A5020717652- CAR-T cell therapy research
- Immunotherapy and Immune Responses
- Ubiquitin and proteasome pathways
- CRISPR and Genetic Engineering
- Epigenetics and DNA Methylation
- Gene expression and cancer classification
- Genetics, Bioinformatics, and Biomedical Research
- Telomeres, Telomerase, and Senescence
- Advanced biosensing and bioanalysis techniques
- RNA Interference and Gene Delivery
- Autophagy in Disease and Therapy
- Microtubule and mitosis dynamics
- Bioinformatics and Genomic Networks
- Protein Degradation and Inhibitors
- HIV Research and Treatment
- vaccines and immunoinformatics approaches
- Cancer-related gene regulation
- SARS-CoV-2 and COVID-19 Research
- Molecular Biology Techniques and Applications
- RNA modifications and cancer
- Cancer-related Molecular Pathways
- Endoplasmic Reticulum Stress and Disease
- Genomics and Phylogenetic Studies
- Peptidase Inhibition and Analysis
- Cellular Mechanics and Interactions
Howard Hughes Medical Institute
2011-2024
Brigham and Women's Hospital
2012-2024
Harvard University
2012-2024
TScan Therapeutics (United States)
2020-2023
Dana-Farber Cancer Institute
2012
Massachusetts General Hospital
2008
Cold Spring Harbor Laboratory
2008
Baylor College of Medicine
2004-2006
Institute of Molecular Biology and Biophysics
2004-2006
University of Tsukuba
2004
Cellular senescence is a terminal stress-activated program controlled by the p53 and p16(INK4a) tumor suppressor proteins. A striking feature of senescence-associated secretory phenotype (SASP), pro-inflammatory response linked to promotion aging. We have identified transcription factor GATA4 as SASP regulator. stabilized in cells undergoing required for SASP. Normally, degraded p62-mediated selective autophagy, but this regulation suppressed during senescence, thereby stabilizing GATA4....
The abundance of cellular proteins is determined largely by the rate transcription and translation coupled with stability individual proteins. Although we know a great deal about global transcript abundance, little known protein stability. We present highly parallel multiplexing strategy to monitor turnover on scale coupling flow cytometry microarray technology track within complex mixture. demonstrated feasibility this approach measuring approximately 8000 human identifying proteasome...
The human virome plays important roles in health and immunity. However, current methods for detecting viral infections antiviral responses have limited throughput coverage. Here, we present VirScan, a high-throughput method to comprehensively analyze antibodies using immunoprecipitation massively parallel DNA sequencing of bacteriophage library displaying proteome-wide peptides from all viruses. We assayed over 10(8) antibody-peptide interactions 569 humans across four continents, nearly...
Myc is an oncogenic transcription factor frequently dysregulated in human cancer. To identify pathways supporting the program, we used a genome-wide RNA interference screen to search for Myc-synthetic lethal genes and uncovered role SUMO-activating enzyme (SAE1/2). Loss of SAE1/2 enzymatic activity drives synthetic lethality with Myc. Inactivation SAE2 leads mitotic catastrophe cell death upon hyperactivation. Mechanistically, inhibition switches transcriptional subprogram from activated...
Retroviral short hairpin RNA (shRNA)-mediated genetic screens in mammalian cells are powerful tools for discovering loss-of-function phenotypes. We describe a highly parallel multiplex methodology screening large pools of shRNAs using half-hairpin barcodes microarray deconvolution. carried out dropout that affect cell proliferation and viability cancer normal cells. identified many to be antiproliferative target core cellular processes, such as the cycle protein translation, all examined....
We performed a genome-wide siRNA screen in mouse embryonic stem (ES) cells to identify genes essential for self-renewal, and found 148 whose down-regulation caused differentiation. Many of the identified function gene regulation and/or development, are highly expressed ES tissues. further target two transcription regulators Cnot3 Trim28. discovered that Trim28 co-occupy many putative promoters with c-Myc Zfx, but not other pluripotency-associated factors. They form unique module self-renewal...
