A5030116295- Genomics and Chromatin Dynamics
- Chromosomal and Genetic Variations
- RNA and protein synthesis mechanisms
- RNA Research and Splicing
- Fungal and yeast genetics research
- CRISPR and Genetic Engineering
- Cancer therapeutics and mechanisms
- Viral Infectious Diseases and Gene Expression in Insects
- Coastal wetland ecosystem dynamics
- Wastewater Treatment and Nitrogen Removal
- Microbial Community Ecology and Physiology
- Microtubule and mitosis dynamics
- DNA and Nucleic Acid Chemistry
- HIV/AIDS drug development and treatment
- Plant Virus Research Studies
- Gene expression and cancer classification
- Lipoproteins and Cardiovascular Health
- Genomics and Phylogenetic Studies
- Ubiquitin and proteasome pathways
- CAR-T cell therapy research
- HIV Research and Treatment
University of Massachusetts Chan Medical School
2020-2025
Howard Hughes Medical Institute
2016
University of Washington
2016
Fred Hutch Cancer Center
2016
Connecticut College
2013
The topological state of chromosomes determines their mechanical properties, dynamics, and function. Recent work indicated that interphase are largely free entanglements. Here, we use Hi-C, polymer simulations, multi-contact 3C find that, by contrast, mitotic self-entangled. We explore how a self-entangled is converted into an unentangled during exit. Most entanglements removed anaphase/telophase, with remaining ones early G1, in topoisomerase-II-dependent process. Polymer models suggest...
Epigenetic editing holds the promise of durable therapeutic effects by silencing disease-causing genes without changing underlying DNA sequence. In this study, we designed an epigenetic editor to target human PCSK9 and thereby induce methylation at locus. A single administration lipid nanoparticles encapsulating mRNA encoding was sufficient drive near-complete in transgenic mice. Silencing for least 1 year fully maintained after partial hepatectomy-induced liver regeneration. addition,...
The exclusive localization of the histone H3 variant CENP-A to centromeres is essential for accurate chromosome segregation. Ubiquitin-mediated proteolysis helps ensure that does not mislocalize euchromatin, which can lead genomic instability. Consistent with this, overexpression budding yeast CENP-A(Cse4) lethal in cells lacking Psh1, E3 ubiquitin ligase targets degradation. To identify additional mechanisms prevent misincorporation and lethality, we analyzed genome-wide mislocalization...
Since the discovery of ammonia-oxidizing archaea (AOA), new questions have arisen about population and community dynamics potential interactions between AOA Bacteria (AOB). We investigated effects long-term fertilization on AOB in Great Sippewissett Marsh, Falmouth, MA, USA to address some these questions. Sediment samples were collected from low high marsh habitats July 2009 replicate plots that received (LF), (HF), extra (XF) levels a mixed NPK fertilizer biweekly during growing season...
SUMMARY Despite the well-established role of nuclear organization in gene expression regulation, little is known about reverse: how transcription shapes spatial genome. Owing to small sizes most previously studied genes and limited resolution microscopy, structure arrangement a single transcribed are still poorly understood. Here, we make use several long highly expressed demonstrate that they form loops with polymerases moving along carrying nascent RNAs. Transcription can span across...
The incorporation of histone variants into nucleosomes can alter chromatin-based processes. CENP-A is the H3 variant found exclusively at centromeres that serves as an epigenetic mark for centromere identity and required kinetochore assembly. mislocalization to ectopic sites appears contribute genomic instability, transcriptional misregulation, tumorigenesis, so mechanisms exist ensure its exclusive localization centromeres. One conserved process proteolysis, which mediated by Psh1 E3...
Abstract Background Reducing the risk of atherosclerotic cardiovascular disease is dependent on both magnitude and cumulative duration LDL-C lowering. However, in clinical practice achieving treatment goals often hampered by low adherence to standard care. Although PCSK9 inhibitors represent an effective option for lowering, they require chronic life-long treatment. Epigenetic editing a new therapeutic approach designed durably silence genes leveraging nature’s endogenous cellular mechanism...
SUMMARY The topological state of chromosomes determines their mechanical properties, dynamics, and function. Recent work indicated that interphase are largely free entanglements. Here, we use Hi-C, polymer simulations multi-contact 3C, propose that, in contrast, mitotic self-entangled. We explore how a self-entangled is converted into an unentangled during exit. Most entanglements removed anaphase/telophase, with remaining ones early G1, Topoisomerase II-dependent process. Polymer models...