A5010900307- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- CAR-T cell therapy research
- Nuclear Receptors and Signaling
- IL-33, ST2, and ILC Pathways
- Immune Response and Inflammation
- Cytokine Signaling Pathways and Interactions
- Estrogen and related hormone effects
- RNA Interference and Gene Delivery
- Chemokine receptors and signaling
- Immunotherapy and Immune Responses
- Neuropeptides and Animal Physiology
- Virus-based gene therapy research
- Macrophage Migration Inhibitory Factor
- Histone Deacetylase Inhibitors Research
- Retinoids in leukemia and cellular processes
- Peptidase Inhibition and Analysis
- Wnt/β-catenin signaling in development and cancer
- Apelin-related biomedical research
- T-cell and Retrovirus Studies
- Extracellular vesicles in disease
- Signaling Pathways in Disease
- Asthma and respiratory diseases
- Lymphoma Diagnosis and Treatment
- Viral Infectious Diseases and Gene Expression in Insects
National Cancer Institute
2015-2022
National Institutes of Health
2015-2022
Center for Cancer Research
2021-2022
Memorial Sloan Kettering Cancer Center
2007-2010
Kettering University
2010
Tufts Medical Center
2006-2009
Molecular Oncology (United States)
2006-2009
Dana-Farber Cancer Institute
2006
Harvard University
2006
Athinoula A. Martinos Center for Biomedical Imaging
2006
Abstract Nur factors are critical for proopiomelanocortin (POMC) induction by CRH in corticotrophs, but the pathways linking to unknown. In this study we show that AtT-20 corticotrophs and cAMP induce Nur77 Nurr1 expression transcription at NurRE site protein kinase A (PKA) calcium-dependent -independent mechanisms. Calcium depend on calmodulin II (CAMKII) activity, calcium-independent accounted part MAPK activation (Rap1/B-Raf/MAPK-ERK kinase/ERK1/2), demonstrated use of molecular...
Cushing syndrome is caused by an excess of adrenocorticotropic hormone (ACTH) production neuroendocrine tumors, which subsequently results in chronic glucocorticoid excess. We found that retinoic acid inhibits the transcriptional activity AP-1 and orphan receptors Nur77 Nurr1 ACTH-secreting tumor cells. Retinoic treatment resulted reduced pro-opiomelanocortin transcription ACTH production. inhibition was also observed human pituitary cells a small-cell lung cancer cell line, but not normal...
The broad complex, tramtrack, bric-a-brac-zinc finger (BTB-ZF) transcription factor promyelocytic leukemia zinc (PLZF) is required for development of the characteristic innate/effector functions NKT cells. In this study, we report characterization and functional analysis transgenic mouse T cells with forced expression PLZF. PLZF was sufficient to provide some memory/effector without need Ag stimulation or proliferation. acquisition phenotype did not require proliferation typically associated...
Expression of promyelocytic leukemia zinc finger (PLZF) protein directs the effector differentiation invariant NKT (iNKT) cells and IL-4(+) γδ cells. In this study, we show that PLZF is also required for development function IL-17(+) T We observed expressed in fetal-derived Vγ5(+) Vγ6(+) cells, which secrete IFN-γ IL-17, respectively. deficiency specifically affected leading to reduced numbers mature CD27(-)CD44(+) phenotype capable secreting IL-17. Although was not develop, when these were...
Recurrent respiratory papillomatosis (RRP) is a human papillomavirus (HPV)-driven disorder that causes substantial morbidity and can lead to fatal distal airway obstruction post-obstructive pneumonias. Patients require frequent surgical debridement of disease, no approved systemic adjuvant therapies exist.A phase II study was conducted investigate the clinical activity safety programmed death-ligand 1 (PD-L1) blockade with avelumab in patients RRP.Twelve were treated. All laryngeal RRP...
Histone deacetylase 6 (HDAC6) inhibition is associated with an increased pro-inflammatory tumor microenvironment and antitumoral immune responses. Here, we show that the HDAC6 inhibitor AVS100 (SS208) had effect in SM1 melanoma CT26 colon cancer models efficacy of anti–programmed cell death protein 1 treatment, leading to complete remission response cancer. treatment tumor-infiltrating macrophages CD8 effector T cells inflammatory gene signature. Acquired immunity long-term protection were...
