A5025428025- Prostate Cancer Treatment and Research
- T-cell and B-cell Immunology
- DNA Repair Mechanisms
- Immune Cell Function and Interaction
- Immunotherapy and Immune Responses
- MicroRNA in disease regulation
- Prostate Cancer Diagnosis and Treatment
- Cancer, Lipids, and Metabolism
- Estrogen and related hormone effects
- Cytomegalovirus and herpesvirus research
- CRISPR and Genetic Engineering
- Telomeres, Telomerase, and Senescence
- interferon and immune responses
- Glutathione Transferases and Polymorphisms
- Genomics and Chromatin Dynamics
- Biopolymer Synthesis and Applications
- RNA Interference and Gene Delivery
- Chemical Reactions and Isotopes
- Circular RNAs in diseases
- NF-κB Signaling Pathways
- PARP inhibition in cancer therapy
- CAR-T cell therapy research
- Genetics, Aging, and Longevity in Model Organisms
- Cytokine Signaling Pathways and Interactions
- Cancer therapeutics and mechanisms
Memorial Sloan Kettering Cancer Center
2014-2023
Cornell University
1965-2022
National Taiwan University
2015
Hearst (United States)
2009-2011
Kettering University
1965
Generation of cellular heterogeneity is an essential feature the adaptive immune system. This best exemplified during humoral response when expanding B cell clone assumes multiple fates, including class-switched cells, antibody-secreting plasma and memory cells. Although each type for immunity, their generation must be exquisitely controlled because a cannot revert back to parent isotype, terminally differentiated contribute pool. In this study, we show that environmental sensor, aryl...
Significance The tumor suppressors BRCA1 and ATM have both been implicated in the early steps of homologous recombination, also termed homology-directed repair (HDR). However, how genetically interacts with this process is unclear. In mice carrying a breast cancer-derived mutation C-terminal (BRCT) domain, we find that becomes essential for supporting residual levels HDR necessary to DNA break. ATM-mediated not affected by status 53BP1, an antagonizing factor BRCA1. loss associated synthetic...
Rap1 (repressor activator protein 1) is a conserved multifunctional initially identified as transcriptional regulator of ribosomal genes in Saccharomyces cerevisiae but subsequently shown to play diverse functions at multiple chromosomal loci, including telomeres. The function appears be evolutionarily plastic, especially the budding yeast lineages. We report here our biochemical and molecular genetic characterizations Candida albicans Rap1, which exhibits an unusual, miniaturized domain...
Abstract MicroRNA (miR)-mediated regulation of protein abundance is a pervasive mechanism directing cellular processes. The well-studied and abundant miR-182 has previously been implicated in many aspects T cell function, DNA repair, cancer. In this study, we show that the most highly induced miR B cells undergoing class-switch recombination. To elucidate requirement lymphocyte extensively characterized mice with targeted deletion Mir182. We despite its dramatic induction, loss minimal...
The yeast telomerase regulatory protein Est3 is required for telomere maintenance in vivo, and shares intriguing structural functional similarities with the mammalian telomeric TPP1. Here we report our physical characterizations of homologues from Candida parapsilosis Lodderomyces elongisporus , which bear unique N- C-terminal tails addition to a conserved central OB fold. We show that these form stable complexes TEN domain reverse transcriptase. Efficient complex formation requires both...
The immunoglobulin heavy chain (Igh) locus features a dynamic chromatin landscape to promote class switch recombination (CSR), yet the mechanisms that regulate this remain poorly understood. CHD4, component of remodeling NuRD complex, directly binds H3K9me3, an epigenetic mark present at Igh during CSR. We find CHD4 is essential for early B cell development but dispensable homeostatic maintenance mature, naive cells. However, loss in mature cells impairs CSR because suboptimal targeting AID...
C-Maf plays an important role in regulating cytokine production TH cells. Its transactivation of IL-4 is optimized by phosphorylation at Tyr21, Tyr92, and Tyr131. However, the molecular mechanism its tyrosine remains unknown. In this study, we demonstrate that Tec kinase family member Tec, but not Rlk or Itk, a c-Maf enhances c-Maf-dependent promoter activity. This effect counteracted Ptpn22, which physically interacts with facilitates dephosphorylation thereby attenuating transcriptional We...
Abstract Although primary humoral responses are vital to durable immunity, fine-tuning is critical preventing catastrophes such as autoimmunity, chronic inflammation, and lymphomagenesis. MicroRNA (miRNA)-mediated regulation particularly well suited for roles in physiology. Expression of clustered paralogous miR-182, miR-96, miR-183 (collectively, 183c) robustly induced upon B cell activation, entry into the germinal center, plasmablast differentiation. 183cGT/GT mice lacking 183c miRNA...
The DNA damage response protein ATM has long been known to influence class switch recombination in ex vivo-cultured B cells. However, an assessment of cell-intrinsic requirement humoral responses vivo was confounded by the fact that its germline deletion affects T cell function, and B:T interactions are critical for immune responses. In this study, we demonstrate cell-specific mice leads reduction germinal center (GC) frequency size immunization. We find loss induces apoptosis GC cells,...
DNA double-strand breaks (DSBs) serve as obligatory intermediates for Ig heavy chain (Igh) class switch recombination (CSR). The mechanisms by which DSBs are resolved to promote long-range end-joining while suppressing genomic instability inherently associated with yet be fully elucidated. Here, we use a targeted short-hairpin RNA screen in B-cell lymphoma line identify the BRCT-domain protein BRIT1 an effector of CSR. We show that conditional genetic deletion mice leads marked increase...
During the development of humoral immunity, activated B lymphocytes undergo vigorous proliferative, transcriptional, metabolic, and DNA remodeling activities; hence, their genomes are constantly exposed to an onslaught genotoxic agents processes. Branched intermediates generated during replication recombinational repair pose genomic threats if left unresolved so, they must be eliminated by structure-selective endonucleases preserve integrity these transactions for faithful duplication...
<p>Supplementary Figure S1 - PDF file 1194K, Gamma-H2AX foci and Comet assay normalized of LNCaP plus or minus androgen to time 0</p>
<p>Supplementary Figure S2 - PDF file 1705K, LNCaP cell cycle distribution by PI and BrdU analyses plus or minus androgen</p>
<p>Supplementary Figure S4 - PDF file 793K, Immunoblot of LNCaP demonstrating LIG4 knockdown</p>
<p>Supplementary Figure S3 - PDF file 1337K, LNCaP cell cycle distribution by PI and BrdU analyses plus or minus ARN-509</p>
<p>Supplementary Figure S4 - PDF file 793K, Immunoblot of LNCaP demonstrating LIG4 knockdown</p>