A5081241879- Epigenetics and DNA Methylation
- RNA modifications and cancer
- Cancer Genomics and Diagnostics
- Monoclonal and Polyclonal Antibodies Research
- Cancer-related gene regulation
- Cancer, Hypoxia, and Metabolism
- Cancer Immunotherapy and Biomarkers
- Cancer, Lipids, and Metabolism
- Radiopharmaceutical Chemistry and Applications
- Cancer-related molecular mechanisms research
- Single-cell and spatial transcriptomics
- CAR-T cell therapy research
- Pancreatic and Hepatic Oncology Research
- Prostate Cancer Treatment and Research
- CRISPR and Genetic Engineering
- Glycosylation and Glycoproteins Research
- Computational Drug Discovery Methods
- RNA Research and Splicing
- RNA and protein synthesis mechanisms
- Virus-based gene therapy research
- Protein Degradation and Inhibitors
- Lung Cancer Treatments and Mutations
- Cancer Research and Treatments
- Protease and Inhibitor Mechanisms
- Salivary Gland Disorders and Functions
Sidney Kimmel Comprehensive Cancer Center
2017-2025
Johns Hopkins University
2013-2025
Sidney Kimmel Cancer Center
2021-2025
Johns Hopkins Medicine
2013-2025
Cancer Genetics (United States)
2021-2025
University of Baltimore
2023-2024
Howard Hughes Medical Institute
2024
Cancer Research Center
2024
Broad Institute
2008
Dana-Farber Cancer Institute
2008
Oncogenic activation of tyrosine kinases is a common mechanism carcinogenesis and, given the druggable nature these enzymes, an attractive target for anticancer therapy. Here, we show that somatic mutations fibroblast growth factor receptor 2 (FGFR2) kinase gene, FGFR2 , are present in 12% endometrial carcinomas, with additional instances found lung squamous cell carcinoma and cervical carcinoma. These mutations, many which identical to associated congenital craniofacial developmental...
Inactivation of the tumor suppressor genes protein p53 ( TP53 ) and cyclin-dependent kinase inhibitor 2A CDKN2A occurs early during gastroesophageal junction (GEJ) tumorigenesis. However, because a paucity GEJ-specific disease models, cancer-promoting consequences inactivation at GEJ have not been characterized. Here, we report development wild-type primary human organoid model CRISPR-edited transformed model. CRISPR-Cas9–mediated knockout TP53/CDKN2A KO in organoids induced morphologic...
Two types of engineered T cells have been successfully used to treat patients with cancer, one an antigen recognition domain derived from antibodies [chimeric receptors (CARs)] and the other cell (TCRs). CARs use high-affinity antigen-binding domains costimulatory induce activation but can only react against target relatively high amounts antigen. TCRs a much lower affinity for their antigens displaying few molecules. Here, we describe new type receptor, called Co-STAR (for synthetic TCR...
A defining hallmark of primary and metastatic cancers is the migration invasion malignant cells. These invasive properties involve altered dynamics cytoskeleton one its major structural components β-actin. Here we identify AIM1 (absent in melanoma 1) as an actin-binding protein that suppresses pro-invasive benign prostate epithelium. Depletion epithelial cells increases cytoskeletal remodeling, intracellular traction forces, cell invasion, anchorage-independent growth. In addition, decreased...
Despite exciting developments in cancer immunotherapy, its broad application is limited by the paucity of targetable antigens on tumor cell surface. As an intrinsic cellular pathway, nonsense-mediated decay (NMD) conceals neoantigens through destruction RNA products from genes harboring truncating mutations. We developed and conducted a high-throughput screen, based ratiometric analysis transcripts, to identify critical mediators NMD human cells. This screen implicated disruption kinase...
Nearly 30% of pancreatic ductal adenocarcinomas (PDACs) exhibit a marked overexpression monocarboxylate transporter 1 (MCT1) offering unique opportunity for therapy. However, biochemical inhibitors MCT1 have proven unsuccessful in clinical trials. In this study, we present an alternative approach using 3-bromopyruvate (3BP) to target overexpressing PDACs. 3BP is cytotoxic agent that known be transported into cells via MCT1, but its usefulness has been hampered by difficulties delivering the...
Methylated DNA binding proteins such as Methyl-CpG Binding Domain Protein 2 (MBD2) can transduce methylation alterations into a repressive signal by recruiting transcriptional co-repressor complexes. Interfering with MBD2 could lead to reactivation of tumor suppressor genes and therefore represents an attractive strategy for epigenetic therapy. We developed compared fluorescence polarization (FP) time-resolved resonance energy transfer (TR-FRET)-based high-throughput screening (HTS) assays...
We describe the creation of an isogenic cell line panel representing common cancer pathways, with features optimized for high-throughput screening. More than 1,800 lines from three normal human were generated using CRISPR technologies. Surprisingly, most these did not result in complete gene inactivation despite integration sgRNA at desired genomic site. A subset harbored biallelic disruptions targeted tumor suppressor gene, yielding a final 100 well-characterized covering 19 frequently lost...
