A5067684160- HIV Research and Treatment
- Single-cell and spatial transcriptomics
- Immune Cell Function and Interaction
- Immunotherapy and Immune Responses
- Monoclonal and Polyclonal Antibodies Research
- T-cell and B-cell Immunology
- Cancer Cells and Metastasis
- Glioma Diagnosis and Treatment
- Cancer Genomics and Diagnostics
- Hepatitis C virus research
- HIV/AIDS drug development and treatment
- CAR-T cell therapy research
- Mosquito-borne diseases and control
- Cancer-related molecular mechanisms research
- Sarcoma Diagnosis and Treatment
- Zebrafish Biomedical Research Applications
- Lymphoma Diagnosis and Treatment
- Protein Structure and Dynamics
- Herpesvirus Infections and Treatments
- Extracellular vesicles in disease
- Cancer Immunotherapy and Biomarkers
- Immune responses and vaccinations
- Cancer-related gene regulation
- Epigenetics and DNA Methylation
- HIV, Drug Use, Sexual Risk
New York University
2018-2024
NYU Langone Health
2021-2024
Indiana University School of Medicine
2022-2023
Massachusetts General Hospital
2016-2021
Center for Cancer Research
2016-2021
Harvard University
2016-2021
Icahn School of Medicine at Mount Sinai
2021
University School
2021
National Center for Communicable Diseases
2021
National Institute for Communicable Diseases
2021
Tumor subclasses differ according to the genotypes and phenotypes of malignant cells as well composition tumor microenvironment (TME). We dissected these influences in isocitrate dehydrogenase (IDH)-mutant gliomas by combining 14,226 single-cell RNA sequencing (RNA-seq) profiles from 16 patient samples with bulk RNA-seq 165 samples. Differences between IDH-mutant astrocytoma oligodendroglioma can be primarily explained distinct TME signature genetic events, whereas both types share similar...
Gliomas with histone H3 lysine27-to-methionine mutations (H3K27M-glioma) arise primarily in the midline of central nervous system young children, suggesting a cooperation between genetics and cellular context tumorigenesis. Although H3K27M-glioma are well characterized, their architecture remains uncharted. We performed single-cell RNA sequencing 3321 cells from six primary matched models. found that contain resemble oligodendrocyte precursor (OPC-like), whereas more differentiated malignant...
Triple-negative breast cancer (TNBC) is an aggressive subtype characterized by extensive intratumoral heterogeneity. To investigate the underlying biology, we conducted single-cell RNA-sequencing (scRNA-seq) of >1500 cells from six primary TNBC. Here, show that intercellular heterogeneity gene expression programs within each tumor variable and largely correlates with clonality inferred genomic copy number changes, suggesting genotype drives phenotype individual subpopulations. Clustering...
Programmed cell death-1 (PD-1) is a potent immune checkpoint receptor on T lymphocytes. Upon engagement by its ligands, PD-L1 or PD-L2, PD-1 inhibits activation and can promote tolerance. Antagonism of signaling has proven effective in cancer immunotherapy, conversely, agonists the may have role treating autoimmune disease. Some receptors function as dimers, but been considered monomeric. Here, we show that ligands form dimers consequence transmembrane domain interactions propensity for...
Hematopoiesis culminates in the production of functionally heterogeneous blood cell types. In zebrafish, lack surface antibodies has compelled researchers to use fluorescent transgenic reporter lines label specific fractions. However, these approaches are limited by availability and protein combinations that can be distinguished. Here, we have transcriptionally profiled single hematopoietic cells from zebrafish define erythroid, myeloid, B, T lineages. We also used our approach identify stem...
TAR DNA-binding protein 43 (TDP-43) is genetically and functionally linked to amyotrophic lateral sclerosis (ALS) regulates transcription, splicing, transport of thousands RNA targets that function in diverse cellular pathways. In ALS, pathologically altered TDP-43 believed lead disease by toxic gain-of-function effects on metabolism, as well sequestering endogenous causing its loss function. However, it unclear which the numerous processes disrupted downstream dysfunction neurodegeneration....
The V1V2 region of the HIV-1 envelope is target several broadly neutralizing antibodies (bNAbs). Antibodies to elicited in RV144 clinical trial correlated with a reduced risk HIV infection, but these were without broad activity. targeting also viral load immunized macaques challenged simian immunodeficiency virus (SIV) or simian/human (SHIV). To focus immune responses on V1V2, we engrafted native, glycosylated domain onto five different multimeric scaffold proteins and conducted comparative...
Developing a safe and effective malaria vaccine is critical to reducing the spread resurgence of this deadly disease, especially in children. In recent years, technology has seen expanded development subunit protein, peptide, nucleic acid vaccines. This due their inherent safety, ability tailor immune response, simple storage requirements, easier production, lower expense compared using attenuated inactivated organism-based approaches. However, these new technologies generally have low...
