A5070524317- Ocular Oncology and Treatments
- Multiple Myeloma Research and Treatments
- Protein Degradation and Inhibitors
- Cancer Genomics and Diagnostics
- CAR-T cell therapy research
- Immunotherapy and Immune Responses
- Ubiquitin and proteasome pathways
- Microtubule and mitosis dynamics
- PI3K/AKT/mTOR signaling in cancer
- Single-cell and spatial transcriptomics
- Pluripotent Stem Cells Research
- Chronic Lymphocytic Leukemia Research
- Cancer-related Molecular Pathways
- Retinal Development and Disorders
- Monoclonal and Polyclonal Antibodies Research
- Hippo pathway signaling and YAP/TAZ
- Epigenetics and DNA Methylation
- Peptidase Inhibition and Analysis
- Nanoplatforms for cancer theranostics
- Chronic Myeloid Leukemia Treatments
- Biochemical and Molecular Research
- Congenital heart defects research
- DNA Repair Mechanisms
- Synthesis and Biological Evaluation
- Advanced biosensing and bioanalysis techniques
Sylvester Comprehensive Cancer Center
2015-2024
University of Miami
2015-2024
Stem Cell Institute
2019
The California Eye Institute
2017
GSI Helmholtz Centre for Heavy Ion Research
2014
Technical University of Darmstadt
2014
Abstract Uveal melanoma (UM) is a highly metastatic cancer that, in contrast to cutaneous melanoma, largely unresponsive checkpoint immunotherapy. Here, we interrogate the tumor microenvironment at single-cell resolution using scRNA-seq of 59,915 and non-neoplastic cells from 8 primary 3 samples. Tumor reveal novel subclonal genomic complexity transcriptional states. Tumor-infiltrating immune comprise previously unrecognized diversity cell types, including CD8 + T predominantly expressing...
Cancer is thought to arise through the accumulation of genomic aberrations evolving under Darwinian selection. However, it remains unclear when associated with metastasis emerge during tumor evolution. Uveal melanoma (UM) most common primary eye cancer and frequently leads metastatic death, which strongly linked BAP1 mutations. Accordingly, UM ideally suited for studying clonal evolution competence. Here we analyze sequencing data from 151 samples using a customized bioinformatic pipeline,...
Abstract B cell maturation antigen (BCMA) target loss is considered to be a rare event that mediates multiple myeloma (MM) resistance anti-BCMA chimeric receptor T (CAR T) or bispecific engager (TCE) therapies. Emerging data report downregulation of G-protein-coupled family C group 5 member D (GPRC5D) protein often occurs at relapse after anti-GPRC5D CAR therapy. To examine the tumor-intrinsic factors promote MM escape, we performed combined bulk and single-cell whole-genome sequencing copy...
PURPOSE Outcomes for patients with newly diagnosed multiple myeloma (NDMM) are heterogenous, overall survival (OS) ranging from months to over 10 years. METHODS To decipher and predict the molecular clinical heterogeneity of NDMM, we assembled a series 1,933 available clinical, genomic, therapeutic data. RESULTS Leveraging comprehensive catalog genomic drivers, identified 12 groups, expanding on previous gene expression–based classifications. build model predicting individualized risk in...
p27 restrains normal cell growth, but PI3K-dependent C-terminal phosphorylation of at threonine 157 (T157) and T198 promotes cancer invasion. Here, we describe an oncogenic feedforward loop in which p27pT157pT198 binds Janus kinase 2 (JAK2) promoting STAT3 (signal transducer activator transcription 3) recruitment activation. induces TWIST1 to drive a p27-dependent epithelial-mesenchymal transition (EMT) further activates AKT contributing acquisition maintenance metastatic potential....
// Matthew G. Field 1 , Michael A. Durante Christina L. Decatur Bercin Tarlan Kristen M. Oelschlager 2 John F. Stone Jeffim Kuznetsov Anne Bowcock 3 Stefan Kurtenbach J. William Harbour Bascom Palmer Eye Institute, Sylvester Comprehensive Cancer Center and Interdisciplinary Stem Cell University of Miami Miller School Medicine, Miami, FL, USA Castle Biosciences, Inc., Friendswood, TX, National Heart Lung Imperial College London, UK Correspondence to: Harbour, email: harbour@miami.edu...
Abstract Glioblastoma (GBM) is the most common primary adult brain tumor. Despite extensive efforts, median survival for GBM patients approximately 14 months. therapy could benefit greatly from patient-specific targeted therapies that maximize treatment efficacy. Here we report a platform termed SynergySeq to identify drug combinations of by integrating information The Cancer Genome Atlas (TCGA) and Library Integrated Network-Based Cellular Signatures (LINCS). We differentially expressed...
