A5050727908- Lymphoma Diagnosis and Treatment
- CAR-T cell therapy research
- Immune Cell Function and Interaction
- Monoclonal and Polyclonal Antibodies Research
- NF-κB Signaling Pathways
- Alzheimer's disease research and treatments
- Photosynthetic Processes and Mechanisms
- Immune Response and Inflammation
- Cancer Immunotherapy and Biomarkers
- Immunotherapy and Immune Responses
- Hematopoietic Stem Cell Transplantation
- Chronic Lymphocytic Leukemia Research
- Lung Cancer Treatments and Mutations
- Cancer Research and Treatments
- Plant Stress Responses and Tolerance
- Acute Lymphoblastic Leukemia research
- T-cell and B-cell Immunology
- Radiopharmaceutical Chemistry and Applications
- Cancer Genomics and Diagnostics
- RNA and protein synthesis mechanisms
- Aluminum toxicity and tolerance in plants and animals
- Trace Elements in Health
- Single-cell and spatial transcriptomics
- Glycosylation and Glycoproteins Research
- Adenosine and Purinergic Signaling
Cancer Genetics (United States)
2023-2025
Johns Hopkins University
2018-2025
Sidney Kimmel Comprehensive Cancer Center
2019-2025
Sidney Kimmel Cancer Center
2023-2025
Johns Hopkins Medicine
2021-2025
Stockholm University
2021-2025
Howard Hughes Medical Institute
2019-2024
University of Baltimore
2018-2024
Cancer Research Center
2024
Attocube Systems (Germany)
2023
(tumor protein p53) is the most commonly mutated cancer driver gene, but drugs that target mutant tumor suppressor genes, such as
Bispecific T cell–engaging antibodies capable of specifically killing cancer cells expressing mutant RAS neoantigens were generated.
Efficient acclimation to different growth light intensities is essential for plant fitness. So far, most studies on have been conducted with plants grown under constant regimes, but more recent work indicated that fluctuating or field conditions may result in physiological properties of plants. Thale cress (Arabidopsis thaliana) was three (LL: 25 μmol photons m-2 s-1; NL: 100 HL: 500 s-1) and natural (NatL) conditions. We performed a thorough characterization the morphological,...
Significance The lack of viable tumor-specific targets continues to thwart efforts implement selective anticancer drugs in the clinic. Clonal loss heterozygosity (LOH) occurs great majority human tumors and represents an irreversible genetic alteration present cancer cells that unequivocally distinguishes them from normal cells. Here, we report development NASCAR (Neoplasm-targeting Allele-Sensing CAR), a platform comprising pairwise chimeric receptors for detecting targeting LOH events...
Abstract Silk is a unique, remarkably strong biomaterial made of simple protein building blocks. To date, no synthetic method has come close to reproducing the properties natural silk, due complexity and insufficient understanding mechanism silk fiber formation. Here, we use combination bulk analytical techniques nanoscale methods, including nano-infrared spectroscopy coupled with atomic force microscopy, probe structural characteristics directly, transitions, evolution associated mechanical...
Abstract Evergreen conifers in boreal forests can survive extremely cold (freezing) temperatures during long dark winter and fully recover summer. A phenomenon called “sustained quenching” putatively provides photoprotection enables their survival, but its precise molecular physiological mechanisms are not understood. To unveil them, here we have analyzed seasonal adjustment of the photosynthetic machinery Scots pine ( Pinus sylvestris ) trees by monitoring multi-year changes weather,...
Immunotherapies such as chimeric antigen receptor (CAR) T cells and bispecific antibodies redirect healthy to kill cancer expressing the target antigen. The pan-B cell antigen-targeting immunotherapies have been remarkably successful in treating B malignancies. Such therapies also result near-complete loss of cells, but this depletion is well tolerated by patients. Although analogous targeting pan-T markers could, theory, help control cancers, concomitant would severe unacceptable...
