A5038122768- Immunotherapy and Immune Responses
- Cancer Immunotherapy and Biomarkers
- CAR-T cell therapy research
- T-cell and B-cell Immunology
- Immune Cell Function and Interaction
- Monoclonal and Polyclonal Antibodies Research
- Melanoma and MAPK Pathways
- vaccines and immunoinformatics approaches
- SARS-CoV-2 and COVID-19 Research
- Cutaneous Melanoma Detection and Management
- Multiple Sclerosis Research Studies
- Cancer Genomics and Diagnostics
- Peptidase Inhibition and Analysis
- Peripheral Neuropathies and Disorders
- Signaling Pathways in Disease
- Cell Adhesion Molecules Research
- Immunodeficiency and Autoimmune Disorders
- Atherosclerosis and Cardiovascular Diseases
- Cellular Mechanics and Interactions
- melanin and skin pigmentation
- Receptor Mechanisms and Signaling
- Nanoplatforms for cancer theranostics
- Protease and Inhibitor Mechanisms
- Multiple Myeloma Research and Treatments
- Immune cells in cancer
New York University
2016-2025
NYU Langone Health
2014-2025
NYU Langone’s Laura and Isaac Perlmutter Cancer Center
2022-2024
Eastern Cooperative Oncology Group
2013-2023
York University
2013-2021
Hinge Health
2020
Georgia Institute of Technology
2019
Columbia University Irving Medical Center
2018
Indiana University School of Medicine
2016
Sabin Vaccine Institute
2013
High surface expression of programmed death 1 (PD-1) is associated with T-cell exhaustion; however, the relationship between PD-1 and dysfunction has not been delineated. We developed a model to study signaling in primary human T cells how affected function. By determining number receptor/peptide-MHC complexes needed initiate Ca(2+) flux, we found that ligation dramatically shifts dose-response curve, making much less sensitive receptor-generated signals. Importantly, other functions were...
T cells expressing antigen-specific T-cell receptors (TCRs) can mediate effective tumor regression, but they often also are accompanied by autoimmune responses. To determine the TCR affinity threshold defining optimal balance between antitumor activity and autoimmunity in vivo , we used a unique self-antigen system comprising seven human melanoma gp100(209–217)-specific TCRs spanning physiological affinities (1–100 μM). We found that vitro responses determined affinity, except one case was...
Immune checkpoint inhibitors (anti-CTLA-4, anti-PD-1, or the combination) enhance anti-tumor immune responses, yielding durable clinical benefit in several cancer types, including melanoma. However, a subset of patients experience immune-related adverse events (irAEs), which can be severe and result treatment termination. To date, no biomarker exists that predict development irAEs. We hypothesized pre-treatment antibody profiles identify who possess sub-clinical autoimmune phenotype...
High C reactive protein (CRP) levels have been reported to be associated with a poor clinical outcome in number of malignancies and programmed cell death 1 immune checkpoint blockade patients advanced cancer. Little is known about the direct effects CRP on adaptive immunity Therefore, we investigated how impacted function T cells dendritic (DCs) from melanoma.
The TCR integrates forces in its triggering process upon interaction with pMHC. Force elicits catch-slip bonds strong pMHCs but slip-only weak pMHCs. We develop two models and apply them to analyze 55 datasets, demonstrating the models' ability quantitatively integrate classify a broad range of bond behaviors biological activities. Comparing generic two-state model, our can distinguish class I from II MHCs correlate their structural parameters TCR/pMHC's potency trigger T cell activation....
Susceptibility to multiple sclerosis (MS) is associated with the human histocompatibility leukocyte antigen (HLA)-DR2 haplotype, suggesting that major complex class II–restricted presentation of central nervous system–derived antigens important in disease process. Antibodies specific for defined HLA-DR2–peptide complexes may therefore be valuable tools studying MS. We have used phage display technology select HLA-DR2–peptide-specific antibodies from HLA-DR2–transgenic mice immunized HLA-DR2...
