A5083504150- DNA Repair Mechanisms
- Ubiquitin and proteasome pathways
- Cancer-related Molecular Pathways
- Cancer Research and Treatments
- Herpesvirus Infections and Treatments
- CRISPR and Genetic Engineering
- Polyomavirus and related diseases
- Acute Myeloid Leukemia Research
- Cancer-related molecular mechanisms research
- interferon and immune responses
- Advanced biosensing and bioanalysis techniques
- Genomics and Chromatin Dynamics
- Cell death mechanisms and regulation
- HIV/AIDS drug development and treatment
- Immune Response and Inflammation
- NF-κB Signaling Pathways
- Virus-based gene therapy research
- Cytomegalovirus and herpesvirus research
- RNA Interference and Gene Delivery
University of California, San Diego
2009-2012
Salk Institute for Biological Studies
2009-2012
Genentech
2012
Institute for Advanced Study
2004
Rockefeller University
2004
Memorial Sloan Kettering Cancer Center
2004
Albert Einstein College of Medicine
2004
De-ubiquitinating enzyme BAP1 is mutated in a hereditary cancer syndrome with increased risk of mesothelioma and uveal melanoma. Somatic mutations occur various malignancies. We show that mouse Bap1 gene deletion lethal during embryogenesis, but systemic or hematopoietic-restricted adults recapitulates features human myelodysplastic (MDS). Knockin mice expressing 3xFlag tag revealed interacts host cell factor-1 (HCF-1), O-linked N-acetylglucosamine transferase (OGT), the polycomb group...
Cellular restriction factors responding to herpesvirus infection include the ND10 components PML, Sp100 and hDaxx. During initial stages of HSV-1 infection, novel sub-nuclear structures containing these proteins form in association with incoming viral genomes. We report that several cellular DNA damage response also relocate sites associated genomes where they contribute front line defense. show recruitment repair is independent components, instead coordinated by ubiquitin ligases RNF8...
Malignancies arising from mutation of tumor suppressors have unexplained tissue proclivity. For example, BAP1 encodes a widely expressed deubiquitinase for histone H2A, but germline mutations are predominantly associated with uveal melanomas and mesotheliomas. We show that inactivation causes apoptosis in mouse embryonic stem cells, fibroblasts, liver, pancreatic not melanocytes mesothelial cells. Ubiquitin ligase RNF2, which silences genes by monoubiquitinating promoted BAP1-deficient cells...
Mucosa-associated lymphoid tissue (MALT) lymphoma is the most common extranodal cell neoplasia; it frequently follows chronic bacteria-induced inflammation in various tissues. MALT lymphomas are characterized genetically by t(11;18)(q21;q21) translocation, which yields chimeric transcripts encoding structurally distinct API2/MALT1 fusion proteins. In this study, we provide functional evidence for contribution of proteins to transformation cells culture activating NF-κB pathway through a...
The deubiquitinating enzyme BAP1 is mutated in a hereditary cancer syndrome with high risk of mesothelioma and melanocytic tumors. Here, we show that Bap1 deletion melanocytes cooperates the constitutively active, oncogenic form BRAF (BRAFV600E ) UV to cause melanoma mice, albeit at very low frequency. In addition, Bap1-null cells derived from mouse tumors are more aggressive colonize grow distant sites than their wild-type counterparts. Molecularly, cell lines have increased DNA damage...