Abstract Purpose: The clinical use of MEK inhibitors in uveal melanoma is limited by the rapid acquisition resistance. This study has used multiomics approaches and drug screens to identify pan-HDAC inhibitor panobinostat as an effective strategy limit Experimental Design: Mass spectrometry–based proteomics RNA-Seq were signaling pathways involved escape cells from therapy. Mechanistic studies performed evaluate identified, efficacy MEK-HDAC combination was demonstrated multiple vivo models...
Adoptive T cell therapy is a promising for multiple myeloma (MM), but its efficacy hinges on understanding relevant biological and predictive markers of response. B maturation antigen (BCMA) key target in MM, with active development anti-BCMA engagers (TCE) chimeric receptor (CAR T) therapies. The regulation surface BCMA expression by MM cells, resulting the shedding soluble (sBCMA), has triggered debate surrounding significance sBCMA as marker potential impact treatment outcomes. In order...
BAP1 regulates developmental switch in lineages commonly affected by BAP1-mutant cancers.
Abstract PRAME is a CUL2 ubiquitin ligase subunit that normally expressed in the testis but becomes aberrantly overexpressed many cancer types association with aneuploidy and metastasis. Here, we show predominantly spermatogonia around time of meiotic crossing-over coordination genes mediating DNA double strand break repair. Expression somatic cells upregulates pathways involved meiosis, chromosome segregation repair, it leads to increased breaks, telomere dysfunction neoplastic...
Abstract Background Recent advances in single cell sequencing technologies allow for greater resolution assessing tumor clonality using chromosome copy number variations (CNVs). While DNA are ideal to identify sub-clones, they remain expensive and contrast RNA-seq (scRNA-seq) methods more limited the data generate. However, CNV can be inferred from scRNA-seq bulk RNA-seq, which several tools have been developed, including inferCNV, CaSpER, HoneyBADGER. Inferences regarding (and other...
ABSTRACT Recent data highlight genomic events driving antigen escape as a recurring cause of chimeric receptor T-cell (CAR-T) and bispecific engager (TCE) resistance in multiple myeloma (MM). Yet, it remains unclear if these events, leading to clonal dominance at progression, result from acquisition under treatment selection or pre-existing undetectable clones. This differentiation gains importance immunotherapies progress earlier lines treatment, prompting the need for innovative diagnostic...
Retinoblastoma (Rb) is a deadly childhood eye cancer that classically initiated by inactivation of the RB1 tumor suppressor. Clinical management continues to rely on nonspecific chemotherapeutic agents are associated with treatment resistance and toxicity. Here, we analyzed 103 whole exomes, 20 transcriptomes, 5 single-cell 4 genomes from primary Rb tumors identify previously unknown dependencies. Several recurrent genomic aberrations implicate estrogen-related receptor gamma (ESRRG) in...
Early intervention for high-risk smoldering multiple myeloma (HR-SMM) achieves deep and prolonged responses. It is unclear if beneficial outcomes are due to the treatment of less complex, susceptible disease or inaccuracy in clinical definition cases entered.
Methods to detect DNA and RNA (collectively xNA) are easily plagued by noise, false positives, negatives, especially with increasing levels of multiplexing in complex assay mixtures. Here, we describe architectures that mitigate these problems converting standard xNA analyte sequences into incorporate nonstandard nucleotides (Z P). Z P extra building blocks form tight base pairs without cross-binding natural oligonucleotides containing G, A, C, T (GACT). The resulting improvements assessed...
Cells previously thought to mainly form nerves in the heart turn out be very important cardiac muscle formation.
Ocular melanocytosis is the most important predisposing condition for eye cancer uveal melanoma (UM). Here, we present a patient who developed UM arising within ocular was treated with enucleation (eye removal), which provided an invaluable opportunity to interrogate both and adjacent tissue containing using whole-exome deep-targeted sequencing. This analysis revealed clonal PLCB4 mutation in melanocytosis, confirming that this indeed neoplastic explaining why it predisposes UM. 100% of...
Uveal melanoma (UM) is the most common primary intraocular malignancy in adults and leads to deadly metastases for which there no approved treatment. Genetic events driving early tumor development are well-described, but those occurring later during metastatic progression remain poorly understood. We performed multiregional genomic sequencing on 22 tumors collected from two patients with widely UM who underwent rapid autopsy. observed multiple seeding tumors, metastasis-to-metastasis...