A5013677681- Cutaneous Melanoma Detection and Management
- CAR-T cell therapy research
- Melanoma and MAPK Pathways
- Cutaneous lymphoproliferative disorders research
- Polyomavirus and related diseases
- Immunotherapy and Immune Responses
- Nonmelanoma Skin Cancer Studies
- Lymphoma Diagnosis and Treatment
- Cancer Immunotherapy and Biomarkers
- Antenna Design and Analysis
- Full-Duplex Wireless Communications
- Bacteriophages and microbial interactions
- Plant Virus Research Studies
- Cancer and Skin Lesions
- Advanced Biosensing Techniques and Applications
- Cancer Genomics and Diagnostics
- Cervical Cancer and HPV Research
- Monoclonal and Polyclonal Antibodies Research
- Sarcoma Diagnosis and Treatment
- melanin and skin pigmentation
- Protein Tyrosine Phosphatases
- Computational Drug Discovery Methods
- Single-cell and spatial transcriptomics
- Optical Coherence Tomography Applications
- T-cell and B-cell Immunology
Moffitt Cancer Center
2016-2025
University of South Florida
2015-2024
University Medical Center Utrecht
2024
Florida College
2011-2023
Istituto Ortopedico Gaetano Pini
2022-2023
Brigham and Women's Hospital
2002-2022
Harvard University
2002-2022
University of California, San Francisco
2008-2022
Cleveland Clinic
2022
University of Pittsburgh Medical Center
2022
One mechanism contributing to immunologic unresponsiveness toward tumors may be presentation of tumor antigens by tolerogenic host APCs. We show that mouse tumor-draining LNs (TDLNs) contained a subset plasmacytoid DCs (pDCs) constitutively expressed immunosuppressive levels the enzyme indoleamine 2,3-dioxygenase (IDO). Despite comprising only 0.5% LN cells, these pDCs in vitro potently suppressed T cell responses presented themselves and also, dominant fashion, third-party nonsuppressive...
Gene-based immunotherapy for cancer is limited by the lack of safe, efficient, reproducible, and titratable delivery methods. Direct injection DNA into tissue, although safer than viral vectors, suffers from low gene transfer efficiency. In vivo electroporation, in preclinical models, significantly enhances efficiency while retaining safety advantages plasmid DNA.A phase I dose escalation trial interleukin (IL)-12 electroporation was carried out patients with metastatic melanoma. Patients...
This study addresses the role of PTEN loss in intrinsic resistance to BRAF inhibitor PLX4720. Immunohistochemical staining a tissue array covering all stages melanocytic neoplasia (n = 192) revealed expression be lost >10% melanoma cases. Although status did not predict for sensitivity growth inhibitory effects PLX4720, it was predictive apoptosis, with only limited cell death observed melanomas lacking (PTEN-). Mechanistically, PLX4720 found stimulate AKT signaling PTEN- but PTEN+ lines....
We have interrogated a 12-chemokine gene expression signature (GES) on genomic arrays of 14,492 distinct solid tumors and show broad distribution across different histologies. hypothesized that this GES might accurately predict unique intratumoral immune reaction in stage IV (non-locoregional) melanoma metastases. The predicted the presence unique, lymph node-like structures, containing CD20+ B cell follicles with prominent areas CD3+ T cells (both CD4+ CD8+ subsets). CD86+, but not FoxP3+,...
Resistance to BRAF inhibitors is an emerging problem in the melanoma field. Strategies prevent and overcome resistance are urgently required. The dynamics of cell signalling, BrdU incorporation cell-cycle entry after inhibition was measured using flow cytometry western blot. ability combined BRAF/MEK emergence demonstrated by apoptosis colony formation assays 3D organotypic culture. led a rapid recovery phospho-ERK (pERK) signalling. Although most cells remained growth arrested presence...
This selection from the NCCN Guidelines for Merkel Cell Carcinoma (MCC) focuses on areas impacted by recently emerging data, including sections describing MCC risk factors, diagnosis, workup, follow-up, and management of advanced disease with radiation systemic therapy. Included in these are discussion new recommendations use cell polyomavirus as a biomarker checkpoint immunotherapies to treat metastatic or unresectable disease. The next update complete version will include more detailed...
