Charlie Hatton
A5041491845- Protein Degradation and Inhibitors
- Acute Myeloid Leukemia Research
- Multiple Myeloma Research and Treatments
- Acute Lymphoblastic Leukemia research
- Histone Deacetylase Inhibitors Research
- Cancer-related gene regulation
- Lung Cancer Treatments and Mutations
- Cancer Genomics and Diagnostics
- Epigenetics and DNA Methylation
- Lymphoma Diagnosis and Treatment
- Click Chemistry and Applications
- Genomics and Chromatin Dynamics
- RNA modifications and cancer
- Genetics, Bioinformatics, and Biomedical Research
- Melanoma and MAPK Pathways
- RNA Interference and Gene Delivery
- Cancer Mechanisms and Therapy
- Molecular Biology Techniques and Applications
- CAR-T cell therapy research
- Chronic Lymphocytic Leukemia Research
- Chromatin Remodeling and Cancer
- Eosinophilic Disorders and Syndromes
- Lung Cancer Research Studies
- Computational Drug Discovery Methods
- HER2/EGFR in Cancer Research
Dana-Farber Cancer Institute
2012-2024
Boston Children's Hospital
2019-2024
Harvard University
2007-2023
Constellation Pharmaceuticals (United States)
2013-2016
TU Dortmund University
2011
Integrated Oncology (United States)
2011
Max Planck Society
2011
Max Planck Institute for Metabolism Research
2011
Broad Institute
2007-2011
Massachusetts Institute of Technology
2007-2011
Comprehensive knowledge of the genomic alterations that underlie cancer is a critical foundation for diagnostics, prognostics, and targeted therapeutics. Systematic efforts to analyze genomes are underway, but analysis hampered by lack statistical framework distinguish meaningful events from random background aberrations. Here we describe systematic method, called Genomic Identification Significant Targets in Cancer (GISTIC), designed analyzing chromosomal aberrations cancer. We use it study...
Genetic alterations that activate the mitogen-activated protein kinase (MAP kinase) pathway occur commonly in cancer. For example, majority of melanomas harbor mutations BRAF oncogene, which are predicted to confer enhanced sensitivity pharmacologic MAP inhibition (e.g., RAF or MEK inhibitors). We investigated clinical relevance dependency melanoma by massively parallel sequencing resistant clones generated from a MEK1 random mutagenesis screen vitro, as well tumors obtained relapsed...
The Alternative Lengthening of Telomeres (ALT) pathway is a telomerase-independent for telomere maintenance that active in significant subset human cancers and vitro immortalized cell lines. ALT thought to involve templated extension telomeres through homologous recombination, but the genetic or epigenetic changes unleash are not known. Recently, mutations ATRX/DAXX chromatin remodeling complex histone H3.3 were found correlate with features pancreatic neuroendocrine cancers, pediatric...
While genomically targeted therapies have improved outcomes for patients with lung adenocarcinoma, little is known about the genomic alterations which drive squamous cell cancer. Sanger sequencing of tyrosine kinome identified mutations in DDR2 kinase gene 3.8% cancers and lines. Squamous cancer lines harboring were selectively killed by knock-down RNAi or treatment multi-targeted inhibitor dasatinib. Tumors established from a mutant line sensitive to dasatinib xenograft models. Expression...
Detection of critical cancer gene mutations in clinical tumor specimens may predict patient outcomes and inform treatment options; however, high-throughput mutation profiling remains underdeveloped as a diagnostic approach. We report the implementation genotyping validation algorithm that enables robust setting.We developed implemented an optimized platform ("OncoMap") to interrogate approximately 400 33 known oncogenes suppressors, many which are response or resistance targeted therapies....
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...
Taking preventive measures Recent technological advances have made it possible to detect, in healthy individuals, premalignant blood cells that are likely progress hematologic cancer. These early detection fueled interest “cancer interception,” the idea drugs designed treat advanced cancer might also be useful for prevention. Uckelmann et al. now provide support this concept a study of mice genetically predisposed develop acute myeloid leukemia. Early administration an epigenetic therapy had...
Chromatin immunoprecipitation and DNA sequencing (ChIP-seq) has been instrumental in inferring the roles of histone post-translational modifications regulation transcription, chromatin compaction other cellular processes that require modulation structure. However, analysis ChIP-seq data is challenging when manipulation a chromatin-modifying enzyme significantly affects global levels modifications. For example, small molecule inhibition methyltransferase EZH2 reduces H3 lysine 27...
Pharmacological inhibition of chromatin co-regulatory factors represents a clinically validated strategy to modulate oncogenic signaling through selective attenuation gene expression. Here, we demonstrate that CBP/EP300 bromodomain preferentially abrogates the viability multiple myeloma cell lines. Selective targeting lines is result direct transcriptional suppression lymphocyte-specific transcription factor IRF4, which essential for cells, and concomitant repression IRF4 target c-MYC....
Lysine-specific demethylase 1 (KDM1A) is a transcriptional coregulator that can function in both the activation and repression of gene expression, depending upon context. KDM1A plays an important role hematopoiesis was identified as dependency factor leukemia stem cell populations. Therefore, we investigated consequences inhibiting panel lines representing all acute myelogenous (AML) subtypes using selective, reversible irreversible small-molecule inhibitors. Cell models AML, CML, T-ALL were...
Translocations involving the NUP98 gene produce NUP98-fusion proteins and are associated with a poor prognosis in acute myeloid leukemia (AML). MLL1 is molecular dependency leukemia, therefore we investigated efficacy of therapeutic blockade menin-MLL1 interaction models. Using mouse cell lines driven by NUP98-HOXA9 NUP98-JARID1A fusion oncoproteins, demonstrate that NUP98-fusion-driven sensitive to inhibitor VTP50469, an IC50 similar what have previously reported for MLL-rearranged NPM1c...
Ongoing cancer genome characterization studies continue to elucidate the spectrum of genomic abnormalities that drive many cancers, and in clinical arena assessment driver genetic alterations patients is playing an increasingly important diagnostic and/or prognostic role for types. However, landscape still unknown less common influence specific genotypes on behavior often unclear. To address some these deficiencies, we developed Profile, a prospective cohort study obtain information all at...
Abstract Purpose: The initiation, progression, and maintenance of pancreatic ductal adenocarcinoma (PDAC) results from the interplay genetic epigenetic events. While alterations PDAC have been well characterized, pathways regulating remain, for most part, elusive. goal this study was to identify novel regulators contributing biology PDAC. Experimental Design: In vivo pooled shRNA screens targeting 118 proteins were performed in two orthotopic xenograft models. Candidate genes characterized...