Kenneth Eagle
A5079788914- Acute Myeloid Leukemia Research
- RNA modifications and cancer
- DNA Repair Mechanisms
- CAR-T cell therapy research
- PARP inhibition in cancer therapy
- Immunodeficiency and Autoimmune Disorders
- Protein Degradation and Inhibitors
- Immune Cell Function and Interaction
- Advanced biosensing and bioanalysis techniques
- Genomics and Chromatin Dynamics
- GDF15 and Related Biomarkers
- Selenium in Biological Systems
- MicroRNA in disease regulation
- Digestive system and related health
- Ferroptosis and cancer prognosis
- Estrogen and related hormone effects
- Histone Deacetylase Inhibitors Research
- Nutrition, Genetics, and Disease
- Cancer, Hypoxia, and Metabolism
- Ubiquitin and proteasome pathways
- Advancements in Transdermal Drug Delivery
- Peroxisome Proliferator-Activated Receptors
- Surfactants and Colloidal Systems
- Glutathione Transferases and Polymorphisms
- Sperm and Testicular Function
Eagle Mount
2021-2024
Baylor College of Medicine
2019-2024
Dana-Farber/Boston Children's Cancer and Blood Disorders Center
2021-2023
Harvard University
2021-2023
Boston Children's Hospital
2021-2023
Dana-Farber Cancer Institute
2021-2023
University at Buffalo, State University of New York
1979
Acute myeloid leukemia with KMT2A (MLL) rearrangements is characterized by specific patterns of gene expression and enhancer architecture, implying unique core transcriptional regulatory circuitry. Here, we identified the transcription factors MEF2D IRF8 as selective dependencies KMT2A-rearranged AML, where displays partially redundant functions its paralog, MEF2C. Rapid factor degradation followed measurements genome-wide rates superresolution microscopy revealed that form a distinct module...
Abstract Relapse of acute myeloid leukemia (AML) after allogeneic bone marrow transplantation has been linked to immune evasion due reduced expression major histocompatibility complex class II (MHCII) genes through unknown mechanisms. In this work, we developed CORENODE, a computational algorithm for genome-wide transcription network decomposition that identified factor (TF) tetrad consisting IRF8, MYB, MEF2C, and MEIS1, regulating MHCII in AML cells. We show at relapse is transcriptionally...
Abstract Upregulation of MYC is a hallmark cancer, wherein drives oncogenic gene expression and elevates total RNA synthesis across cancer cell transcriptomes. Although this transcriptional anabolism fuels growth survival, the consequences metabolic stresses induced by excess cellular are poorly understood. Herein, we discover that degradation downstream ribonucleotide catabolism novel mechanism MYC-induced death. Combining genetics metabolomics, find increases decay through cytoplasmic...
Lineage-defining transcription factors form densely interconnected circuits in chromatin occupancy assays, but the functional significance of these networks remains underexplored. We reconstructed topology a leukemia cell network from direct gene-regulatory programs eight core transcriptional regulators established pre-steady state assays coupling targeted protein degradation with nascent transcriptomics. The displayed narrow, largely non-overlapping programs, forming sparsely hierarchy...
Attenuating aberrant transcriptional circuits holds great promise for the treatment of numerous diseases, including cancer. However, development inhibitors is hampered by lack a generally accepted functional cellular readout to characterize their target specificity and on-target activity. We benchmarked direct gene-regulatory signatures six agents reported as oncogenic transcription factor MYB against targeted degradation in nascent transcriptomics assay. The demonstrated partial genes but...
(1979). AN ANALYSIS OF DIFFUSION IN A MEDIUM CONTAINING DISPERSED REACTIVE CYLINDERS. Chemical Engineering Communications: Vol. 3, No. pp. 189-198.
Abstract The transcription factor PPARG is associated with the luminal lineage subtype representing ~65% of advanced urothelial cancer (UC) patients. Recurrent genetic alterations in PPARG, fibroblast growth receptor 3 (FGFR3), and heterodimeric binding partner for retinoid X alpha (RXRA), are characteristic this subtype. FX-909, a covalent inverse agonist, represents promising first-in-class therapy patients UC. FX-909-CLINPRO-1 [NCT05929235] an open-label Phase 1 study to evaluate safety,...
<div>Abstract<p>Upregulation of MYC is a hallmark cancer, wherein drives oncogenic gene expression and elevates total RNA synthesis across cancer cell transcriptomes. Although this transcriptional anabolism fuels growth survival, the consequences metabolic stresses induced by excess cellular are poorly understood. Herein, we discover that degradation downstream ribonucleotide catabolism novel mechanism MYC-induced death. Combining genetics metabolomics, find increases decay...
<div>Abstract<p>Upregulation of MYC is a hallmark cancer, wherein drives oncogenic gene expression and elevates total RNA synthesis across cancer cell transcriptomes. Although this transcriptional anabolism fuels growth survival, the consequences metabolic stresses induced by excess cellular are poorly understood. Herein, we discover that degradation downstream ribonucleotide catabolism novel mechanism MYC-induced death. Combining genetics metabolomics, find increases decay...
<p>Table S1 is the list of candidate facilitator genes MYC-induced cell death. Table lists facilitators death discovered through MYC-specific loss function genetic screen.</p>
<p>Figure S1 shows PCA of human breast tumors, hallmark MYC signature score for expression MYC-target NECTIN4, schematic purine ribonucleotide catabolism, concentrations nucleotides in physiological conditions, prediction hypothetical nucleotide flux, MYC-induced cell death MYC-ER HMECs, and candidate facilitators death.</p>
<p>Figure S4 shows DIS3L mutation in human tumors, evolutionary action score of tumor-derived DIS3L, genomic alteration MYC and breast cancer, expression mRNA genes ribonucleotide catabolism synthesis upon knockdown.</p>
<p>Figure S5 shows expression of MCL1 upon DIS3L knockdown, effect XDH inhibition on MYC-induced cell death, xanthosine TNBC apoptosis, ROS and death HPRT1 knockdown xenografts.</p>
<p>Figure S3 shows MYC-induced apoptosis and cell death in early late timepoints, ectopic expression of BCL2 its impact on RNA decay, gene changes upon DIS3L knockdown MYC-hyperactivated conditions, exosome components MYC-induction.</p>
<p>Table S2 shows gene ontology analysis of candidate facilitator genes MYC-induced cell death.</p>
<p>Figure S6 shows 6-mercaptopurine dose curve in various cell lines, effect of on purine catabolite abundance TNBC cells, XDH knockdown induced death, and 6-mercaptopurine- viability upon nucleotide supplementation.</p>
<p>Table S3 shows evolutionary Action analysis of tumor-derived mutation in DIS3L.</p>
<p>Table S4 shows predictions of hypothetical purine nucleotide flux.</p>
<p>Figure S2 shows MYC-induced cell death in MYC-ER HMECs with DIS3L, EXOSC2, EXOSC8 and DIS3 knockdown, expression of upon EU incorporation MYC-hyperactivated conditions.</p>
<p>Figure S4 shows DIS3L mutation in human tumors, evolutionary action score of tumor-derived DIS3L, genomic alteration MYC and breast cancer, expression mRNA genes ribonucleotide catabolism synthesis upon knockdown.</p>
<p>Table S1 is the list of candidate facilitator genes MYC-induced cell death. Table lists facilitators death discovered through MYC-specific loss function genetic screen.</p>
<p>Table S2 shows gene ontology analysis of candidate facilitator genes MYC-induced cell death.</p>