A5048651737- Advanced Proteomics Techniques and Applications
- Genomics and Chromatin Dynamics
- Bioinformatics and Genomic Networks
- Biochemical and Molecular Research
- Single-cell and spatial transcriptomics
- RNA modifications and cancer
- RNA and protein synthesis mechanisms
- Phosphodiesterase function and regulation
- CRISPR and Genetic Engineering
- Genetics and Neurodevelopmental Disorders
- Cell Image Analysis Techniques
- Epigenetics and DNA Methylation
- Angiogenesis and VEGF in Cancer
- Telomeres, Telomerase, and Senescence
- Dendrimers and Hyperbranched Polymers
- Chronic Myeloid Leukemia Treatments
- Cardiovascular Disease and Adiposity
- Enzyme Structure and Function
- Chronic Lymphocytic Leukemia Research
- Luminescence and Fluorescent Materials
- Erythropoietin and Anemia Treatment
- Biomedical Text Mining and Ontologies
- Signaling Pathways in Disease
- Photochromic and Fluorescence Chemistry
- Ubiquitin and proteasome pathways
Broad Institute
2018-2025
Tufts University
2016-2017
Down syndrome (DS) is a genetic disorder driven by the triplication of chromosome 21 (T21) and characterized wide range neurodevelopmental physical disabilities. Transcriptomic analysis tissue samples from individuals with DS has revealed that T21 induces genome-wide transcriptional disruption. However, consequences on nuclear architecture its interplay transcriptome remain unknown. In this study, we find unlike human induced pluripotent stem cells (iPSCs), iPSC-derived neural progenitor...
Abstract DNMDP and related compounds, or velcrins, induce complex formation between the phosphodiesterase PDE3A SLFN12 protein, leading to a cytotoxic response in cancer cells that express elevated levels of both proteins. The mechanisms by which velcrins formation, how PDE3A-SLFN12 causes cell death, are not fully understood. Here, we show form heterotetramer stabilized binding DNMDP. Interactions C-terminal alpha helix residues near active site required for further interactions Moreover,...
Transcription and metabolism both influence cell function, but dedicated transcriptional control of metabolic pathways that regulate fate has rarely been defined. We discovered, using a chemical suppressor screen, inhibition the pyrimidine biosynthesis enzyme dihydroorotate dehydrogenase (DHODH) rescues erythroid differentiation in bloodless zebrafish moonshine (mon) mutant embryos defective for intermediary factor 1 gamma (tif1γ). This rescue depends on functional link DHODH to...
Abstract The phenotype of a cell and its underlying molecular state is strongly influenced by extracellular signals, including growth factors, hormones, matrix proteins. While these signals are normally tightly controlled, their dysregulation leads to phenotypic states associated with diverse diseases. To develop detailed understanding the linkage between changes, we generated comprehensive dataset that catalogs transcriptional, proteomic, epigenomic responses MCF10A mammary epithelial cells...
The Library of Integrated Network-based Cellular Signatures (LINCS), an NIH Common Fund program, has cataloged and analyzed cellular function molecular activity profiles in response to >80,000 perturbing agents that are potentially disruptive cells. Because the importance proteins their modifications specific perturbations, four six LINCS centers have included significant proteomics efforts characterization resulting phenotype. This manuscript aims describe this effort data harmonization...
Abstract Vascular endothelial growth factor receptor inhibitors (VEGFRis) improve cancer survival but are associated with treatment-limiting hypertension, often attributed to cell (EC) dysfunction. Using phosphoproteomic profiling of VEGFRi-treated ECs, drugs were screened for mitigators VEGFRi-induced EC dysfunction and validated in primary aortic mice, canine patients. VEGFRi treatment significantly raised systolic blood pressure (SBP) increased markers renal mice α-Adrenergic-antagonists...
Combining the numerous advantages of using light as a stimulus, simple free radical random copolymerization, and easy, all-aqueous preparation polyelectrolyte complexes (PECs), we prepared photolabile PEC nanoparticles demonstrated their rapid degradation under UV light. As proof concept demonstration, dye Nile Red was encapsulated in PECs successfully released into surrounding solution nanocomplex carriers dissolved upon irradiation.
We report a directly photopatternable polythiophene derivative PToNB with o-nitrobenzyl (oNB)-functionalized side chains. has unique phototunable solubilities programmed through three stages: (i) organic-soluble/aqueous-insoluble, (ii) organic-insoluble/aqueous-insoluble, and (iii) organic-insoluble/aqueous soluble. The capability to control conjugated polymer solubility spatiotemporal precision orthogonal developer solvents stages allows for direct patterning of this provides flexibility...
The N-terminal regions (tails) of histone proteins are dynamic elements that protrude from the nucleosome and involved in many aspects chromatin organization. Their epigenetic role is well-established, post-translational modifications present on these contribute to transcriptional regulation. Considering their biological significance, relatively few structural details have been established for tails, mainly because inherently disordered nature. Although hydrogen/deuterium exchange mass...
SUMMARY The phenotype of a cell and its underlying molecular state is strongly influenced by extracellular signals, including growth factors, hormones, matrix. While these signals are normally tightly controlled, their dysregulation leads to phenotypic states associated with diverse diseases. To develop detailed understanding the linkage between changes, we generated comprehensive dataset that catalogs transcriptional, proteomic, epigenomic responses MCF10A mammary epithelial cells after...
Introduction: Vascular endothelial growth factor receptor inhibitors (VEGFRis) are a class of tyrosine kinase (TKIs) used to treat human and canine cancers, but these drugs also cause hypertension (HTN) cell (EC) dysfunction. Purpose: We combined phosphoproteomic analysis in ECs with cross-species in-vitro in-vivo approach identify mitigating therapies for VEGFRi-induced EC dysfunction HTN. Methods Results: developed sorafenib-induced HTN mouse model showing increased blood pressure,...
Abstract The N-terminal regions of histone proteins (tails) are dynamic elements that protrude from the nucleosome and involved in many aspects chromatin organization. Their epigenetic role is well-established, post-translational modifications (PTMs) present on these contribute to transcriptional regulation. While hydrogen/deuterium exchange mass spectrometry (HX-MS) well-suited for analysis structures, it has seldom been employed analyze histones due poor coverage obtained using pepsin....
Abstract Understanding in-vivo mechanisms of erythropoiesis is critical for directed differentiation approaches to treat blood disorders such as leukemias. Zebrafish moonshine (mon) mutant embryos defective the conserved transcriptional intermediary factor 1 gamma (tif1γ) do not specify enough erythroid progenitors due a transcription elongation block characterized by aberrantly paused RNA polymerase II. To elucidate TIF1γ-mediated in differentiation, we performed chemical suppressor screen...
Abstract PDE3A-SLFN12 complex formation is induced by a class of compounds, now called “velcrins”, exemplified the small molecule, DNMDP. Cancer cells that express elevated levels PDE3A and SLFN12 are sensitive to velcrin-mediated cytotoxic response, which independent inhibition. However, details have not yet been revealed. We solved crystal structure with series ligands bound active site found exists as dimer, velcrin binding does cause any obvious structural changes in protein structure....