A5073199778- CAR-T cell therapy research
- Immune Cell Function and Interaction
- Viral Infectious Diseases and Gene Expression in Insects
- Ubiquitin and proteasome pathways
- Biosensors and Analytical Detection
- Chronic Lymphocytic Leukemia Research
- Epigenetics and DNA Methylation
- T-cell and B-cell Immunology
- DNA Repair Mechanisms
- Immunotherapy and Immune Responses
- Renal and related cancers
- Advanced Biosensing Techniques and Applications
- Protein Degradation and Inhibitors
- Nanowire Synthesis and Applications
- Acute Myeloid Leukemia Research
- Cancer Immunotherapy and Biomarkers
- Chronic Myeloid Leukemia Treatments
- Bladder and Urothelial Cancer Treatments
- Virus-based gene therapy research
- Insect Resistance and Genetics
- Lymphoma Diagnosis and Treatment
- RNA regulation and disease
- Receptor Mechanisms and Signaling
- Pharmaceutical Economics and Policy
- Biochemical and Molecular Research
Cornell University
2019-2025
Kettering University
2024
Memorial Sloan Kettering Cancer Center
2020-2024
Weill Cornell Medicine
2021
Stony Brook University
2016-2017
Machine learning–enabled perception-based detection of protein biomarkers was achieved in gynecologic cancer patient biofluids.
Abstract Intravesical therapies have been the mainstay of bladder cancer (BC) management; however, their efficacy is limited by toxicities, recurrences, and supply shortages. Consequently, many patients are recommended cystectomy, which fraught with complications. Thus, bladder-sparing treatments present a major, unmet clinical need. Chimeric antigen receptor (CAR) T cell therapy, wherein cells engineered to express an artificial target, immunotherapeutic approach in hematologic...
Maintaining genomic integrity during DNA replication is essential for cellular survival and preventing tumorigenesis. Proliferating cell nuclear antigen (PCNA) functions as a processivity factor replication, posttranslational modification of PCNA plays key role in coordinating repair against replication-blocking lesions by providing platform to recruit factors required cycle control. Here, we identify human SDE2 new genome surveillance regulated interaction. contains an N-terminal...
Abstract While effective in specific settings, adoptive chimeric antigen receptor (CAR) T cell therapy for cancer requires further improvement and optimization. Our previous results show that CD40L-overexpressing CAR cells mobilize endogenous immune effectors, resulting improved antitumor immunity. However, the populations required this protective effect remain to be identified. Here we show, by analyzing Batf3 −/− mice lacking CD103 + conventional dendritic type 1 (cDC1) subpopulation...
CD33 is a tractable target in acute myeloid leukemia (AML) for chimeric antigen receptor (CAR) T cell therapy, but clinical success lacking. We developed 3P14HLh28Z, novel CD33-directed CD28/CD3Z-based CAR derived from high-affinity binder obtained through membrane-proximal fragment immunization humanized mice. found that exclusively with the domain of necessary identification binders Compared clinically validated lintuzumab-based cells targeting distal epitopes, 3P14HLh28Z showed enhanced...
Accumulating evidence indicates that paternal age correlates with disease risk in children. De novo gain-of-function mutations the FGF-RAS-MAPK signaling pathway are known to cause a subset of genetic diseases associated advanced age, such as Apert syndrome, achondroplasia, Noonan and Costello syndrome. It has been hypothesized adult spermatogonial stem cells pathogenic clonally expanded over time propagate offspring. However, no model system exists interrogate mammalian germline cell...
Chimeric antigen receptor (CAR) T-cell therapy has resulted in remarkable clinical success the treatment of B-cell malignancies. However, its efficacy solid tumors is limited, primarily by target heterogeneity. To overcome heterogeneity, we developed CAR T cells that overexpress LIGHT, a ligand both lymphotoxin-β on cancer and herpes virus entry mediator immune cells. LIGHT-expressing displayed antigen-directed cytotoxicity mediated antigen-independent killing through interaction LIGHT with...
