A5089753578- Neuroblastoma Research and Treatments
- Protein Degradation and Inhibitors
- Bacterial Identification and Susceptibility Testing
- Virus-based gene therapy research
- RNA and protein synthesis mechanisms
- Infective Endocarditis Diagnosis and Management
- RNA modifications and cancer
- RNA Research and Splicing
- Salmonella and Campylobacter epidemiology
- Genomics and Phylogenetic Studies
- DNA Repair Mechanisms
- CRISPR and Genetic Engineering
- Genetics and Neurodevelopmental Disorders
- Genomics and Chromatin Dynamics
- Ubiquitin and proteasome pathways
Harvard University
2022-2024
Dana-Farber Cancer Institute
2022-2024
University of California, Berkeley
2015-2023
Boston Children's Hospital
2022
According to World Health Organization statistics of 2011, infectious diseases remain in the top five causes mortality worldwide. However, despite sophisticated research tools for microbial detection, rapid and accurate molecular diagnostics identification infection humans have not been extensively adopted. Time-consuming culture-based methods forefront clinical detection. The 16S rRNA gene, a marker bacterial species, is ubiquitous members this domain and, thanks ever-expanding databases...
The transcription-associated cyclin dependent kinases (CDKs) 12 and 13 play important roles in the expression of RNAs involved DNA damage repair ribosomal proteins, yet their if any, regulation are unclear. Here we show that these CDKs critical processing degradation noncoding nucleolus inhibition function leads to upregulation unprocessed RNA (rRNA) transcripts intergenic spacer (IGS) regions between subunits. These upregulated aberrantly polyadenylated by TRAMP complex polymerase TENT4,...
Cyclin-dependent kinases (CDKs) that have critical roles in RNA polymerase II (Pol II)-mediated gene transcription are emerging as therapeutic targets cancer. We previously shown THZ1, a covalent inhibitor of CDKs 7/12/13, leads to cytotoxicity MYCN-amplified neuroblastoma through the downregulation super-enhancer-associated transcriptional upregulation. Here we determined effects YKL-5-124, novel with greater selectivity for CDK7 cells.We tested YKL-5-124 and nonamplified cells individually...
Tumor MYCN amplification is seen in high-risk neuroblastoma, yet direct targeting of this oncogenic transcription factor has been challenging. Here, we take advantage the dependence MYCN-amplified neuroblastoma cells on increased protein synthesis to inhibit activity eukaryotic translation initiation 4A1 (eIF4A1) using an amidino-rocaglate, CMLD012824. Consistent with role RNA helicase resolving structural barriers 5' untranslated regions (UTRs), CMLD012824 eIF4A1 affinity for...
Abstract Tumor cell amplification of the MYCN transcription factor is seen in half patients with high-risk neuroblastoma, where it functions as an oncogenic driver associated metastatic disease and poor survival. Yet, direct targeting has been met little success, prompting efforts to inhibit its expression at multiple levels. MYCN-amplified neuroblastoma cells have increased requirement for protein synthesis meet overwhelming transcriptional burden imposed by MYCN. Here, we take advantage...
Improper regulation of translation initiation, a vital checkpoint protein synthesis in the cell, has been linked to number cancers. Overexpression subunits eukaryotic initiation factor 3 (eIF3) is associated with increased mRNAs involved cell proliferation. In addition playing major role general by serving as scaffold for assembly complexes, eIF3 regulates specific cellular and viral RNAs. Mutations N-terminal Helix-Loop-Helix (HLH) RNA-binding motif EIF3A subunit interfere Hepatitis C Virus...
ABSTRACT Improper regulation of translation initiation, a vital checkpoint protein synthesis in the cell, has been linked to number cancers. Overexpression subunits eukaryotic initiation factor 3 (eIF3) is associated with increased mRNAs involved cell proliferation. In addition playing major role general by serving as scaffold for assembly complexes, eIF3 regulates specific cellular and viral RNAs. Mutations N-terminal Helix-Loop-Helix (HLH) RNA-binding motif EIF3A subunit interfere...