According to this study, the strongest T cell receptor ligands in vitro do not necessarily induce responses vivo, suggesting that vaccine designers may need reconsider their strategies.
Abstract Purpose: Adjuvant immunotherapy produces durable benefit for patients with resected melanoma, but many develop recurrence and/or immune-related adverse events (irAE). We investigated whether baseline serum autoantibody (autoAb) signatures predicted and severe toxicity in treated adjuvant nivolumab, ipilimumab, or ipilimumab plus nivolumab. Experimental Design: This study included 950 patients: 565 from CheckMate 238 (408 versus 157 nivolumab) 385 915 (190 nivolumab 195 nivolumab)....
Two-dimensional (2D) kinetic analysis directly measures molecular interactions at cell-cell junctions, thereby incorporating inherent cellular effects. By comparison, three-dimensional (3D) probes the intrinsic physical chemistry of interacting molecules isolated from cell. To understand how T-cell tumor reactivity relates to 2D and 3D binding parameters compare them, we performed analyses a panel human receptors (TCRs) with melanoma self-antigen peptide (gp100209 -217 ) bound peptide-major...
Highlights•CD3γε and CD3δε can individually bind to the TCR yield a two-sided binding model•CD3γε binds β subunit α subunit•The molecular basis of TCR-CD3 interactions is examined through NMR spectroscopy•The extracellular structure revealed using computational dockingSummaryAntigen recognition peptide-major histocompatibility complexes (pMHCs) by T cells, key step in initiating adaptive immune responses, performed cell receptor (TCR) bound CD3 heterodimers. However, biophysical transmission...
The objective of this study was to determine the impact multiple sclerosis (MS) disease-modifying therapies (DMTs) on development cellular and humoral immunity severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) infection.Patients with MS aged 18 60 years were evaluated for anti-nucleocapsid anti-Spike receptor-binding domain (RBD) antibody electro-chemiluminescence immunoassay; responses Spike protein, RBD, N-terminal multiepitope bead-based immunoassays (MBI); live virus...
Abstract T cell receptors (TCR) are pivotal in mediating tumour cytolysis via recognition of mutation-derived neoantigens (neoAgs) presented by major histocompatibility class-I (MHC-I). Understanding the factors governing emergence neoAg from somatic mutations is a focus current research. However, structural and cellular determinants controlling TCR neoAgs remain poorly understood. This study describes multi-level analysis model B16F10 murine melanoma, H2-D b /Hsf2 p.K72N 68-76 , as well its...
T-cell-based immunotherapies have revolutionized cancer treatment, yet only a minority of patients respond to these approaches, significantly constrained by the limited knowledge tumor-specific antigens. Here we present comprehensive map T cell targets across 21 types, revealing actionable in 86% tumors. To define repertoire targets, conducted pan-cancer analysis integrating data from 7,473 RNA-Seq datasets, 1,564 immunopeptidomes and 208 single-cell comparing against 17,384 normal samples...
ABSTRACT The pancreas tumor microbiota may influence microenvironment and survival in early-stage pancreatic ductal adenocarcinoma (PDAC); however, current studies are limited small. We investigated the relationship of to 201 surgically resected patients with localized PDAC (Stages I–II), from Cancer Genome Atlas (TCGA) International Consortium (ICGC) cohorts. characterized microbiome using RNA-sequencing data. examined association overall (OS), via meta-analysis Cox PH model. A microbial...
T cell selection and maturation in the thymus depends on interactions between receptors (TCRs) different self-peptide-major histocompatibility complex (pMHC) molecules. We show that affinity of OT-I TCR for its endogenous positively selecting ligands, Catnb-H-2Kb Cappa1-H-2Kb, is significantly lower than previously reported altered peptide ligands. To understand how these extremely weak ligands produce signals maturing thymocytes, we generated soluble monomeric dimeric peptide-H-2Kb Soluble...