A5026065236- Acute Myeloid Leukemia Research
- Protein Degradation and Inhibitors
- Multiple Myeloma Research and Treatments
- Epigenetics and DNA Methylation
- Renal and related cancers
- Genomics and Chromatin Dynamics
- RNA modifications and cancer
- Synthetic Organic Chemistry Methods
- Advanced biosensing and bioanalysis techniques
- CAR-T cell therapy research
- MicroRNA in disease regulation
- Caveolin-1 and cellular processes
- Immune cells in cancer
- Genetic Syndromes and Imprinting
- Cancer, Lipids, and Metabolism
- Ubiquitin and proteasome pathways
- Acute Lymphoblastic Leukemia research
- Cancer-related Molecular Pathways
- Cancer-related gene regulation
- CRISPR and Genetic Engineering
- Cholesterol and Lipid Metabolism
- Phagocytosis and Immune Regulation
Allen Institute
2025
Massachusetts Institute of Technology
2014-2025
Koch Institute for Integrative Cancer Research At MIT
2023
Rockefeller University
2018-2023
Abstract Menin interacts with oncogenic MLL1-fusion proteins, and small molecules that disrupt these associations are in clinical trials for leukemia treatment. By integrating chromatin-focused genome-wide CRISPR screens genetic, pharmacologic, biochemical approaches, we discovered a conserved molecular switch between the MLL1–Menin MLL3/4–UTX chromatin-modifying complexes dictates response to Menin–MLL inhibitors. safeguards survival by impeding binding of complex at subset target gene...
We performed a genome-scale shRNA screen for modulators of B-cell leukemia progression in vivo. Results from this work revealed dramatic distinctions between the relative effects shRNAs on growth tumor cells culture versus their native microenvironment. Specifically, we identified many “context-specific” regulators development. These included gene encoding zinc finger protein Phf6. While inactivating mutations PHF6 are commonly observed human myeloid and T-cell malignancies, found that Phf6...
Significance Diffuse intrinsic pontine glioma (DIPG) is an incurable childhood cancer with a median survival of less than 1 y. Characterization druggable targets in this disease remains longstanding goal, as no pharmacological agents have proven efficacy malignancy. We recently identified the menin inhibitor, MI-2, exhibiting potent antitumor activity preclinical models DIPG. Here, we show that MI-2 exerts its largely independent ability to target epigenetic regulator menin, but instead by...
Abstract Polycomb group proteins maintain gene expression patterns established during early development, with Repressive Complex 2 (PRC2) methyltransferase a key regulator of cell differentiation, identity and plasticity. Consequently, extensive somatic mutations in PRC2, including gain- or loss- function (GOF LOF), are observed human cancers. The regulation chromatin structure by PRC2 is critically dependent on its EZH2 (Enhancer Zeste Homolog 2) subunit, which catalyzes the methylation...
Aging is associated with a decline in the number and fitness of adult stem cells
Mutations in genes encoding components of chromatin modifying and remodeling complexes are among the most frequently observed somatic events human cancers. For example, missense nonsense mutations targeting mixed lineage leukemia family member 3 (MLL3, encoded by KMT2C) histone methyltransferase occur a range solid tumors, heterozygous deletions encompassing KMT2C subset aggressive leukemias. Although MLL3 loss can promote tumorigenesis mice, molecular targets biological processes which...
Abstract In the ever evolving field of functional genomics, CRISPR-based screening technologies have become pivotal tools for elucidating gene function across various cell types. A recent study by Gilan and colleagues advances this technological frontier introducing CRISPR-ChIP, a platform designed to investigate complex dynamics epigenetic regulation chromatin. proof-of-concept experiments, authors demonstrate potential tool identify key molecular regulators two major histone modifications...
<div>Abstract<p>Menin interacts with oncogenic MLL1-fusion proteins, and small molecules that disrupt these associations are in clinical trials for leukemia treatment. By integrating chromatin-focused genome-wide CRISPR screens genetic, pharmacologic, biochemical approaches, we discovered a conserved molecular switch between the MLL1–Menin MLL3/4–UTX chromatin-modifying complexes dictates response to Menin–MLL inhibitors. safeguards survival by impeding binding of complex at...
<div>Abstract<p>Menin interacts with oncogenic MLL1-fusion proteins, and small molecules that disrupt these associations are in clinical trials for leukemia treatment. By integrating chromatin-focused genome-wide CRISPR screens genetic, pharmacologic, biochemical approaches, we discovered a conserved molecular switch between the MLL1–Menin MLL3/4–UTX chromatin-modifying complexes dictates response to Menin–MLL inhibitors. safeguards survival by impeding binding of complex at...
<p>Supplementary Figures S1-S25</p>
<p>Supplementary Figures S1-S25</p>