Most malignant peripheral nerve sheath tumors (MPNSTs) exhibit combined inactivation of NF1, CDKN2A, and polycomb repressive complex 2 component genes (Embryonic Ectoderm Development [EED] Suppressor Zeste 12 [SUZ12]). Mutations in EED SUZ12 induce loss trimethylation at lysine 27 histone 3 (H3K27me3), with subsequent aberrant transcriptional activation 2-repressed homeobox master regulators. These findings prompted us to investigate the performance an anti-H3K27me3 monoclonal antibody clone...
Indications for sentinel lymph node biopsy (SLNB) thin melanoma are continually evolving. We present a large multi-institutional study to determine factors predictive of (SLN) metastasis in melanoma.Retrospective review the Sentinel Lymph Node Working Group database from 1994 2012 identified 1,250 patients who had an SLNB and melanomas (≤ 1 mm). Clinicopathologic characteristics were correlated with SLN status outcome.SLN metastases detected 65 (5.2%) patients. On univariable analysis, rates...
Clinical trials have recently evaluated safety and efficacy of neoadjuvant therapy among patients with surgically resectable regional melanoma metastases. To capture informative prognostic data connected to pathological response in such trials, it is critical standardize pathologic assessment reporting tumor after this treatment.The International Neoadjuvant Melanoma Consortium meetings 2016 2017 assembled pathologists from academic centers develop consensus guidelines for examination...
Melanoma brain metastases (MBM) and leptomeningeal melanoma (LMM) are two different manifestations of CNS metastasis. Here, we used single-cell RNA sequencing (scRNA-seq) to define the immune landscape MBM, LMM, skin metastases.scRNA-seq was undertaken on 43 patient specimens, including 8 metastases, 14 19 serial LMM specimens. Detailed cell type curation performed, landscapes were mapped, key results validated by IHC flow cytometry. Association analyses identify subsets correlated with...
BACKGROUND Electroporation is a process that causes transient increase in the permeability of cell membranes. It can be used to intracellular concentration chemotherapeutic agents tumor cells (electrochemotherapy; ECT). A clinical study was initiated determine if this mode treatment would effective against certain primary and metastatic cutaneous malignancies. group six patients, three with malignant melanoma, two basal carcinoma, one adenocarcinoma, were enrolled study. The administered...
We produced capsids of Merkel cell polyomavirus (MCPyV) in a baculovirus expression system and developed virus-like particle (VLP) enzyme-linked immunosorbent assay (ELISA). To determine age-specific seroprevalence, serum samples were collected from 947 individuals attending hospital outpatient clinics ranging age 1 to 93 years. evaluate the association between exposure MCPyV cancer (MCC), plasma obtained 33 MCC patients 37 controls. seroprevalence was 45% children under 10 years age,...
Ca2+ signaling has been increasingly implicated in cancer invasion and metastasis, yet, the underlying mechanisms remained largely unknown. In this paper, we report that STIM1- Orai1-mediated oscillations promote melanoma by orchestrating invadopodium assembly extracellular matrix (ECM) degradation. oscillation signals facilitate invadopodial precursor activating Src. Disruption of inhibited assembly. Furthermore, STIM1 Orai1 regulate proteolysis activity individual invadopodia....
Histopathologic examination is sometimes inadequate for accurate and reproducible diagnosis of certain melanocytic neoplasms. As a result, more sophisticated objective methods have been sought. The goal this study was to identify gene expression signature that reliably differentiated benign malignant lesions evaluate its potential clinical applicability. Herein, we describe the development validation using multiple independent cohorts representing broad spectrum histopathologic...
Merkel cell carcinoma (MCC) is a rare, aggressive cutaneous malignancy, which has demonstrated sensitivity to immune checkpoint inhibitor therapy. Here, we perform the largest genomics study in MCC date characterize molecular landscape and evaluate for clinical correlates response.Comprehensive profiling was performed on 317 tumors from patients with MCC, including evaluation of oncogenic mutations, tumor mutational burden (TMB), signatures, polyomavirus (MCPyV). For subset 57 patients,...
[(99m)Tc]Tilmanocept is a CD206 receptor-targeted radiopharmaceutical designed for sentinel lymph node (SLN) identification. Two nearly identical nonrandomized phase III trials compared [(99m)Tc]tilmanocept to vital blue dye.Patients received and dye. SLNs identified intraoperatively as radioactive and/or were excised histologically examined. The primary end point, concordance, was the proportion of nodes detected by [(99m)Tc]tilmanocept; 90 % concordance prespecified minimum level. Reverse...