A5060082867- CRISPR and Genetic Engineering
- Genomics and Chromatin Dynamics
- Microtubule and mitosis dynamics
- Pluripotent Stem Cells Research
- Genetics and Neurodevelopmental Disorders
- Renal and related cancers
- RNA and protein synthesis mechanisms
- Animal Genetics and Reproduction
- RNA modifications and cancer
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Genetics, Aging, and Longevity in Model Organisms
- Advanced biosensing and bioanalysis techniques
- Chromatin Remodeling and Cancer
- Mechanisms of cancer metastasis
- Virus-based gene therapy research
- Monoclonal and Polyclonal Antibodies Research
- Cytomegalovirus and herpesvirus research
- RNA Research and Splicing
- Telomeres, Telomerase, and Senescence
- Developmental Biology and Gene Regulation
- Wnt/β-catenin signaling in development and cancer
- Genomic variations and chromosomal abnormalities
- Genetic and Kidney Cyst Diseases
- RNA Interference and Gene Delivery
- Epigenetics and DNA Methylation
University of Massachusetts Chan Medical School
2012-2023
Nuclease-directed genome editing is a powerful tool for investigating physiology and has great promise as therapeutic approach to correct mutations that cause disease. In its most precise form, can use cellular homology-directed repair (HDR) pathways insert information from an exogenously supplied DNA-repair template (donor) directly into targeted genomic location. Unfortunately, particularly long insertions, toxicity delivery considerations associated with DNA limit HDR efficacy. Here, we...
Recent advances using CRISPR-Cas9 approaches have dramatically enhanced the ease for genetic manipulation in rodents. Notwithstanding, methods to deliver nucleic acids into pre-implantation embryos hardly changed since original description of mouse transgenesis more than 30 years ago. Here we report a novel strategy generate genetically modified mice by transduction components via recombinant adeno-associated viruses (rAAVs). Using this approach, efficiently generated variety targeted...
Although histone-modifying enzymes are generally assumed to function in a manner dependent on their enzymatic activities, this assumption remains untested for many factors. Here, we show that the Tip60 (Kat5) lysine acetyltransferase (KAT), which is essential embryonic stem cell (ESC) self-renewal and pre-implantation development, performs these functions independently of its KAT activity. Unlike ESCs depleted Tip60, KAT-deficient exhibited minimal alterations gene expression, chromatin...
Brg1 (Brahma-related gene 1) is one of two mutually exclusive ATPases that can act as the catalytic subunit mammalian SWI/SNF (mSWI/SfigureNF) chromatin remodeling enzymes facilitate utilization DNA in eukaryotic cells. a phospho-protein, and its activity regulated by specific kinases phosphatases. Previously, we showed interacts with phosphorylated casein kinase 2 (CK2) manner regulates myoblast proliferation. Here, use biochemical cell molecular biology approaches to demonstrate Brg1-CK2...
Abstract Nuclease-directed genome editing is a powerful tool for investigating physiology and has great promise as therapeutic approach to correct mutations that cause disease. In its most precise form, can use cellular homology-directed repair (HDR) pathways insert information from an exogenously supplied DNA template (donor) directly into targeted genomic location. Unfortunately, particularly long insertions, toxicity delivery considerations associated with limit HDR efficacy. Here, we...
In female mice, the gene dosage from X chromosomes is adjusted by a process called chromosome inactivation (XCI) that occurs in two steps. An imprinted form of XCI (iXCI) silences paternally inherited (Xp) initiated at 2- to 4-cell stages. As extraembryonic cells including trophoblasts keep Xp silenced, epiblast give rise embryo proper reactivate and undergo random (rXCI) around implantation. Both iXCI rXCI require lncRNA Xist , which expressed be inactivated. The X-linked E3 ubiquitin...
ABSTRACT Brg1 (Brahma related gene 1) is one of two mutually exclusive ATPases that can act as the catalytic subunit mammalian SWI/SNF chromatin remodeling enzymes facilitate utilization DNA in eukaryotic cells. a phospho-protein and its activity regulated by specific kinases phosphatases. Previously, we showed interacts with phosphorylated casein kinase 2 (CK2) manner regulates myoblast proliferation. Here demonstrate Brg1-CK2 interaction occurred during mitosis embryonic somites primary...
Abstract Regulation of chromatin structure is critical for cell type-specific gene expression. Many regulatory complexes exist in several different forms, due to alternative splicing and differential incorporation accessory subunits. However, vivo studies often utilize mutations that eliminate multiple forms complexes, preventing assessment the specific roles each. Here we examined developmental TIP55 isoform KAT5 histone acetyltransferase. In contrast pre-implantation lethal phenotype mice...
Genetic engineering has become increasingly feasible with the advent of site-specific nucleases. This technology is highly effective for generation small mutations, however targeted insertion large sequences to generate transgenic animals remains challenging, time consuming, and laborious. Following several failed attempts using same reagents, we identified a protocol that achieved very high integration 3.2 kb transgene into single locus humanized mouse model Down syndrome. Moreover,...
Summary The period of development between the zygote and embryonic day 9.5 in mice includes multiple developmental milestones essential for embryogenesis. preeminence this has been illustrated loss function studies conducted by International Mouse Phenotyping Consortium (IMPC) which have shown that close to one third all mouse genes are survival weaning age a significant number mutations cause embryo lethality before E9.5. Here we report systematic analysis 21 pre-E9.5 lethal lines generated...
Cell proliferation and differentiation are tightly regulated processes required for the proper development of multi-cellular organisms. To understand effects cell on embryo patterning in mice, we inactivated Aurora A , a gene essential completion cycle. We discovered that inhibiting leads to different outcomes depending tissue affected. If epiblast, embryonic component, is compromised, it gastrulation failure. However, when extra-embryonic tissues, mutant embryos fail properly establish...
Summary In female mice the gene dosage from X chromosomes is adjusted by a process called chromosome inactivation (XCI) that occurs in two steps. An imprinted form of XCI (iXCI) silencing paternally inherited (Xp) initiated at 2-4 cell stages. As extraembryonic cells including trophoblasts keep Xp silenced, epiblast give rise to embryo proper reactivate and undergo random (rXCI) during peri-implantation Lack compensation leads lethality due inhibition trophoblast stem cells. However, as...