A5046839261- T-cell and B-cell Immunology
- Acute Myeloid Leukemia Research
- Lymphoma Diagnosis and Treatment
- Chronic Lymphocytic Leukemia Research
- Protein Degradation and Inhibitors
- Biotin and Related Studies
- Chronic Myeloid Leukemia Treatments
- Genomics and Chromatin Dynamics
- RNA modifications and cancer
- Acute Lymphoblastic Leukemia research
- Click Chemistry and Applications
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Monoclonal and Polyclonal Antibodies Research
- Cancer Immunotherapy and Biomarkers
- Single-cell and spatial transcriptomics
- Epigenetics and DNA Methylation
- Histone Deacetylase Inhibitors Research
- Protein Kinase Regulation and GTPase Signaling
- Ubiquitin and proteasome pathways
- Mycobacterium research and diagnosis
- Cancer-related gene regulation
- Immunodeficiency and Autoimmune Disorders
- Multiple Myeloma Research and Treatments
- Computational Drug Discovery Methods
- Retinoids in leukemia and cellular processes
Dana-Farber Cancer Institute
2019-2024
Harvard University
2019-2024
Boston Children's Hospital
2022-2024
Massachusetts General Hospital
2023
Johns Hopkins Medicine
2013-2021
Johns Hopkins University
2013-2021
Biotin-based labeling strategies are widely employed to study protein-protein interactions, subcellular proteomes and post-translational modifications, as well as, used in drug discovery. While the high affinity of streptavidin for biotin greatly facilitates capture biotinylated proteins, it still presents a challenge, currently employed, recovery peptides. Here we describe strategy designated Biotinylation Site Identification Technology (BioSITe) peptides LC-MS/MS analyses. We demonstrate...
Nuclear hormone receptors (NRs) are ligand-binding transcription factors that widely targeted therapeutically. Agonist binding triggers NR activation and subsequent degradation by unknown ligand-dependent ubiquitin ligase machinery. is critical for therapeutic efficacy in malignancies driven retinoic acid estrogen receptors. Here, we demonstrate the UBR5 drives of multiple agonist-bound NRs, including receptor alpha (RARA), retinoid x (RXRA), glucocorticoid, estrogen, liver-X, progesterone,...
The nuclear lamina is a proteinaceous network of filaments that provide both structural and gene regulatory functions by tethering proteins large domains DNA, the so-called lamina-associated (LADs), to periphery nucleus. LADs are fraction mammalian genome repressed, in part, their association periphery. genesis maintenance poorly understood as participate these functions. In an effort identify reside at potentially interact with LADs, we have taken two-pronged approach. First, undertaken...
Cellular function and diversity are orchestrated by complex interactions of fundamental biomolecules including DNA, RNA proteins. Technological advances in genomics, epigenomics, transcriptomics proteomics have enabled massively parallel unbiased measurements. Such high-throughput technologies been extensively used to carry out broad, studies, particularly the context human diseases. Nevertheless, a unified analysis genome, epigenome, transcriptome proteome single cell type obtain coherent...
Abstract Gastrointestinal stromal tumor (GIST) is commonly characterized by activating mutations in the receptor tyrosine kinase KIT. Tyrosine inhibitors are only approved therapy for GIST, and complementary treatment strategies urgently needed. As GIST lacks oncogene amplification relies upon an established network of transcription factors, we hypothesized that unique chromatin-modifying enzymes essential orchestrating epigenome. We identified through genome-scale CRISPR screening MOZ...
The direct targeting of chromatin-associated proteins is increasingly recognized as a potential therapeutic strategy for the treatment cancer. In this review, we discuss prominent example, namely, small-molecule inhibitors that target menin–KMT2A interaction. These molecules are currently being investigated in clinical trials and showing significant promise. We describe unique specificity protein complexes transcriptional regulation small subset genes drive developmental leukemic gene...
Abstract The menin-MLL1 interaction is critical for development of acute leukemias driven by MLL1 rearrangements (MLLr) or mutations in the Nucleophosmin 1 gene (NPM1c). Inhibition SNDX-5613 (revumenib) has demonstrated robust clinical responses current AUGMENT trial (NCT04065399). During trial, some responders relapsed during treatment due to acquired resistance MEN1. Somatic MEN1 were found at residues M327, G331 T349 which diminished SDNX-5613 binding affinity and mediated therapeutic...
Abstract Background: In patients with unexplained cytopenias, abnormal karyotyping studies can be found inconclusive light microscopic findings. Multidimensional flow cytometry (FCM) identify myelomonocytic cells aberrant phenotypes often not seen by standard morphology. Methods: 431 presenting cytopenia(s) FCM results were compared to and FISH recognized as associated myelodysplastic syndrome (MDS) in the 2008 WHO classification, assess degree of types phenotypic abnormalities observed...
The use of biotin or biotin-containing reagents is an essential component many protein purification and labeling technologies. Owing to its small size high affinity the avidin family proteins, a versatile molecular handle that permits both enrichment purity not easily achieved by other reagents. Traditionally, biotinylation enrich for proteins has required detection site biotinylation. However, newer technologies discovery protein-protein interactions, such as APEX BioID, well some click...
An increasingly common method for predicting gene activity is genome-wide chromatin immunoprecipitation of 'active' modifications followed by massively parallel sequencing (ChIP-seq).In order to understand better the relationship between developmentally regulated landscapes and regulation early B cell development, we determined how differentially active promoter regions were able predict relative RNA protein levels at pre-pro-B pro-B stages.Herein, describe a novel ChIP-seq quantification...
KRAS is one of the most frequently mutated genes across all cancer subtypes. Two frequent oncogenic mutations observed in patients result glycine to aspartic acid substitution at either codon 12 (G12D) or 13 (G13D). Although biochemical differences between these two predominant are not fully understood, distinct clinical features resulting tumors suggest involvement disparate signaling mechanisms. When we compared global phosphotyrosine proteomic profiles isogenic colorectal cell lines...
The GATA and PAX-SIX-EYA-DACH transcriptional networks (PSEDNs) are essential for proper development across taxa. Here, we demonstrate novel PSEDN roles in vivo Drosophila hematopoiesis human erythropoiesis vitro Using genetics, show that members function with to block lamellocyte differentiation maintain the prohemocyte pool. Overexpression of SIX1 stimulated erythroid erythroleukemia TF1 cells primary hematopoietic stem-progenitor cells. Conversely, knockout impaired both cell types....
Abstract The nuclear lamina is a proteinaceous network of filaments that provide both structural and gene regulatory functions by tethering proteins large domains DNA, so-called lamin associated (LADs), to the periphery nucleus. LADs are fraction mammalian genome repressed, in part, their association periphery. genesis maintenance poorly understood as participate these functions. In an effort identify reside at potentially interact with LADs, we have taken two-pronged approach. First,...