DNA methylation can mediate epigenetic silencing of tumor suppressor and cancer protective genes. The protein ubiquitin-like containing PHD ring finger domains 1 (UHRF1) is an essential component in cells for maintenance. SET- RING-associated (SRA) domain UHRF1 bind hemimethylated DNA, recruitment methyltransferases to copy the pattern newly synthesized daughter strand. Loss function lead demethylation re-expression epigenetically silenced genes reduce cell growth survival. We created a...
Abstract BACKGROUND The goal of the Prostate Cancer Biorepository Network (PCBN) is to develop a biorepository with high‐quality, well‐annotated specimens obtained in systematic, reproducible fashion using optimized and standardized protocols, an infrastructure facilitate growth resource its wide usage by prostate cancer research community. An emerging area concern field biobanking apparent shift proportion surgical procedures performed for treatment from radical retropubic prostatectomy...
Abstract Background Resistance to androgen deprivation therapies is a major driver of mortality in advanced prostate cancer. Therefore, there need develop new preclinical models that allow the investigation resistance mechanisms and assessment drugs for treatment castration‐resistant Methods We generated two novel cell line (LAPC4‐CR VCaP‐CR) which were derived by passaging LAPC4 VCaP cells vivo vitro under castrate conditions. performed detailed transcriptomic (RNA‐seq) proteomic analyses...
Summary Despite exciting developments in cancer immunotherapy, its broad application is limited by the paucity of targetable antigens on tumor cell surface. As an intrinsic cellular pathway, nonsense-mediated decay (NMD) conceals neoantigens through destruction RNA products from genes harboring truncating mutations. We developed and conducted a high throughput screen, based ratiometric analysis transcripts, to identify critical mediators NMD. This screen implicated disruption kinase SMG1’s...
Abstract DNA hypermethylation can trigger silencing of tumor suppressor genes during cancer development and progression, partly through binding by methylated-DNA proteins (MBD), such as MBD2, that function “epigenetic readers” recruit co-repressor complexes to promote gene repression. Inhibiting MBD2-mediated repression represents an attractive therapeutic strategy. Here, we used a cell-based screen identify small molecules capable reactivating hypermethylated promoter sequences. We...
Abstract Aberrant DNA methylation of gene promoters can be involved in silencing tumor suppressor genes cancer. The protein ubiquitin-like containing PHD and ring finger domains 1 (UHRF1) is an essential component the cellular machinery for maintenance couple other epigenetic histone modifications. UHRF1 thought to bind newly synthesized hemimethylated recruit methyltransferases copy pattern daughter strand. Interfering with ability methylated lead re-expression epigenetically silenced...
Abstract Mutation-associated neoantigens (MANAs) are exquisitely cancer-specific therapeutic targets. However, MANAs present at ultra-low densities on the cancer cell surface (as few as 1-2 copies per cell), leading to challenge of eliciting a sufficiently robust effect. We combined components both T receptors (TCRs) and chimeric antigen (CARs) create new receptor with improved potency against an ultra-low-density MANA. From CARs, we utilized antibody-based recognition domain (i.e. single...
Nearly 30% of Pancreatic ductal adenocarcinoma (PDAC)s exhibit a marked overexpression Monocarboxylate Transporter 1 (MCT1) offering unique opportunity for therapy. However, biochemical inhibitors MCT1 have proven unsuccessful in clinical trials. In this study we present an alternative approach using 3-Bromopyruvate (3BP) to target overexpressing PDACs. 3BP is cytotoxic agent that known be transported into cells via MCT1, but its usefulness has been hampered by difficulties delivering the...
Nearly 30% of Pancreatic ductal adenocarcinoma (PDAC)s exhibit a marked overexpression Monocarboxylate Transporter 1 (MCT1) offering unique opportunity for therapy. However, biochemical inhibitors MCT1 have proven unsuccessful in clinical trials. In this study we present an alternative approach using 3-Bromopyruvate (3BP) to target overexpressing PDACs. 3BP is cytotoxic agent that known be transported into cells via MCT1, but its usefulness has been hampered by difficulties delivering the...
Nearly 30% of pancreatic ductal adenocarcinomas (PDACs) exhibit a marked overexpression monocarboxylate transporter 1 (MCT1) offering unique opportunity for therapy. However, biochemical inhibitors MCT1 have proven unsuccessful in clinical trials. In this study, we present an alternative approach using 3-bromopyruvate (3BP) to target overexpressing PDACs. 3BP is cytotoxic agent that known be transported into cells via MCT1, but its usefulness has been hampered by difficulties delivering the...
Abstract Sialic acids have critical functions relating to host-pathogenic interactions and the immune microenvironment. Subsequent post-translational O-acetyl modifications add an extra layer of control by modulating many these in both normal transformed colorectal cells. The processes through which this modification is added sialic are not completely understood. To date only one gene, CASD1, has been identified encode a acid O-acetyltransferase human We used whole-genome sequencing on colon...
Abstract Despite exciting developments in cancer immunotherapy, its broad application is limited by the paucity of targetable antigens on tumor cell surface. As an intrinsic cellular pathway, nonsense-mediated decay (NMD) conceals neoantigens through destruction RNA products from genes harboring truncating mutations. We developed and conducted a high throughput screen, based ratiometric analysis transcripts, to identify critical mediators NMD. This screen revealed disruption kinase SMG1’s...