A5083361833- Bladder and Urothelial Cancer Treatments
- Cancer Immunotherapy and Biomarkers
- Immune Cell Function and Interaction
- Immune cells in cancer
- T-cell and B-cell Immunology
- Immunotherapy and Immune Responses
- Epigenetics and DNA Methylation
- IL-33, ST2, and ILC Pathways
- Reproductive System and Pregnancy
- Renal cell carcinoma treatment
- HIV Research and Treatment
- Urinary and Genital Oncology Studies
- Cytomegalovirus and herpesvirus research
- CAR-T cell therapy research
- Ferroptosis and cancer prognosis
- Single-cell and spatial transcriptomics
- MRI in cancer diagnosis
- Immune responses and vaccinations
- HIV/AIDS Research and Interventions
- Acute Myeloid Leukemia Research
- Immune Response and Inflammation
- Invertebrate Immune Response Mechanisms
- Renal and related cancers
- SARS-CoV-2 and COVID-19 Research
- Radiomics and Machine Learning in Medical Imaging
Tisch Hospital
2019-2024
Icahn School of Medicine at Mount Sinai
2018-2024
Open University of Israel
2022-2024
Mount Sinai Hospital
2019-2023
New York Proton Center
2022
Mount Sinai Health System
2019
Tisch Cancer Institute
2019
Aaron Diamond AIDS Research Center
2004-2019
Rockefeller University
2004-2019
Cancer Institute (WIA)
2019
Given its population of CCR5-expressing, immunologically activated CD4+ T cells, the gastrointestinal (GI) mucosa is uniquely susceptible to human immunodeficiency virus (HIV)-1 infection. We undertook this study assess whether a preferential depletion mucosal cells would be observed in HIV-1–infected subjects during primary infection period, examine anatomic subcompartment from which these are depleted, and suppressive highly active antiretroviral therapy could result complete immune...
Both genetics and environment contribute to human NK cell diversity.
Individuals heterozygous for HLA haplotypes have increased NK cell diversity because of distinct education pathways.
Abstract Human natural killer (NK) cells in peripheral blood perform many functions, and classification of specific subsets has been a longstanding goal. We report single-cell RNA sequencing NK cells, comparing gene expression unstimulated interleukin (IL)-2–activated from healthy cytomegalovirus (CMV)-negative donors. Three cell resembled well-described populations; CD56brightCD16−, CD56dimCD16+CD57−, CD56dimCD16+CD57+. CD56dimCD16+CD57− subdivided to include population with higher...
Abstract Cystectomy is a standard treatment for muscle-invasive bladder cancer (MIBC), but it life-altering. We initiated phase 2 study in which patients with MIBC received four cycles of gemcitabine, cisplatin, plus nivolumab followed by clinical restaging. Patients achieving complete response (cCR) could proceed without cystectomy. The co-primary objectives were to assess the cCR rate and positive predictive value composite outcome: 2-year metastasis-free survival forgoing immediate...
Abstract Natural killer (NK) cells are innate lymphoid (ILCs) contributing to immune responses microbes and tumors. Historically, their classification hinged on a limited array of surface protein markers. Here, we used single-cell RNA sequencing (scRNA-seq) cellular indexing transcriptomes epitopes by (CITE-seq) dissect the heterogeneity NK cells. We identified three prominent cell subsets in healthy human blood: NK1, NK2 NK3, further differentiated into six distinct subgroups. Our findings...
The functional diversity of natural killer (NK) cell repertoires stems from differentiation, homeostatic, receptor-ligand interactions and adaptive-like responses to viral infections. In the present study, we generated a single-cell transcriptional reference map healthy human blood- tissue-derived NK cells, with temporal resolution fate-specific expression gene-regulatory networks defining differentiation. Transfer learning facilitated incorporation tumor-infiltrating transcriptomes (39...
The CD1 family of proteins binds self and foreign glycolipids for presentation to CD1-restricted T cells. To identify previously uncharacterized active ligands, especially those microbial origin, numerous were synthesized tested their ability stimulate mouse human natural killer (NKT) They included analogs the well known NKT cell agonist α-galactosyl ceramide (α-GalCer), bacterial glycolipids, variations self-glycolipid, sulfatide. Bacterial α-galacturonosyl-ceramides from Sphingomonas...
