A5032474396- CRISPR and Genetic Engineering
- RNA Interference and Gene Delivery
- Genomics and Chromatin Dynamics
- RNA and protein synthesis mechanisms
- Advanced biosensing and bioanalysis techniques
- RNA modifications and cancer
- SARS-CoV-2 and COVID-19 Research
- Viral Infectious Diseases and Gene Expression in Insects
- Epigenetics and DNA Methylation
- CAR-T cell therapy research
- Plant Molecular Biology Research
- vaccines and immunoinformatics approaches
- Bacterial Genetics and Biotechnology
- Biochemical effects in animals
- Advanced Biosensing Techniques and Applications
- Cancer therapeutics and mechanisms
- Genetics, Bioinformatics, and Biomedical Research
- Vaccine Coverage and Hesitancy
- Biomedical and Engineering Education
- Bacteriophages and microbial interactions
- Histone Deacetylase Inhibitors Research
- Autophagy in Disease and Therapy
- Biochemical Analysis and Sensing Techniques
- Fuel Cells and Related Materials
- Cancer Immunotherapy and Biomarkers
Massachusetts Institute of Technology
2014-2018
University of California, Los Angeles
2008-2015
Harvard University
2011
Agilent Technologies (United States)
2011
DNA topoisomerases are believed to promote transcription by removing excessive supercoils produced during elongation. However, it is unclear how in eukaryotes recruited and function the pathway context of nucleosomes. To address this problem we present high-resolution genome-wide maps one major eukaryotic topoisomerases, Topoisomerase II (Top2) nucleosomes budding yeast, Saccharomyces cerevisiae . Our data indicate that at promoters Top2 binds primarily nucleosome-free. although nucleosome...
Yeast contains heterochromatin at telomeres and the silent mating-type loci (HML/HMR). Genes positioned within telomeric of Saccharomyces cerevisiae switch stochastically between epigenetically bistable ON OFF expression states. Important aspects mechanism variegated gene expression, including chromatin structure natural state by which it is maintained, are unknown. To address this issue, we developed approaches to select cells in We found immunoprecipitation (ChIP) that associated with Rap1...
Here we show that the Ino80 chromatin remodeling complex (Ino80C) directly prevents euchromatin from invading transcriptionally silent within intergenic regions and at border of heterochromatin. Deletion Ino80C subunits leads to increased H3K79 methylation noncoding RNA polymerase II (Pol II) transcription centered Ino80C-binding sites. The effect is direct, as it blocks by Dot1 in vitro. Heterochromatin stimulates binding vitro vivo. Our data reveal serves a general silencing restricts gene...
RNA replicons are an emerging platform for engineering synthetic biological systems. Replicons self-amplify, can provide persistent high-level expression of proteins even from a small initial dose, and, unlike DNA vectors, pose minimal risk chromosomal integration. However, no quantitative model sufficient levels protein such replicon systems currently exists. Here, we aim to enable the multigene more than one species by creating computational based on our experimental observations dynamics...
Synthetic mRNA therapeutics have the potential to revolutionize healthcare, as they enable patients produce therapeutic proteins inside their own bodies. However, convenient methods that allow external control over timing and magnitude of protein production after in vivo delivery synthetic are lacking. In this study, we validate utility a self-amplifying (RNA replicon) whose expression can be turned off using genetic switch responds oral administration trimethoprim (TMP), US Food Drug...
Histones of heterochromatin are deacetylated in yeast and methylated more complex eukaryotes to regulate structure gene silencing. Here, we report that histone H2A phosphorylated at serine 129 (γH2A) Saccharomyces cerevisiae is a conceptually new type modification functions downstream silent chromatin assembly. We show γH2A enriched throughout telomeric mating locus (HM) where results from the action kinases Tel1 Mec1. Interestingly, mutation has no apparent effect on binding Sir (silent...
TPS2696 Background: STX-001 is a multi-mechanistic lipid nanoparticle encapsulated synthetic self-replicating mRNA, engineered to express the IL-12 cytokine for an extended duration when administered intratumorally. A murine surrogate of induces deep durable responses in multiple preclinical solid tumor models. This Phase 1 open-label, multi-center first-in-human dose-escalation trial evaluates safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary antitumor...
<h3>Background</h3> Immunotherapies have revolutionized the treatment of solid tumors, which represent 90% adult human cancers. Therapeutic delivery IL-12, a potent immunostimulatory cytokine, is robustly effective in preclinical models. However, systemically delivered IL-12 poorly tolerated potentially due to its off-target activity. To overcome this challenge, we developed an mRNA platform that utilizes programmable genetic circuits regulate expression encoded protein based on specific...
The portfolio approach of financing drug development has been proposed as a financial innovation to improve the risk/return tradeoff investment in projects through use diversification and securitization. By investing sizable well-diversified novel candidates, issuing equity securitized debt based on this portfolio, performance such biomedical "megafund" can be made attractive wide group investors private sector. To analyze viability expediting vaccine against emerging infectious diseases, we...
The COVID-19 pandemic has raised awareness about the global imperative to develop and stockpile vaccines against future outbreaks of emerging infectious diseases (EIDs). Prior pandemic, vaccine development for EIDs was stagnant, largely due lack financial incentives pharmaceutical firms invest in research (R&D). This R&D requires significant capital investment, most notably conducting clinical trials, but generate much less profit compared with other therapeutics disease areas such as...
Abstract Critical advances in immunotherapies have expanded treatment options and improved patient outcomes across many solid tumor indications. However, durable clinical responses conferred by such as immune checkpoint inhibitors are experienced only a minority of patients, part because these therapies fail to sufficiently activate recruit T cells into the tumor. Therapeutic use cytokines potently stimulate tumor-reactive shown great promise treating tumors but narrow therapeutic index has...