<p>(A) ELISA quantification of soluble LIGHT in cell culture media after 24 hours incubation. (B) Supernatant from LIGHT-CAR T cells and second-generation CAR were added to corresponding vitro cytolysis was assessed against AsPC1. Data is representative 2 independent experiments two different donors. (C) MIAPACA2. (D) Cytotoxicity assay with various mesothelin-directed constructs the addition recombinant 3 (E) Mesothelin-directed exhibited similar proliferation a repetitive antigen...
<p>(A) Violin plots showing quality metrics of single cells included in downstream analysis. nCount RNA: number RNA unique molecular identifiers (UMI); nFeature detected genes; nCount_ADT: antibody UMI; nFeature_ADT: antibodies; percent.mt: percentage mitochondrial gene expression; HTO_margin: difference between signals for the hashtag with highest signal and second signal. (B) (C) Weighted-nearest neighbor (WNN) UMAP colored by condition (CAR T cell construct timepoint) (top) CD4+ vs...
<p>(A) Flow cytometric analysis of LTβR expression MIAPACA2 cells after CRISPR knockout (KO). KO were also transduced with non-signaling without intracellular signaling portion (tLTBR). (B) healthy human donor-derived mesothelin-targeted CAR T cocultured tumor expressing GFP and firefly luciferase at different effector to ratios. Bioluminescence was measured 72 hours later plotted as a percentage the signal detected in coculture non-functional Meso-DEL-CAR cells. Plots represent 3...
<p>(A) CAR T cells infiltration and expression of LIGHT at the tumor site was quantified by flow cytometric analysis on day 14 post cell treatment. (B) (C) Quantification per gram AsPC1 mass Plot is representative 4 to 5 mice treatment group. Immunohistochemistry staining mesothelin-negative cancer line, Panc1. Negative control. (D) mesothelin-positive MDA-MB-231. Positive (E) various PDX slides samples validate their mesothelin expression. (F) Flow in PDAC2, one selected for vivo...
<p>(A) Histopathological analysis images of certain organs in the 3 CAR-treated groups following full necropsy on day 30. Representative regions displaying lesion or absence at 20magnification are stained with H&E. Scale bar 100 microns. (B) Histologic examination various and tissues 30 after CAR T cell treatment. (C) Serum chemistry values mice Red represents higher than reference range blue lower range.</p>
<p>(A) Transgene expression of the CAR constructs after retroviral transduction human T cells by flow cytometry. CD19 were used as irrelevant cell control. (B-D) Healthy donor-derived mesothelin-targeted cocultured with tumor expressing GFP and firefly luciferase at different effector to ratios. Bioluminescence was measured 72 hours later plotted a percentage signal detected alone (max bioluminescence signal). Associated mesothelin corresponding mesothelin-positive lines are shown. JMN...
<div>Abstract<p>Chimeric antigen receptor (CAR) T-cell therapy has resulted in remarkable clinical success the treatment of B-cell malignancies. However, its efficacy solid tumors is limited, primarily by target heterogeneity. To overcome heterogeneity, we developed CAR T cells that overexpress LIGHT, a ligand both lymphotoxin-β on cancer and herpes virus entry mediator immune cells. LIGHT-expressing displayed antigen-directed cytotoxicity mediated antigen-independent killing...
Abstract Conventional molecular recognition elements, such as antibodies, present issues for the development of biomolecular assays use in point-of-care devices, implantable/wearables, and under-resourced settings. Additionally, antibody use, especially highly multiplexed applications, can be slow costly. We developed a perception-based platform based on an optical nanosensor array that leverages machine learning algorithms to detect multiple protein biomarkers biofluids. demonstrated this...
<h3>Background</h3> Glioblastoma (GBM) is the most lethal form of primary brain tumor in adults, with a 95% five-year mortality rate. Current therapy consists surgical resection, chemotherapy, and radiotherapy. However, there remains an urgent need for novel therapies as recent trials have failed to improve overall survival.<sup>1</sup> A new approach target GBM administration Chimeric Antigen Receptor (CAR) T cells treat relapsed/refractory disease.<sup>2</sup> To date, multiple clinical...