A5075684685- RNA Research and Splicing
- RNA and protein synthesis mechanisms
- RNA modifications and cancer
- Acute Myeloid Leukemia Research
- Bacterial Genetics and Biotechnology
- Genomics and Chromatin Dynamics
- Genomics and Phylogenetic Studies
- Viral Infectious Diseases and Gene Expression in Insects
- Epigenetics and DNA Methylation
- Bacteriophages and microbial interactions
- Molecular Junctions and Nanostructures
- Supramolecular Self-Assembly in Materials
- Porphyrin and Phthalocyanine Chemistry
- Protein Degradation and Inhibitors
- Acute Lymphoblastic Leukemia research
- Political Philosophy and Ethics
- Ethics and Legal Issues in Pediatric Healthcare
- Ubiquitin and proteasome pathways
- Immune Response and Inflammation
- Ethics in medical practice
- Philosophical Ethics and Theory
- Signaling Pathways in Disease
- Fungal and yeast genetics research
- RNA regulation and disease
- Philosophy and Theoretical Science
Massachusetts Institute of Technology
2016-2025
Harvard University
2023
Center for Systems Biology
2023
Memorial Sloan Kettering Cancer Center
2014-2021
Cornell University
2017
Haverford College
2013-2014
Johns Hopkins University
2003
The MUSASHI (MSI) family of RNA binding proteins (MSI1 and MSI2) contribute to a wide spectrum cancers including acute myeloid leukemia. We find that the small molecule Ro 08-2750 (Ro) binds directly selectively MSI2 competes for its in biochemical assays. treatment mouse human leukemia cells results an increase differentiation apoptosis, inhibition known MSI-targets, shared global gene expression signature similar shRNA depletion MSI2. demonstrates vivo c-MYC reduces disease burden murine...
Leukemia stem cells (LSCs) are found in most aggressive myeloid diseases and contribute to therapeutic resistance. exhibit a dysregulated developmental program as the result of genetic epigenetic alterations. Overexpression RNA-binding protein Musashi2 (MSI2) has been previously shown predict poor survival leukemia. Here, we demonstrated that conditional deletion Msi2 hematopoietic compartment results delayed leukemogenesis, reduced disease burden, loss LSC function murine leukemia model....
Abstract RNA endonucleases are the rate-limiting initiator of decay for many bacterial mRNAs. However, positions cleavage and their sequence determinants remain elusive even well-studied Bacillus subtilis. Here we present two complementary approaches—transcriptome-wide mapping endoribonucleolytic activity deep mutational scanning sites—that reveal distinct rules governing specificity among B. subtilis endoribonucleases. Detection terminal nucleotides in both 5′- 3′-exonuclease-deficient...
Somatic mutations that increase hematopoietic stem cell (HSC) fitness drive their expansion in clonal hematopoiesis (CH) and predispose to blood cancers. Although CH frequently occurs with aging, it rarely progresses overt malignancy. Population variation the growth rate potential of mutant clones suggests presence genetic factors protecting against CH, but these remain largely undefined. Here, we identify a non-coding regulatory variant, rs17834140-T, significantly protects myeloid...
Abstract Myelodysplastic syndromes (MDS) are driven by complex genetic and epigenetic alterations. The MSI2 RNA-binding protein has been demonstrated to have a role in acute myeloid leukaemia stem cell function, but its MDS is unknown. Here, we demonstrate that elevated expression correlates with poor survival MDS. Conditional deletion of Msi2 mouse model results rapid loss haematopoietic progenitor cells (HSPCs) reverses the clinical features Inversely, inducible overexpression drives...
ABSTRACT RNA endonucleases are the rate-limiting initiator of decay for many bacterial mRNAs. However, positions cleavage and their sequence determinants remain elusive even well-studied Bacillus subtilis . Here we present two complementary approaches – transcriptome-wide mapping endoribonucleolytic activity deep mutational scanning sites that reveal distinct rules governing specificity among B. endoribonucleases. Detection terminal nucleotides in both 5′- 3′-exonuclease-deficient cells...
Bacterial protein synthesis rates have evolved to maintain preferred stoichiometries at striking precision, from the components of complexes constituents entire pathways. Setting relative production be well within a factor two requires concerted tuning transcription, RNA turnover, and translation, allowing many potential regulatory strategies achieve output. The last decade has seen greatly expanded capacity for precise interrogation each step central dogma genome-wide. Here, we summarize...
The shelterin complex plays dual functions in telomere homeostasis by recruiting telomerase and preventing the activation of a DNA damage response at telomeric ends. Somatic stem cells require activity, as evidenced progressive cell loss leading to bone marrow failure hereditary dyskeratosis congenita. Recent work demonstrates that congenita can also arise from mutations specific genes, although little is known about somatic cells. We found mouse hematopoietic (HSCs) are acutely sensitive...
This study aims to extend a structural and biophysical understanding of coiled-coil based peptide model system that serves as scaffold for the anionic porphyrin, TPPS4. is part an ongoing biomaterials effort create photoelectronically active mesoscale fibrils surface deposition characterization conductivity properties. The goals are two-fold: (1) explore optimal basic side-chain moieties tight binding TPPS4 (2) test various metalated derivatives our system. latter goal control electronic...
SUMMARY The MUSASHI family of RNA binding proteins (MSI1 and MSI2) contribute to a wide spectrum cancers including acute myeloid leukemia. We found that the small molecule Ro 08–2750 (Ro) directly binds MSI2 competes for its in biochemical assays. treatment mouse human leukemia cells resulted an increase differentiation apoptosis, inhibition known MSI-targets, shared global gene expression signature similar shRNA depletion MSI2. demonstrated vivo c-MYC reduced disease burden murine AML...