Cancer Gene Islands Human tumors are riddled with genomic alterations that rearrange, remove, amplify, or otherwise disrupt a wide spectrum of genes, and key challenge is identifying which these causally involved in tumorigenesis. The role recurrent hemizygous focal deletions especially puzzling because preferentially affect certain chromosomal regions result the loss one copy whole cluster adjacent genes. Solimini et al. (p. 104 , published online 24 May; see Perspective by Greenman ) found...
DNA barcodes linked to genetic features greatly facilitate screening these in pooled formats using microarray hybridization, and new tools are needed design large sets of allow construction barcoded mammalian libraries such as shRNA libraries. Here we report a framework for designing orthogonal barcode probes. We demonstrate the utility this by 240,000 probes testing their performance hybridization. From test hybridizations, also discovered probe rules that significantly reduce...
Scleroderma is a chronic autoimmune rheumatic disease associated with widespread tissue fibrosis and vasculopathy. Approximately two-thirds of all patients scleroderma present three dominant autoantibody subsets. Here, we used pair complementary high-throughput methods for antibody epitope discovery to examine or without known specificities. We identified specificity the minor spliceosome complex containing RNA Binding Region (RNP1, recognition motif) Containing 3 (RNPC3) that found in...
Abstract Summary: Visual programming offers an intuitive means of combining known analysis and visualization methods into powerful applications. The system presented here enables users who are not programmers to manage microarray genomic data flow customize their analyses by common tools fit needs. Availability: http://www.ailab.si/supp/bi-visprog Contact: blaz.zupan@fri.uni-lj.si Supplementary information:
Abstract Genetic screens are invaluable tools for dissection of biological phenomena. Optimization such to enhance discovery candidate genes and minimize false positives is thus a critical aim. Here, we report several sources error common pooled genetic screening techniques used in mammalian cell culture systems, demonstrate methods eliminate these errors. We find that reverse transcriptase-mediated recombination during retroviral replication can lead uncoupling molecular tags, as DNA...
A large number of cancer drivers have been identified through tumor sequencing efforts, but how they interact and the degree to which can substitute for each other not systematically explored. To comprehensively investigate genetically interact, we searched modifiers epidermal growth factor receptor (EGFR) dependency by performing CRISPR, shRNA, expression screens in a non-small cell lung (NSCLC) model. We elucidated broad spectrum suppressor genes (TSGs) oncogenes (OGs) that modify...
We explore the landscape of a mitochondrial-autophagosome synapse during mitophagy using proteomics and genetic screens.
Significance The DNA damage response (DDR) promotes survival and genome maintenance. It involves a network of kinases that phosphorylate multitude effector proteins. Although the protein involved have been studied extensively, many targets remain to be discovered. We used an unbiased approach profile DDR phosphorylation in budding yeast. reveal link between signaling metabolic pathways inositol phosphate phosphatidyl synthesis, which are required for resistance damage. Taken together, these...
RNAi screens have implicated hundreds of host proteins as HIV-1 dependency factors (HDFs). While informative, these early studies overlap poorly due to false positives and negatives. To ameliorate issues, we combined information from the existing HDF together with new performed multiple orthologous reagents (MORR). In addition being traditionally validated, MORR historical were quantitatively integrated by adaptation an established analysis program, RIGER, for collective interpretation each...
ABSTRACT Methylation of cytosine residues in DNA plays a critical role the silencing gene expression, organization chromatin structure, and cellular differentiation eukaryotes. Previous studies failed to detect 5-methylcytosine Dictyostelium genomic DNA, but recent sequencing genome revealed candidate methyltransferase ( dnmA ). The sequence also uncovered an unusual distribution potential methylation sites, CpG islands, throughout genome. DnmA belongs Dnmt2 subfamily contains all catalytic...
Differentiation is a highly regulated process whereby cells become specialized to perform specific functions and lose the ability others. In contrast, question of whether dedifferentiation genetically determined process, or merely an unregulated loss differentiated state, has not been resolved. We show here that in social amoeba Dictyostelium discoideum relies on sequence events independent original developmental state involves coordinated expression set genes. A defect one these genes,...