- Cell Image Analysis Techniques
- Endoplasmic Reticulum Stress and Disease
- RNA and protein synthesis mechanisms
- Biomedical Text Mining and Ontologies
- Molecular Biology Techniques and Applications
- Computational Drug Discovery Methods
- RNA Interference and Gene Delivery
- Bioinformatics and Genomic Networks
- Genetics, Bioinformatics, and Biomedical Research
- Advanced biosensing and bioanalysis techniques
- CRISPR and Genetic Engineering
- Ubiquitin and proteasome pathways
- RNA regulation and disease
- Gene expression and cancer classification
- Genetics, Aging, and Longevity in Model Organisms
- Cytomegalovirus and herpesvirus research
- Meta-analysis and systematic reviews
- Advanced Biosensing Techniques and Applications
- Cellular transport and secretion
- Health and Medical Research Impacts
- Doctoral Education Challenges and Solutions
- Fungal Biology and Applications
- Biosimilars and Bioanalytical Methods
- Reproductive Biology and Fertility
- Single-cell and spatial transcriptomics
Harvard University
2010-2024
Massachusetts Institute of Technology
2019-2020
University of California, San Francisco
1992-2020
New York University
2019-2020
University of California, Berkeley
2019-2020
Scripps Research Institute
2019-2020
Center for Systems Biology
2009-2017
Abdul Latif Jameel Poverty Action Lab
2014
MRC Laboratory of Molecular Biology
1992-1998
To make full use of research data, the bioscience community needs to adopt technologies and reward mechanisms that support interoperability promote growth an open 'data commoning' culture. Here we describe prerequisites for data commoning present established growing ecosystem solutions using shared 'Investigation-Study-Assay' framework vision.
Highlights•Implementing FAIR data standards requires identification of experimental confounders•Five labs performed the same experiment on mammalian cells and compared results•Several factors affecting reproducibility were explored•Biological context had an unexpected impact robustness cell-based assaysSummaryEvidence that some high-impact biomedical results cannot be repeated has stimulated interest in practices generate findable, accessible, interoperable, reusable (FAIR) data. Multiple...
The human cytomegalovirus protein, US11, initiates the destruction of MHC class I heavy chains by targeting them for dislocation from ER to cytosol and subsequent degradation proteasome. We report development a permeabilized cell system that recapitulates US11-dependent chains. have used this system, in combination with experiments intact cells, identify order intermediates pathway. find are ubiquitinated before they degraded. Ubiquitination cytosolic tail chain is not required its...
The National Institutes of Health Library Integrated Network-based Cellular Signatures (LINCS) program is generating extensive multidimensional data sets, including biochemical, genome-wide transcriptional, and phenotypic cellular response signatures to a variety small-molecule genetic perturbations with the goal creating sustainable, widely applicable, readily accessible systems biology knowledge resource. Integration analysis diverse LINCS sets depend on availability sufficient metadata...
The human cytomegalovirus protein US11 induces the dislocation of MHC class I heavy chains from endoplasmic reticulum (ER) into cytosol for degradation by proteasome. With use a fractionated, permeabilized cell system, we find that activity is needed only in membranes and additional cytosolic factors are required chain dislocation. We identify ubiquitin as one factors. Cytosol depleted does not support ER, can be restored adding back purified ubiquitin. Methylated-ubiquitin or mutant lacking...
RNA interference (RNAi) is an effective and important tool used to study gene function. For large-scale screens, RNAi systematically down-regulate genes of interest analyze their roles in a biological process. However, associated with off-target effects (OTEs), including microRNA (miRNA)-like OTEs. The contribution reagent-specific OTEs screen data sets can be significant. In addition, the post-screen validation process time labor intensive. Thus, availability robust approaches identify...
Detailed method descriptions are essential for reproducibility, research evaluation, and effective data reuse. We summarize the key recommendations life sciences researchers institutions described in European Commission PRO-MaP report.
The mTORC1 pathway is a central regulator of cell growth, and defective regulation plays causative role in variety human diseases, including cancer, tumor syndromes such as the tuberous sclerosis complex (TSC) lymphangioleiomyomatosis (LAM), metabolic diseases diabetes obesity. Given importance signaling these there has been significant interest developing screening methods suitable for identifying inhibitors activation. To this end, we have developed high-throughput, cell-based assay...
Shared-usage high throughput screening (HTS) facilities are becoming more common in academe as large-scale small molecule and genome-scale RNAi strategies adopted for basic research purposes. These shared require a unique informatics infrastructure that must not only provide access to analysis of data, but also manage the administrative technical challenges associated with conducting numerous, interleaved efforts run by multiple independent groups. We have developed Screensaver, free, open...
Detailed, accessible methods are essential for reproducibility, trust in science and scientific advancement; yet, many studies suggest that the reporting of methodological details life sciences research publications is often incomplete. This may be due to a lack incentives or standards, other cultural educational factors. Promoting Reusable Open Methods Protocols (PRO-MaP) aims increase improve detailed, reusable open step-by-step protocols sciences. initiative began with workshop convened...
Kinesin-5 (also known as Eg5, KSP and Kif11) is required for assembly of a bipolar mitotic spindle. Small molecule inhibitors Kinesin-5, developed potential anti-cancer drugs, arrest cell in mitosis promote apoptosis cancer cells. We performed genome-wide siRNA screen enhancers suppressors inhibitor human cells to elucidate cellular responses, thus identify factors that might predict drug sensitivity cancers. Because the drug's actions play out over several days, we an intermittent imaging...