Abstract V2p and V2i antibodies (Abs) that are specific for epitopes in the V1V2 region of HIV gp120 envelope (Env) do not effectively neutralize but mediate Fc-dependent anti-viral activities have been correlated with protection from, or control HIV, SIV SHIV infections. Here, we describe a novel molecular toolbox allows discrimination antigenically functionally distinct polyclonal V2 Ab responses. We identify different patterns induction by infection three separate vaccine regimens aid...
Introduction HIV-1 envelope (Env) is the key target for antibodies (Abs) against virus and thus an important vaccine component. Env synthesized from a gp160 precursor with signal peptide (SP) at its N-terminus. This study investigated influence of SP on antigenicity immunogenicity. Methods proteins two isolates, AA05 AC02, were analyzed as gp120 in their native wild-type (WT) forms chimeras swapped SPs (AA05-02 AC02-05). The WT chimeric assessed glycosylation using monoclonal (mAbs) glycan...
The only HIV vaccine trial for which protective efficacy was detected correlated this with V2-specific Abs that were effectively nonneutralizing. This result has fueled a decade of research focused on designing an capable eliciting V2-focused, polyfunctional bind and trigger various leukocytes to kill the virus restrict viral spread. From numerous candidates designed tested as part our V2-focused preclinical program, we have identified immunogens regimen induces highly durable Ab response in...
The role of vaccine-induced anti-V2 Abs was tested in three protection experiments rhesus macaques. In an experiment using immunogens similar to those the RV144 vaccine trial (Anti-envelope [Env]), nine macaques were coimmunized with gp160
Abstract The human immunodeficiency virus (HIV‐1) envelope glycoprotein spike is targeted by antibodies and therefore represents the main viral antigen for antibody‐based vaccine design. One of challenges in HIV‐1 development inducing efficient immune system recognition response to without establishing an infection. Since enters body at mucosal surfaces, induction these sites a preferred preventive approach. Nasal administration effective route immunization since it can stimulate responses...
Abstract Systemic vaccination of macaques with V1-deleted (ΔV1) envelope immunogens reduce the risk SIV mac251 acquisition by approximately 60%, protective roles played V2-specific ADCC and envelope-specific mucosal IL-17 + NKp44 innate lymphoid cells (ILCs). We investigated whether increased responses to V2 benefit vaccine efficacy delivering oral nanoparticles (NPs) that release V2-scaffolded on Typhoid Toxin B (TTB) large intestine. Strikingly, immunization male abrogated control TTB or...
Abstract Conventional antibodies are composed of two identical sets heavy and light chains, forming a dimer. The CH1 domain the antibody chain is essential for pairing chains. However, certain animals, such as camels sharks, evolved to produce heavy-chain-only (HCAbs) by losing this crucial in some their constant regions. These HCAbs boast unique physicochemical properties that confer significant advantages: smaller size allows improved access target antigens, increased hydrophilicity,...
Introduction Neutralizing antibodies (Abs) are one of the immune components required to protect against viral infections. However, developing vaccines capable eliciting neutralizing Abs effective a broad array HIV-1 isolates has been an arduous challenge. Objective This study sought test aimed induce epitopes at V1V2 apex envelope (Env). Methods Four groups rabbits received DNA vaccine expressing domain CRF01_AE A244 strain on trimeric 2J9C scaffold (V1V2-2J9C) along with protein consisting...
ABSTRACT Synovial sarcoma is an aggressive mesenchymal neoplasm, driven by the SS18-SSX fusion, and characterized immunogenic antigens expression exceptionally low T cell infiltration levels. To study cancer-immune interplay in this disease, we profiled 16,872 cells from 12 human synovial tumors using single-cell RNA-sequencing (scRNA-Seq). manifests antitumor immunity, high cellular plasticity a core oncogenic program, which predictive of immune levels poor clinical outcomes. Using genetic...
The V1V2 region of the HIV-1 Envelope is target several broadly neutralizing antibodies (bNAbs). RV144 vaccinees elicited binding to V1V2, which correlated with a reduced risk HIV infection, yet these were without broad activity. Antibodies targeting V2 also delayed infection and viral load in immunized macaques challenged SIV or SHIV. To focus immune responses on we designed panel immunogens by engrafting native, glycosylated domain onto multimeric scaffold proteins conducted comparative...
Abstract Identification of vulnerable sites defined by broadly neutralizing antibodies (bNAbs) on HIV-1 envelope (Env) is crucial for vaccine design, and we present here a site bNAb M4008_N1, which neutralizes about 40% tier-2 virus panel. A 3.2 Å resolution cryo-EM structure M4008_N1 in complex with BG505 DS-SOSIP reveals large, shallow protein epitope surface centered at the V3 crown gp120 surrounded key glycans. interacts primarily through its hammerhead CDR H3 to form β-sheet interaction...