A5005196958- Viral-associated cancers and disorders
- Lymphoma Diagnosis and Treatment
- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Chronic Lymphocytic Leukemia Research
- Immunotherapy and Immune Responses
- Polyomavirus and related diseases
- Renal Diseases and Glomerulopathies
- Hematopoietic Stem Cell Transplantation
- Single-cell and spatial transcriptomics
- CAR-T cell therapy research
- CNS Lymphoma Diagnosis and Treatment
- IL-33, ST2, and ILC Pathways
- Eosinophilic Disorders and Syndromes
- Proteoglycans and glycosaminoglycans research
- Glycosylation and Glycoproteins Research
- Telomeres, Telomerase, and Senescence
- Amyloidosis: Diagnosis, Treatment, Outcomes
- Kawasaki Disease and Coronary Complications
- Immune cells in cancer
- Fibroblast Growth Factor Research
- Acute Lymphoblastic Leukemia research
- Histiocytic Disorders and Treatments
- Angiogenesis and VEGF in Cancer
- Multiple Myeloma Research and Treatments
University of Pennsylvania
2019-2025
Cancer Research Institute
2019-2021
Duke Medical Center
2014-2017
Duke University
2011
Abstract Castleman disease (CD) includes a group of rare and heterogeneous disorders with characteristic lymph node histopathological abnormalities. CD can occur in single station, which is referred to as unicentric (UCD). also involve multicentric lymphadenopathy inflammatory symptoms (multicentric [MCD]). MCD human herpesvirus-8 (HHV-8)–associated MCD, POEMS-associated HHV-8−/idiopathic (iMCD). The first-ever diagnostic treatment guidelines were recently developed for iMCD by an...
Abstract Fibroblastic reticular cells (FRCs) direct the interaction and activation of immune in discrete microenvironments lymphoid organs. Despite their important role steering innate adaptive immunity, age- inflammation-associated changes molecular identity functional properties human FRCs have remained largely unknown. Here, we show that tonsillar undergo dynamic reprogramming during life respond vigorously to inflammatory perturbation comparison other stromal cell types. The peptidase...
Idiopathic multicentric Castleman disease (iMCD) is a rare hematologic disorder with heterogeneous presentations ranging from moderate constitutional symptoms to life-threatening multiorgan system involvement. iMCD patients present vastly different clinical subtypes, some demonstrating thrombocytopenia, anasarca, fever/elevated C-reactive protein, reticulin fibrosis/renal failure, and organomegaly (TAFRO) others more mild/moderate potential for severe (not otherwise specified, NOS). Due its...
Heparan sulfate (HS) is an essential component of the extracellular matrix (ECM), which serves as a barrier to tumor invasion and metastasis. Heparanase promotes growth by cleaving HS chains proteoglycan releasing HS-bound angiogenic factors facilitates metastasis degrading ECM. mimetics, such PG545, have been developed antitumor agents are designed suppress angiogenesis inhibiting heparanase competing for HS-binding domain factors. However, how PG545 exerts its effect remains incompletely...
Summary Idiopathic multicentric Castleman disease (iMCD) is a rare haematological disorder characterized by generalized lymphadenopathy with atypical histopathological features and systemic inflammation caused cytokine storm involving interleukin‐6 (IL‐6). Three clinical subtypes are recognized: thrombocytopenia, anasarca, fever, renal dysfunction, organomegaly (iMCD‐TAFRO); idiopathic plasmacytic (iMCD‐IPL), thrombocytosis hypergammaglobulinaemia; iMCD‐not otherwise specified (iMCD‐NOS),...
Abstract Idiopathic multicentric Castleman disease (iMCD) is a rare hematologic disorder with an unknown etiology. Clinical presentation heterogeneous, ranging from mild constitutional symptoms lymphadenopathy to life-threatening multiorgan dysfunction. International, consensus treatment guidelines developed in 2018 relied upon limited number of clinical trials and small case series; however, our knowledge, real-world performance these recommendations has not been subsequently studied....
Castleman disease (CD) describes a group of rare lymphoproliferative disorders that exhibit wide range symptomatology and degree lymphadenopathy, particularly across the two forms CD with unknown etiology, unicentric (UCD) HHV-8-negative/idiopathic multicentric (iMCD). Whereas UCD cases typically present localized lymphadenopathy mild symptoms, iMCD involves cytokine-storm driven symptoms three recognized clinical phenotypes. Increasingly, there are anecdotal reports do not fit into this...
