- T-cell and B-cell Immunology
- NF-κB Signaling Pathways
- Immune Cell Function and Interaction
- RNA Research and Splicing
- Nuclear Structure and Function
- Immune Response and Inflammation
- RNA and protein synthesis mechanisms
- Circadian rhythm and melatonin
- Cytokine Signaling Pathways and Interactions
- Cell Adhesion Molecules Research
- Pancreatic function and diabetes
- Light effects on plants
- Neurobiology and Insect Physiology Research
- CAR-T cell therapy research
- Cell death mechanisms and regulation
- RNA modifications and cancer
- Sleep and Wakefulness Research
- Psychological and Temporal Perspectives Research
- Epigenetics and DNA Methylation
- Immunotherapy and Immune Responses
California Institute of Technology
2021-2022
Rockefeller University
2003-2019
Max Delbrück Center
2001
INTRODUCTION The subcellular compartmentalization of eukaryotic cells requires selective transport folded proteins and protein-nucleic acid complexes. Embedded in nuclear envelope pores, which are generated by the circumscribed fusion inner outer membranes, pore complexes (NPCs) sole bidirectional gateways for nucleocytoplasmic transport. ~110-MDa human NPC is an ~1000-protein assembly that comprises multiple copies ~34 different proteins, collectively termed nucleoporins. symmetric core...
B cell life depends critically on the cytokine cell–activating factor of tumor necrosis family (BAFF). Lack BAFF signaling leads to death and immunodeficiency. Excessive promotes lupus-like autoimmunity. Despite great importance biology, its mechanism is not well characterized. We show that initiates transcriptional programs, which support survival, metabolic fitness, readiness for antigen-induced proliferation. further identify a BAFF-specific protein kinase C β–Akt axis, provides...
B cell activating factor (BAFF) signals through BAFF-R to promote mature survival. Recent analyses of BAFF-induced signaling revealed direct association between augmented metabolic fitness and activation Akt, one the key regulators The strongest most reproducible induction Akt occurs with significant delay (24 h) after BAFF treatment, where it precedes anabolism. It was also recently shown that induces sustained Erk increased turnover proapoptotic molecule Bim. Here we show these pathways...
Antigen receptor signaling is known to activate NF-κB in lymphocytes. While T-cell-receptor-induced activation critically depends on novel protein kinase C θ (PKCθ), the role of PKCs B-cell stimulation has not been elucidated. In primary murine splenic B cells, we found high expression δ and ɛ but only weak isoform. Rottlerin blocks phorbol ester (phorbol myristate acetate [PMA])- or (BCR)-mediated c-Jun N-terminal (JNK) T cells a similar extent, suggesting that are positive regulators...
The NuRD complex contains both chromatin remodeling and histone deacetylase activities. Mice lacking the MTA2 subunit of show developmental defects in pro-B, pre-B, immature B, marginal zone B cells, abnormal germinal center cell differentiation during immune responses. Mta2 inactivation also causes a derepression Igll1 VpreB1 genes pre-B cells. Furthermore, MTA2/NuRD interacts directly with AIOLOS/IKAROS shows striking overlap target human suggesting functional inter-dependence between...
Abstract The nuclear pore complex (NPC) is the sole bidirectional gateway for nucleocytoplasmic transport. Despite recent progress in elucidating NPC symmetric core architecture, asymmetrically decorated cytoplasmic face, essential mRNA export and a hotspot nucleoporin-associated diseases, has remained elusive. Here, we report composite structure of entire human face obtained by combining biochemical reconstitution, crystal determination, docking into cryo-electron tomographic...