A5083237199- Immune cells in cancer
- Phagocytosis and Immune Regulation
- Radiomics and Machine Learning in Medical Imaging
- Cancer Immunotherapy and Biomarkers
- Single-cell and spatial transcriptomics
- Pancreatic and Hepatic Oncology Research
- Cancer Genomics and Diagnostics
- Advanced Biosensing Techniques and Applications
- Histone Deacetylase Inhibitors Research
- Immunotherapy and Immune Responses
- TGF-β signaling in diseases
- Epigenetics and DNA Methylation
- RNA modifications and cancer
- Biosimilars and Bioanalytical Methods
- Lung Cancer Treatments and Mutations
- Ferroptosis and cancer prognosis
- Cell Image Analysis Techniques
- Click Chemistry and Applications
- Gastric Cancer Management and Outcomes
- Bioinformatics and Genomic Networks
- Cancer Research and Treatments
- CAR-T cell therapy research
- HER2/EGFR in Cancer Research
- Cancer Cells and Metastasis
- Caveolin-1 and cellular processes
Bloomberg (United States)
2021-2025
Johns Hopkins University
2016-2025
University of Baltimore
2015-2025
Johns Hopkins Medicine
2014-2025
Sidney Kimmel Comprehensive Cancer Center
2016-2025
Convergence
2021-2025
Johns Hopkins Hospital
2025
Sidney Kimmel Cancer Center
2021-2024
Maine Farmland Trust
2019
AC Camargo Hospital
2011-2017
Merkel cell carcinoma (MCC) is a lethal, virus-associated cancer that lacks effective therapies for advanced disease. Agents blocking the PD-1/PD-L1 pathway have demonstrated objective, durable tumor regressions in patients with solid malignancies and efficacy has been linked to PD-L1 expression microenvironment. To investigate whether MCC might be target blockade, we examined expression, its association tumor-infiltrating lymphocytes (TILs), polyomavirus (MCPyV), overall survival....
Abstract Programmed cell death protein 1 (PD-1) inhibitors have modest efficacy as a monotherapy in hepatocellular carcinoma (HCC). A personalized therapeutic cancer vaccine (PTCV) may enhance responses to PD-1 through the induction of tumor-specific immunity. We present results from single-arm, open-label, phase 1/2 study DNA plasmid PTCV (GNOS-PV02) encoding up 40 neoantigens coadministered with plasmid-encoded interleukin-12 plus pembrolizumab patients advanced HCC previously treated...
Abstract Background Novel immunotherapy combination therapies have improved outcomes for patients with hepatocellular carcinoma (HCC), but responses are limited to a subset of patients. Little is known about the inter- and intra-tumor heterogeneity in cellular signaling networks within HCC tumor microenvironment (TME) that underlie modern systemic therapy. Methods We applied spatial transcriptomics (ST) profiling characterize resection specimens from prospective clinical trial neoadjuvant...
Abstract Lungs resected for adenocarcinomas often harbour minute discrete foci of cytologically atypical pneumocyte proliferations designated as adenomatous hyperplasia (AAH). Evidence suggests that AAH represents an initial step in the progression to adenocarcinoma situ (AIS), minimally invasive (MIA) and fully adenocarcinoma. Despite efforts identify predictive markers malignant transformation, alterations driving this are poorly understood. Here we perform targeted next-generation...
Abstract Although specific mutations in the tyrosine kinase domain of epidermal growth factor receptor (EGFR) identify tumors that are responsive to EGFR inhibitors (TKI), these genetic alterations present only a minority patients. Patients with expressing wild-type lack reliable predictive markers their clinical response TKIs. epithelial–mesenchymal transition (EMT) has been inversely correlated cancers EGFR-targeted therapy, precise molecular mechanisms underlying this association have not...
Cancer is a complex disease, driven by aberrant activity in numerous signaling pathways even individual malignant cells. Epigenetic changes are critical mediators of these functional that drive and maintain the phenotype. Changes DNA methylation, histone acetylation noncoding RNAs, posttranslational modifications all epigenetic drivers cancer, independent sequence. These alterations were once thought to be crucial only for phenotype maintenance. Now, also recognized as disrupting essential...
