A5038984327- Ocular Oncology and Treatments
- Ubiquitin and proteasome pathways
- Immunotherapy and Immune Responses
- Epigenetics and DNA Methylation
- Microtubule and mitosis dynamics
- Nanoplatforms for cancer theranostics
- Robotic Mechanisms and Dynamics
- Manufacturing Process and Optimization
- Olfactory and Sensory Function Studies
- Protein Degradation and Inhibitors
- Histone Deacetylase Inhibitors Research
- Connexins and lens biology
- Cancer Genomics and Diagnostics
- Biochemical Analysis and Sensing Techniques
- Mechanical Engineering and Vibrations Research
- Robot Manipulation and Learning
- Single-cell and spatial transcriptomics
- Modular Robots and Swarm Intelligence
- Retinal Development and Disorders
- Flexible and Reconfigurable Manufacturing Systems
- Nicotinic Acetylcholine Receptors Study
- melanin and skin pigmentation
- Genomics and Phylogenetic Studies
- Neurobiology and Insect Physiology Research
- Design Education and Practice
University of Miami
2016-2025
Sylvester Comprehensive Cancer Center
2016-2025
The California Eye Institute
2017-2023
Stem Cell Institute
2023
The University of Texas Southwestern Medical Center
2022
University of Miami Health System
2021
York University
2013-2018
RWTH Aachen University
2011-2017
Ruhr University Bochum
2009-2017
Folkwang University of the Arts
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...
Uveal melanoma (UM) can be classified by gene expression profiling (GEP) into Class 1 (low metastatic risk) and 2 (high risk), the latter being strongly associated with mutational inactivation of tumor suppressor BAP1. Nevertheless, a small percentage tumors give rise to disease. The purpose this study was identify biomarkers metastasis in tumors.A total 389 consecutive patients UM were assigned or using prospectively validated 12-gene prognostic classifier. Selected further analyzed global...
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,...
Pannexin 1 (Panx1) represents a class of vertebrate membrane channels, bearing significant sequence homology with the invertebrate gap junction proteins, innexins and more distant similarities in topologies pharmacological sensitivities proteins connexin family. In nervous system, cooperation among pannexin adenosine receptors, KATP channels modulating neuronal excitability via ATP has been recognized, but little is known about significance vivo. However, localization Panx1 at postsynaptic...
// 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...
PURPOSEValidated and accurate prognostic testing is critical for precision medicine in uveal melanoma (UM). Our aims were to (1) prospectively validate an integrated classifier combining a 15-gene expression profile (15-GEP)
Calcium-activated chloride channels (CaCCs) are involved in many physiological processes, including sensory signal transduction, but only little is known to date about their structure and function. We performed a proteome analysis of the olfactory epithelium (OE) membrane identified so far uncharacterized proteins as candidate channels. One most abundant neurons (OSNs) was Tmem16b, member recently family CaCCs. In addition former studies on we show here that Tmem16b expression highly...
BAP1 regulates developmental switch in lineages commonly affected by BAP1-mutant cancers.
Abstract While there are sophisticated resources available for displaying NGS data, including the Integrative Genomics Viewer (IGV) and UCSC genome browser, exporting regions assembling figures publication remains challenging. In particular, customizing track appearance overlaying replicates is a manual time-consuming process. Here, we present SparK, tool which auto-generates publication-ready, high-resolution, true vector graphic from any NGS-based tracks, RNA-seq, ChIP-seq, ATAC-seq. Novel...
Abstract Purpose: The strong association between BAP1 mutations and metastasizing Class 2 uveal melanoma (UM) suggests that epigenetic alterations may play a significant role in tumor progression. Thus, we characterized the impact of loss on DNA methylome UM. Experimental Design: Global methylation was analyzed 47 1 45 primary UMs UM cells engineered to inducibly deplete BAP1. RNA-Seq 80 samples cells. Results: Hypermethylation chromosome 3 correlated with downregulated gene expression at...
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...
Uveal melanoma (UM) is the most common primary cancer of eye and associated with a high rate metastatic death. UM can be stratified into two main classes based on risk, class 1 having low risk 2 risk. Class have distinctive genomic, transcriptomic, histopathologic, clinical phenotype characterized by biallelic inactivation BAP1 tumor-suppressor gene, an immune-suppressive microenvironment enriched for M2-polarized macrophages, poor response to checkpoint-inhibitor immunotherapy. To identify...
Abstract Little is known about how interactions between the uveal melanoma (UM) and host cells in tumor microenvironment (TME) drive progression of liver metastases. Single cell RNA-seq analysis UM samples identified marked differences cell-cell communication primary metastatic characterized by increased signaling strength numbers emanating from hepatic stellate (HSCs) endothelial samples. In co-culture, HSCs modulated transcriptional heterogeneity cells, enriching for states that expressed...
Abstract Altered metabolism is a hallmark of cancer. Yet how metabolic reprogramming benefits tumor growth remains unclear. In retinoblastoma (RB), we have shown that estrogen-related receptor gamma (ESRRG) undergoes continuous positive selection during evolution as evidenced by an ongoing accumulation genomic aberrations increase ESRRG activity. Transcriptional analysis revealed pivotal in mediating reprogramming, with cells displaying preferential aerobic fermentation and microenvironment...
In mammals, a single pannexin1 gene (Panx1) is widely expressed in the CNS including inner and outer retinae, forming large-pore voltage-gated membrane channels, which are involved calcium ATP signaling. Previously, we discovered that zebrafish lack Panx1 expression retina, with drPanx1a exclusively horizontal cells of retina. Here, characterize second drPanx1 protein, drPanx1b, generated by whole-genome duplications during teleost evolution. Homology searches strongly support presence...