Abstract TCR-mediated activation of the transcription factor NF-κB is required for T cell proliferation, survival, and effector differentiation. Although this pathway subject intense study, it not known whether TCR signaling to digital (switch-like) or analog in nature. Through analysis phosphorylation degradation IκBα nuclear translocation subunit RelA, we show that TCR-directed digital. Furthermore, digitization occurs well upstream IκB kinase complex, as protein C θ immunologic synapse...
Targeted therapies and checkpoint blockade therapy (CBT) have shown efficacy for patients with Hodgkin lymphoma (HL) in the relapsed refractory (R/R) setting, but once discontinued owing to progression or side effects, it is unclear how successful further will be. Moreover, there are no data on optimal sequencing of these treatments standard other novel agents. In a multicenter, retrospective analysis, we investigated whether exposure CBT could sensitize HL subsequent therapy.Seventeen...
Assembly of a multiprotein complex containing the adaptor protein p62 promotes NF-κB activation in T cells.
Abstract Chimeric antigen receptor (CAR) T cells have emerged as a promising class of therapeutic agents, generating remarkable responses in the clinic for subset human cancers. One major challenge precluding wider implementation CAR therapy is paucity tumor-specific antigens. Here, we describe development targeting isocitrate dehydrogenase 2 (IDH2) with R140Q mutation presented on cell surface complex common leukocyte allele, HLA-B*07:02. Engineering hinge domain CAR, well crystal...
Abstract Specificity remains a major challenge to current therapeutic strategies for cancer. Mutation associated neoantigens (MANAs) are products of genetic alterations, making them highly specific targets. MANAs HLA-presented (pHLA) peptides derived from intracellular mutant proteins that otherwise inaccessible antibody-based therapeutics. Here, we describe the cryo-EM structure an antibody-MANA pHLA complex. Specifically, determine TCR mimic (TCRm) antibody bound its MANA target, KRAS G12V...
Abstract Alzheimer’s disease (AD) is the most common cause of dementia worldwide. AD brains display deposits insoluble amyloid plaques consisting mainly aggregated amyloid-β (Aβ) peptides, and Aβ oligomers are likely a toxic species in pathology. patients altered metal homeostasis, show elevated concentrations metals such as Cu, Fe, Zn. Yet, chemistry pathology remains unclear. Ni(II) ions known to interact with but nature effects interactions unknown. Here, we use numerous biophysical...
Two types of engineered T cells have been successfully used to treat patients with cancer, one an antigen recognition domain derived from antibodies [chimeric receptors (CARs)] and the other cell (TCRs). CARs use high-affinity antigen-binding domains costimulatory induce activation but can only react against target relatively high amounts antigen. TCRs a much lower affinity for their antigens displaying few molecules. Here, we describe new type receptor, called Co-STAR (for synthetic TCR...
Despite exciting developments in cancer immunotherapy, its broad application is limited by the paucity of targetable antigens on tumor cell surface. As an intrinsic cellular pathway, nonsense-mediated decay (NMD) conceals neoantigens through destruction RNA products from genes harboring truncating mutations. We developed and conducted a high-throughput screen, based ratiometric analysis transcripts, to identify critical mediators NMD human cells. This screen implicated disruption kinase...
Patients with myeloid neoplasms loss-of-function TP53 mutations and erythroid differentiation have poor outcomes, a better understanding of disease biology is required. Upregulation interferon-γ (IFN-γ) signaling has been associated acute leukemia (AML) progression chemotherapy resistance, but its drivers remain unclear. In this study, we found that the surface receptor C-C motif chemokine receptor-like 2 (CCRL2) overexpressed in AML compared to other subtypes healthy hematopoietic cells....
Immune checkpoint inhibitors (ICIs) are approved in relapsed classic Hodgkin lymphoma (cHL). The safety and effectiveness of allogeneic blood or marrow transplantation (alloBMT) ICI-pretreated patients with cHL remain unclear. aim this study is to assess outcomes receiving ICIs before alloBMT using post-transplantation cyclophosphamide (PTCy) graft-versus-host-disease (GVHD) prophylaxis. We performed a retrospective relapsed/refractory undergoing PTCy at Johns Hopkins between November 2004...