We characterized vaccine-induced cellular responses to rabies virus in naive adult volunteers. Contrary current paradigms, we observed potent and prolonged vitro NK cell cytokine production degranulation after restimulation of PBMCs with inactivated vaccinated, but not unvaccinated, individuals. This "recall" response was absolutely dependent on Ag-specific IL-2 from CD45RO(+) CD4(+) T cells as well IL-12 IL-18 accessory cells. Importantly, represented over 70% all IFN-gamma-secreting...
Inhibiting natural killer cells in AIDS The human leukocyte antigen (HLA) gene complex varies enormously among individuals and helps explain individual variation immunity to infectious diseases. Ramsuran et al. examined data from almost 10,000 HIV infections. Expression of the HLA-A - B alleles was associated with higher viral load, reduced CD4 + T cell counts, accelerated progression AIDS. Higher levels expression increased HLA-E , which blocks a specific receptor (NKG2A) on immune that...
Abstract During early pregnancy, decidual innate lymphoid cells (dILCs) interact with surrounding maternal and invading fetal extravillous trophoblasts (EVT). Here, using mass cytometry, we characterise five main dILC subsets: NK (dNK)1–3, ILC3s proliferating cells. Following stimulation, dNK2 dNK3 produce more chemokines than dNK1 including XCL1 which can act on both dendritic EVT. In contrast, express receptors Killer-cell Immunoglobulin-like Receptors (KIR), indicating they respond to HLA...
Natural killer (NK) cells are large granular lymphocytes that express a diverse array of germline encoded inhibitory and activating receptors for MHC Class I I-like molecules, classical co-stimulatory ligands, cytokines. The ability NK to be very rapidly activated by inflammatory cytokines, secrete effector kill infected or stressed host cells, suggests they may among the early responders during infection. Recent studies have also identified small number pathogen-derived ligands can bind...
Abstract Purpose: To define dominant molecular and cellular features associated with PD-1/PD-L1 blockade resistance in metastatic urothelial cancer. Experimental Design: We pursued an unbiased approach using bulk RNA sequencing data from two clinical trials to discover (IMvigor 210) validate (CheckMate 275) pretreatment then generated single-cell (scRNA-seq) muscle-invasive bladder cancer specimens dissect the composition underlying identified gene signatures. Results: adaptive immune...
Natural killer (NK) cells are innate immune that contribute to host defense against virus infections. NK respond severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in vitro and activated patients with disease 2019 (COVID-19). However, by which mechanisms detect SARS-CoV-2-infected remains largely unknown. Here, we show the Non-structural protein 13 of SARS-CoV-2 encodes for a peptide is presented human leukocyte antigen E (HLA-E). In contrast self-peptides, viral prevents binding...
The functional status of immune cells in the tumor microenvironment and characteristics may explain bacillus Calmette-Guérin (BCG) failure high-risk non-muscle-invasive bladder cancer (NMIBC).To characterize molecular correlates post-BCG high-grade (HG) recurrence using multiomics analysis.Patients with BCG-treated NMIBC (n = 156) were included study. Metachronous tumors analyzed RNA sequencing 170) whole-exome 195). Urine samples for immuno-oncology-related proteins 190) tumor-derived DNA...
Rapid cell-mediated immune responses, characterized by production of proinflammatory cytokines, such as IFN-gamma, can inhibit intraerythrocytic replication malaria parasites and thereby prevent onset clinical malaria. In this study, we have the kinetics cellular sources very early IFN-gamma response to Plasmodium falciparum-infected RBCs among human PBMCs. We find that NK cells dominate (12-18 h) response, T contribute equally at 24 h, increasingly from 48 h onward. also although gammadelta...
Subsets of NK cells can have distinct functions. Here, we report that >25% human peripheral blood express HLA-DR after culture with IL-2. This be driven by an expansion a small subset expressing HLA-DR, in contrast to previous assumptions is upregulated on previously negative cells. HLA-DR-expressing showed enhanced degranulation susceptible target and expressed chemokine receptor CXCR3, which facilitated their enrichment following exposure CXCL11/I-TAC. Suggesting important role immune...