A5090295818- RNA modifications and cancer
- Cancer Mechanisms and Therapy
- Cancer-related molecular mechanisms research
- Cancer, Hypoxia, and Metabolism
- Protein Tyrosine Phosphatases
- Molecular Biology Techniques and Applications
- CRISPR and Genetic Engineering
- Reproductive Health and Contraception
- Epigenetics and DNA Methylation
- Suicide and Self-Harm Studies
- Genomics and Chromatin Dynamics
- Chromatin Remodeling and Cancer
- Cancer Research and Treatments
- Ferroptosis and cancer prognosis
- Glycosylation and Glycoproteins Research
- Gene expression and cancer classification
- Peptidase Inhibition and Analysis
- Health disparities and outcomes
- Global Maternal and Child Health
- RNA Research and Splicing
- RNA Interference and Gene Delivery
- Maternal and Perinatal Health Interventions
- Homelessness and Social Issues
- Maternal and fetal healthcare
- Colorectal Cancer Treatments and Studies
Brown University
2023
University of Chicago Medical Center
2023
Broad Institute
2018-2022
Massachusetts Institute of Technology
2021
The availability of multiple datasets comprising genome-scale RNAi viability screens in hundreds diverse cancer cell lines presents new opportunities for understanding vulnerabilities. Integrated analyses these data to assess differential dependency across genes and are challenging due confounding factors such as batch effects variable screen quality, well difficulty assessing gene on an absolute scale. To address issues, we incorporated line screen-quality parameters hierarchical Bayesian...
Abstract We hypothesized that candidate dependencies for which there are small molecules either approved or in advanced development a nononcology indication may represent potential therapeutic targets. To test this hypothesis, we performed genome-scale loss-of-function screens hundreds of cancer cell lines. found knockout EGLN1, encodes prolyl hydroxylase domain-containing protein 2 (PHD2), reduced the proliferation subset clear ovarian lines vitro. EGLN1-dependent cells exhibited...
Gastroesophageal adenocarcinomas (GEAs) harbor recurrent amplification of KRAS, leading to marked overexpression WT KRAS protein. We previously demonstrated that SHP2 phosphatase, which acts promote and downstream MAPK pathway activation, is a target in these tumors when combined with MEK inhibition. hypothesized inhibitors may serve as foundation for developing novel combination inhibitor strategies therapy KRAS-amplified GEA, including targets outside the pathway. Here, we explore...
The availability of multiple datasets together comprising hundreds genome-scale RNAi viability screens across a diverse range cancer cell lines presents new opportunities for understanding vulnerabilities. Integrated analyses these data to assess differential dependency genes and are challenging due confounding factors such as batch effects variable screen quality, well difficulty assessing gene on an absolute scale. To address issues, we incorporated estimation line quality parameters...
Abstract Introduction Unhoused individuals have high rates of suicidal ideation (SI) and behaviors (SB), but few studied the relative timing homelessness SI/SB. Our study examines potential to use state‐wide electronic health record data from Rhode Island's information exchange (HIE) identify temporal relationships, service utilization, associations SI/SB among unhoused individuals. Methods We timestamped HIE for 5368 patients analyze utilization versus onset. Multivariable models identified...
<div>Abstract<p>We hypothesized that candidate dependencies for which there are small molecules either approved or in advanced development a nononcology indication may represent potential therapeutic targets. To test this hypothesis, we performed genome-scale loss-of-function screens hundreds of cancer cell lines. We found knockout <i>EGLN1</i>, encodes prolyl hydroxylase domain-containing protein 2 (PHD2), reduced the proliferation subset clear ovarian lines...
<p>Supplementary Figure 1 identifies EGLN1 as a cancer dependency in RNAi and CRISPR datasets contains all significant associations. Supplementary 2 is lineage analysis of within dataset. 3 an immunoblot showing knockout EGLN1-insensitive cell line. 4 shows pan-EGLN inhibition affects proliferation apoptosis. 5 specific inhibitor IOX2 VHL VH298 inhibit proliferation. 6 differentially expressed genes EGLN1-KO cells. 7 increased apoptosis vivo when inhibiting or VHL.</p>
<p>Supplementary Figure 1 identifies EGLN1 as a cancer dependency in RNAi and CRISPR datasets contains all significant associations. Supplementary 2 is lineage analysis of within dataset. 3 an immunoblot showing knockout EGLN1-insensitive cell line. 4 shows pan-EGLN inhibition affects proliferation apoptosis. 5 specific inhibitor IOX2 VHL VH298 inhibit proliferation. 6 differentially expressed genes EGLN1-KO cells. 7 increased apoptosis vivo when inhibiting or VHL.</p>
<div>Abstract<p>We hypothesized that candidate dependencies for which there are small molecules either approved or in advanced development a nononcology indication may represent potential therapeutic targets. To test this hypothesis, we performed genome-scale loss-of-function screens hundreds of cancer cell lines. We found knockout <i>EGLN1</i>, encodes prolyl hydroxylase domain-containing protein 2 (PHD2), reduced the proliferation subset clear ovarian lines...
Abstract Previously, we have used an integrated approach to use genome-scale screening in RNAi and CRISPR-Cas9 identify several putative cancer dependencies. From these dependencies, discovered EGLN1 was a significant selective dependency ovarian further enriched clear-cell cancers. Genetic knockout small-molecule inhibition of reduced cell proliferation increased apoptosis vitro vivo. We found the function as is through its canonical role negative HIF1A regulator HIF1A, but not HIF2A,...
Abstract Recent studies from the cancer genome atlas (TCGA. Nature. 2014) 2017) and other groups showed that a molecular subtype with chromosomal instability (CIN) is most common of gastroesophageal adenocarcinoma (GEA) characterized by aneuploidy without somatic hypermutation. The oncogene KRAS frequently amplified in CIN type gastric (14.3%) esophageal (10.4%). SHP2 phosphatase which part machinery activating GDP-bound inactive status to GTP-bound active status, our group previously...