A better understanding of the mechanisms regulating CD8+ T cell differentiation is essential to develop new strategies fight infections and cancer. Using genetic mouse models blocking antibodies, we uncovered cellular molecular by which Notch signaling favors efficient generation effector cells. Fibroblastic reticular cells from secondary lymphoid organs, but not dendritic cells, were dominant source signals in via Delta-like1/4 ligands within first 3 days immune responses vaccination or...
Lymph nodes play a key role in maintaining fluid balance homeostatic and inflamed tissues provide fibroblastic niche environments for optimal immune cell positioning interaction. Here, we used single-cell spatial transcriptomic analyses combination with high-resolution imaging to molecularly define functionally characterize niche-forming cells that control inflammation-driven remodeling human lymph nodes. Fibroblastic reticular responded inflammatory perturbation activation expansion of...
7082 Background: Idiopathic multicentric Castleman disease (iMCD) is a hematologic disorder treated by oncologists and characterized diffuse lymphadenopathy systemic inflammation that can cause multi-organ failure. iMCD subtypes include thrombocytopenia, anasarca, fever, renal dysfunction, organomegaly (TAFRO) not otherwise specified. Siltuximab, an interleukin 6 (IL6) antagonist, the only FDA-approved treatment. For patients with severe worsening after siltuximab, consensus guidelines...
NK cells are important for the control of vaccinia virus (VV) in vivo. Recent studies have shown that multiple pathways required effective activation cells. These include both TLR-dependent and -independent pathways, as well NKG2D activating receptor recognizes host stress-induced ligands. However, it remains largely unknown what controls upregulation ligands response to VV infection. In this study using C57BL/6 mice, we first showed IL-18 is critical NK-cell viral clearance. We then...
Nonhematopoietic lymph node stromal cells (LNSCs) regulate lymphocyte trafficking, survival, and function for key roles in host defense, autoimmunity, alloimmunity, lymphoproliferative disorders. However, the study of LNSCs human diseases is complicated by a dependence on viable lymphoid tissues, which are most often excised prior to establishment specific diagnosis. Here, we demonstrate that cryopreservation can be used bank tissue disease. Using tonsils nodes (LN), fragments were...
The coronavirus disease of 2019 (COVID-19) caused by severe acute respiratory syndrome 2 (SARS-CoV-2) infection has resulted in increased morbidity and mortality patients with impaired immunity, hematologic malignancies, immunosuppressive regimens. COVID-19 can cause a cytokine storm some benefiting from blockade the pro-inflammatory cytokine, interleukin 6 (IL6). As Castleman (CD) is an atypical lymphoproliferative disorder that involve often requires therapies, including IL6 inhibition, we...
NK cells are critical for the control of viral infections. Studies have shown that efficient cell activation in response to infection with VV vivo requires multiple pathways, including NKG2D pathway. We recently IL-18 is necessary through upregulation ligand Rae-1 on DCs upon infection. However, how IL-18R signaling accessory contributes up-regulation remains be defined. In this study, we found IL-18-mediated cells, macrophages and DCs, dependent MyD88-PI3K further PI3K led inhibition GSK-3,...
Telomerase extends chromosome ends in somatic and germline stem cells to ensure continued proliferation. Mutations genes critical for telomerase function result telomeropathies such as dyskeratosis congenita, frequently resulting spontaneous bone marrow failure. A congenita mutation TPP1 (K170∆) that specifically compromises recruitment telomeres is a valuable tool evaluate telomerase-dependent telomere length maintenance mice. We used CRISPR-Cas9 generate mouse knocked the equivalent of...
Abstract Lymph nodes (LNs) are secondary lymphoid organs where lymphocytes interact with antigen presenting cells to initiate adaptive immune responses within microenvironments established by resident stromal cells. LNs also the major site of growth follicular lymphoma (FL) and chronic lymphocytic leukemia (CLL), B cell neoplasms that alter architecture in highly stereotypic ways. To characterize FL CLL LN microenvironment, we developed a pipeline for single-cell RNA sequencing all We...