A5077374286- Ocular Oncology and Treatments
- Retinal Development and Disorders
- Ubiquitin and proteasome pathways
- Immunotherapy and Immune Responses
- Cancer-related Molecular Pathways
- Epigenetics and DNA Methylation
- Cutaneous Melanoma Detection and Management
- Histone Deacetylase Inhibitors Research
- Cancer Genomics and Diagnostics
- Microtubule and mitosis dynamics
- Chromatin Remodeling and Cancer
- Corneal Surgery and Treatments
- Retinal Diseases and Treatments
- Glaucoma and retinal disorders
- melanin and skin pigmentation
- Nanoplatforms for cancer theranostics
- Protein Degradation and Inhibitors
- Ocular Infections and Treatments
- CNS Lymphoma Diagnosis and Treatment
- Brain Metastases and Treatment
- Glioma Diagnosis and Treatment
- Hippo pathway signaling and YAP/TAZ
- Nonmelanoma Skin Cancer Studies
- Retinal and Macular Surgery
- interferon and immune responses
The University of Texas Southwestern Medical Center
2022-2025
Harold C. Simmons Comprehensive Cancer Center
2022-2025
Sylvester Comprehensive Cancer Center
2014-2023
University of Miami
2014-2023
The California Eye Institute
2017-2023
Southwestern Medical Center
2022-2023
Stem Cell Institute
2016-2023
University of Miami Health System
2021
Ophthalmology Associates (United States)
1996-2019
Washington University in St. Louis
2005-2019
An Eye on Metastasis Despite the considerable progress being made in elucidating cell biology of metastasis, little is known about genetic alterations that promote metastasis human tumors, cause most cancer deaths. A potentially important clue now emerges from work Harbour et al. (p. 1410 , published online 4 November), who used an exome-sequencing approach to search for mutations uveal melanomas, eye associated with a high rate fatal metastasis. Remarkably, over 80% tumor samples metastatic...
Small cell lung cancer (SCLC) has been associated with loss of heterozygosity at several distinct genetic loci including chromosomes 3p, 13q, and 17p. To determine whether the retinoblastoma gene ( Rb ) localized 13q14, might be target recessive mutations in cancer, eight primary SCLC tumors 50 lines representing all major histologic types were examined complementary DNA probe. Structural abnormalities within observed 1/8 (13%) tumors, 4/22 (18%) lines, 1/4 (25%) pulmonary carcinoid...
Abstract Melanomas are notoriously difficult to classify because of a lack discrete clinical and pathological stages. Here, we show that primary uveal melanomas surprisingly cluster into two distinct molecular classes based on gene expression profile. Genes discriminate class 1 (low-grade) from 2 (high-grade) include highly significant clusters down-regulated genes chromosome 3 up-regulated 8q, which is consistent with previous cytogenetic studies. A three-gene signature allows biopsy-size...
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...
Early/initiating oncogenic mutations have been identified for many cancers, but such remain unidentified in uveal melanoma (UM). An extensive search was undertaken, focusing on the RAF/MEK/ERK pathway, which is often target of initiating other types cancer.DNA samples from primary UMs were analyzed 24 potential oncogenes that affect pathway. For GNAQ, a stimulatory alpha(q) G-protein subunit recently found to be mutated UMs, resequencing expanded include 67 and 22 peripheral blood samples....
Metastasis is responsible for the death of most cancer patients, yet few therapeutic agents are available which specifically target molecular events that lead to metastasis. We recently showed inactivating mutations in tumor suppressor gene BAP1 closely associated with loss melanocytic differentiation uveal melanoma (UM) and The purpose this study was identify reverse phenotypic effects UM.In silico screens were done compounds predicted differentiate UM cells using Gene Set Enrichment...
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...
<h3>Importance</h3> Frequent mutations have been described in the following 5 genes uveal melanoma (UM):<i>BAP1</i>,<i>EIF1AX</i>,<i>GNA11</i>,<i>GNAQ</i>, and<i>SF3B1</i>. Understanding prognostic significance of these could facilitate their use precision medicine. <h3>Objective</h3> To determine associations between driver mutations, gene expression profile (GEP) classification, clinicopathologic features, and patient outcomes UM. <h3>Design, Setting, Participants</h3> Retrospective study...
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,...
Cell cycle exit is required for proper differentiation in most cells and critical normal development, tissue homeostasis, tumor suppression. However, the mechanisms that link cell with remain poorly understood. Here, we show master melanocyte factor, microphthalmia transcription factor (MITF), regulates by activating inhibitor INK4A, a suppressor frequently mutated melanomas. MITF binds INK4A promoter, activates p16Ink4a mRNA protein expression, induces retinoblastoma hypophosphorylation,...