. Previous results indicate that TSAP6/Steap3 a regulator exosome secretion. Using knockout mice, we first undertook comprehensive hematologic characterization cell compartment, confirmed dramatic decrease volume hemoglobin content these erythrocytes. We observed marked anisocytosis well presence...
Abstract Anemic Nan mice carry a mutation (E339D) in the second zinc finger of erythroid transcription factor KLF1. Nan-KLF1 fails to bind subset normal KLF1 targets and ectopically binds large set genes not normally engaged by KLF1, resulting corrupted fetal liver transcriptome. Here, we performed RNAseq using flow cytometric-sorted spleen precursors from adult WT littermates rendered anemic phlebotomy identify global transcriptome changes specific Klf1 as opposed anemia generally. Mutant...
Apicomplexan parasites secrete and inject into the host cell content of specialized secretory organelles called rhoptries, which take part critical processes such as invasion modulation immune response. The rhoptries are structurally functionally divided two compartments. apical duct contains rhoptry neck (RON) proteins that conserved in Apicomplexa involved formation moving junction (MJ) driving parasite invasion. posterior bulb (ROPs) unique to an individual genus and, once injected act...
Abstract Human erythropoiesis is a complex process leading to the production of 2.5 million red blood cells per second. Following commitment hematopoietic stem erythroid lineage, this can be divided into three distinct stages: progenitor differentiation, terminal erythropoiesis, and reticulocyte maturation. We recently resolved heterogeneity progenitors four different subpopulations termed EP1–EP4. Here, we characterized growth factor(s) responsiveness these populations in terms...
During the infection process, Apicomplexa discharge their secretory organelles called micronemes, rhoptries and dense granules to sustain host cell invasion, intracellular replication modulate pathways immune responses. Herein, we describe Toxoplasma gondii Deg-like serine protein (TgDegP), a rhoptry homologous High temperature requirement A (HtrA) or family of proteases. TgDegP undergoes processing in both types I II strains as most proteins. We show that genetic disruption degP gene does...
RASA3 is a Ras GTPase activating protein that plays critical role in blood formation. The autosomal recessive mouse model scat (severe combined anemia and thrombocytopenia) carries missense mutation Rasa3. Homozygotes present with phenotype characteristic of bone marrow failure accompanied by alternating episodes crisis remission. mechanism leading to impaired erythropoiesis peripheral cell destruction as evidenced membrane fragmentation unclear, although we previously reported the...