Therapeutic combinations to alter immunosuppressive, solid tumor microenvironments (TME), such as in breast cancer, are essential improve responses immune checkpoint inhibitors (ICI). Entinostat, an oral histone deacetylase inhibitor, has been shown ICIs various models with immunosuppressive TMEs. The precise and comprehensive alterations the TME induced by entinostat remain unknown. Here, we employed single-cell RNA sequencing on HER2-overexpressing tumors from mice treated fully...
Significance The onset of androgen resistance is a major impediment in treating prostate cancer (PCa). However, the underlying molecular mechanisms are not fully understood. Here, we integrate multiple biophysical approaches that report conformational preferences intrinsically disordered protein (IDP) Prostate-Associated Gene 4 (PAGE4) with human biology and nonlinear dynamics. Based on our biophysical, biochemical, cellular data, mathematical model presented suggests mechanism by which...
The treatment of hepatocellular carcinoma (HCC) has been transformed by the use immune checkpoint inhibitors. However, most patients with HCC do not benefit from immunotherapy. There is an urgent need to understand mechanisms that underlie response or resistance immunotherapy for HCC. syngeneic mouse models closely recapitulate heterogeneity human will provide opportunities examine complex interactions between cancer cells and nonmalignant in tumor microenvironment.
Abstract Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy characterized by immunosuppressive tumor microenvironment enriched with cancer-associated fibroblasts (CAF). This study used a convergence approach to identify cell and CAF interactions through the integration of single-cell data from human tumors organoid coculture experiments. Analysis comprehensive atlas PDAC RNA sequencing indicated that density associated increased inflammation epithelial–mesenchymal transition...
Due to the lack of treatment options, there remains a need advance new therapeutics in hepatocellular carcinoma (HCC). The traditional approach moves from initial molecular discovery through animal models human trials novel systemic therapies that improve outcomes for patients with cancer. Computational methods simulate tumors mathematically describe cellular and interactions are emerging as promising tools impact therapy entirely silico, potentially greatly accelerating delivery patients....
Identifying potential resistance mechanisms while tumour cells still respond to therapy is critical delay acquired resistance.
Genomic and transcriptomic analysis has furthered our understanding of many tumors. Yet, thyroid cancer management is largely guided by staging histology, with few molecular prognostic treatment biomarkers. Here, we utilize a large cohort 251 patients 312 samples from two tertiary medical centers perform DNA/RNA sequencing, spatial transcriptomics, multiplex immunofluorescence to identify biomarkers aggressive malignancy. We high-risk mutations discover unique signature disease, the...
Personalized cancer vaccines aim to activate and expand cytotoxic antitumor CD8+ T cells recognize kill tumor cells. However, the role of CD4+ cell activation in clinical benefit these is not well defined. We previously established a personalized neoantigen vaccine (PancVAX) for pancreatic line Panc02, which activates tumor-specific but required combinatorial checkpoint modulators achieve therapeutic efficacy. To determine effects neoantigen-specific activation, we generated (PancVAX2)...
Abstract Purpose: Pancreatic ductal adenocarcinoma (PDAC) patients with tumors enriched for the basal-like molecular subtype exhibit enhanced resistance to standard-of-care treatments and have significantly worse overall survival compared classic subtype–enriched tumors. It is important develop genomic resources, enabling identification of novel putative targets in a statistically rigorous manner. Experimental Design: We compiled single-cell RNA sequencing (scRNA-seq) atlas human pancreas...
Abstract Pancreatic ductal adenocarcinoma (PDAC) carries an extremely poor prognosis, in part resulting from cellular heterogeneity that supports overall tumorigenicity. Cancer associated fibroblasts (CAF) are key determinants of PDAC biology and response to systemic therapy. While CAF subtypes have been defined, the effects patient-specific plasticity on tumor cell behavior remain unclear. Here, multi-omics was used characterize microenvironment (TME) tumors patients undergoing...
Thyroid cancer progression from curable well-differentiated thyroid carcinoma to highly lethal anaplastic is distinguished by tumor cell de-differentiation and recruitment of a robust stromal infiltrate. Combining an integrated single-cell sequencing atlas with spatial transcriptomics bulk RNA-sequencing, we define subpopulations tumor-stromal cross-talk occurring across the histologic mutational spectrum cancer. We identify distinct inflammatory myofibroblastic cancer-associated fibroblast...
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