- RNA Research and Splicing
- RNA and protein synthesis mechanisms
- RNA Interference and Gene Delivery
- CRISPR and Genetic Engineering
- Light effects on plants
- RNA modifications and cancer
- Circadian rhythm and melatonin
- Ubiquitin and proteasome pathways
- DNA and Nucleic Acid Chemistry
- Virus-based gene therapy research
- Immune Response and Inflammation
- Bioinformatics and Genomic Networks
- Ion channel regulation and function
- Genomics and Chromatin Dynamics
- Advanced biosensing and bioanalysis techniques
- Protein Kinase Regulation and GTPase Signaling
- Monoclonal and Polyclonal Antibodies Research
- Cancer Cells and Metastasis
- interferon and immune responses
- Hippo pathway signaling and YAP/TAZ
- bioluminescence and chemiluminescence research
- Biochemical and Molecular Research
- Muscle Physiology and Disorders
- Single-cell and spatial transcriptomics
- Genetics, Aging, and Longevity in Model Organisms
Genomics Institute of the Novartis Research Foundation
2011-2021
Freedom to Live
2016
Scripps Research Institute
2003
Ionis Pharmaceuticals (United States)
1992-2003
University of California, Santa Cruz
1991
Although recent evidence has pointed to the existence of small open reading frame (smORF)-encoded microproteins in mammals, their function remains be determined. Skeletal muscle development requires fusion mononuclear progenitors form multinucleated myotubes, a critical but poorly understood process. Here we report identification Minion (microprotein inducer fusion), smORF encoding an essential skeletal specific microprotein. Myogenic lacking differentiate normally fail syncytial and...
This report describes an unbiased method for systematically determining gene function in mammalian cells. A total of 20,704 predicted human full-length cDNAs were tested induction the IL-8 promoter. number genes, including those cytokines, receptors, adapters, kinases, and transcription factors, identified that induced promoter through known regulatory sites. Proteins acted a cooperative interaction between AP-1 unrecognized cAMP response element (CRE)-like site also identified. protein,...
A human RNase III gene encodes a protein of 160 kDa with multiple domains, proline-rich, serine- and arginine-rich, an domain. The expressed purified domain cleaves double-strand RNA does not cleave single-strand RNA. is ubiquitously in tissues cell lines, the localized nucleus cell. levels transcription translation do change during different phases cycle. However, significant fraction translocated to nucleolus S phase That this involved processing pre-rRNA, but might at sites from those...
Human cells have evolved complex signaling networks to coordinate the cell cycle. A detailed understanding of global regulation this fundamental process requires comprehensive identification genes and pathways involved in various stages cell-cycle progression. To end, we report a genome-wide analysis human cycle, size, proliferation by targeting >95% protein-coding genome using small interfering RNAs (siRNAs). Analysis >2 million images, acquired quantitative fluorescence microscopy,...
Malignant melanoma is the most aggressive form of cutaneous carcinoma, accounting for 75% all deaths caused by skin cancers. Microphthalmia-associated transcription factor (MITF) a master gene regulating melanocyte development and functions as "lineage addiction" oncogene in malignant melanoma. We have identified receptor protein tyrosine kinase TYRO3 an upstream regulator MITF expression genome-wide gain-of-function cDNA screen show that induces MITF-M SOX10-dependent manner cells....
Glucocorticoids can inhibit inflammation by abrogating the activity of NF-κB, a family transcription factors that regulates production proinflammatory cytokines. To understand molecular mechanism repression NF-κB glucocorticoids, we performed high-throughput siRNA oligo screen to identify novel genes involved in this process. Here, report loss p53, tumor suppressor protein, impaired target gene glucocorticoids. Additionally, p53 also glucocorticoid receptor (GR) genes, whereas upstream and...
Large-scale functional genomics approaches are fundamental to the characterization of mammalian transcriptomes annotated by genome sequencing projects. Although current high-throughput strategies systematically survey either transcriptional or biochemical networks, analogous genome-scale investigations that analyze gene function in cells have yet be fully realized. Through transient overexpression analysis, we describe parallel interrogation ≈20,000 sequence genes cancer-related signaling...
Signal transduction pathways often use a transcriptional component to mediate adaptive cellular responses. Coactivator proteins function prominently in these as the conduit basic machinery. Here we present high-throughput cell-based screening strategy, termed “coactivator trap,” study functional interactions of coactivators with transcription factors. We applied this strategy cAMP signaling pathway, which utilizes two families coactivators, response element binding protein (CREB) (CBP)/p300...
DNA methylation is an important epigenetic modification involved in transcriptional regulation, nuclear organization, development, aging, and disease. Although methyltransferases have been characterized, the mechanisms for demethylation remain poorly understood. Using a cell-based reporter assay, we performed functional genomics screen to identify genes demethylation. Here show that RNF4 (RING finger protein 4), SUMO-dependent ubiquitin E3-ligase previously implicated maintaining genome...
Significance Although miRNAs are emerging as important regulators of diverse physiological and pathological processes, our knowledge their potential role in regulation circadian rhythms is still limited. We deployed a cell-based genome-wide screening approach successfully identified mature cell-autonomous modulators. then specifically focused on the miR-183/96/182 cluster among candidate miRNA hits revealed function both vitro vivo. This study provides resources for further understanding...
IkappaB kinase 2 (IKK2 or IKKbeta) is a component of the IKK complex that coordinates cellular response to diverse set extracellular stimuli, including cytokines, microbial infection, and stress. In an external stimulus, activated, resulting in phosphorylation subsequent proteasome-mediated degradation proteins. This event triggers nuclear import NF-kappaB transcription factor, which activates genes regulate variety fundamental biological processes, immune response, cell survival,...