MicroRNAs (miRNAs) are small, noncoding RNAs that regulate gene expression by targeting complementary sequences, referred to as miRNA recognition elements (MREs), typically located in the 3′ untranslated region of mRNAs. miR-181a is highly expressed developing thymocytes and markedly downregulated post-thymic T cells. We investigated whether endogenous can be harnessed segregate chimeric antigen receptors (CARs) TCRs between mature Lentiviral-encoded were tagged with a miR-181a–specific MRE...
NK effector cells expressing a CAR construct may be used to target T-lineage markers. In this work, we compared the activity of NK-specific CAR-NK and CAR-T framework when expressed on CD3 CD5 in T-cell malignancies. Our results show that CD3-CAR-T is more active than CD5-CAR-T eliminate malignant T vitro, however, were less efficient tumor vivo, while had antitumor diffuse xenograft model. Lack vivo efficacy correlated with downregulation levels after coculture CD3-CAR cells. The greatly...
Interleukins and their receptors are expressed intrinsically in the anterior pituitary regulate hormone production cell proliferation. It has previously been shown that interleukin-6 (IL-6) regulates secretion normal cells lines. Here we examined effects of IL-6 on propiomelanocortin (POMC) expression ACTH corticotroph adenoma vitro. We found stimulates both POMC gene cultures. This first demonstration stimulatory action human function provides further evidence for a direct cells. have...
A complete understanding of negative selection has been elusive due to the rapid apoptosis and clearance thymocytes in vivo. We report a TCR transgenic model which expression during differentiation occurs only after V(D)J-like recombination. from this transgene closely mimics endogenous TCRα locus allowing for development that is similar wild type thymocytes. This allowed us characterize phenotypic changes occurred TCR-mediated signaling self-reactive prior their deletion highly...
Thymic maturation of T cells depends on the intracellular interpretation alphabetaTCR signals by processes that are poorly understood. In this study, we report beta-catenin/Tcf signaling was activated in double-positive thymocytes response to engagement and impacted thymocyte selection. TCR combined with activation beta-catenin signaled deletion, whereas Tcf-1 deficiency rescued from negative Survival/apoptotis mediators including Bim, Bcl-2, Bcl-x(L) were alternatively influenced...
Abstract Expression of the transcription factor Zbtb1 is required for normal lymphoid development. We report in present study that maintains genome integrity immune progenitors, without which cells undergo increased DNA damage and p53-mediated apoptosis during replication differentiation. Increased Zbtb1-mutant (ScanT) progenitors was due to sensitivity stress, a consequence inefficient activation S-phase checkpoint response. affected not only but also myeloid development competitive bone...
The expression of BTB-ZF transcription factors such as ThPOK in CD4 + T cells, Bcl6 follicular helper and PLZF natural killer cells defines the fundamental nature characteristics these cells. Screening for lineage-defining genes led to discovery a subset that expressed Zbtb20. About half Zbtb20 FoxP3, factor regulatory (T regs ). were phenotypically genetically distinct from larger conventional reg population. constitutively mRNA interleukin-10 produced high levels cytokine upon primary...
Nur77 and Nurr1 are critical for proopiomelanocortin (POMC) regulation by corticotrophin releasing hormone (CRH) in corticotrophs. We analyze the activity of interleukin (IL)‐1 AtT‐20 corticotrophic cells its consequences on POMC regulation. IL‐1 induces not mRNA shows an increased transcriptional NurRE site, effect dependent p38 protein kinase activity. A mutation abrogates promoter transcription a stable clone overexpressing dominant negative form is unresponsive to IL‐1‐dependent...
Cushing syndrome is caused by an excess of adrenocorticotropic hormone (ACTH) production neuroendocrine tumors, which subsequently results in chronic glucocorticoid excess. We found that retinoic acid inhibits the transcriptional activity AP-1 and orphan receptors Nur77 Nurr1 ACTH-secreting tumor cells. Retinoic treatment resulted reduced pro-opiomelanocortin transcription ACTH production. inhibition was also observed human pituitary cells a small-cell lung cancer cell line, but not normal...
Monocytes express IL-1 and receptor antagonist (IL-1Ra) in response to lipopolysaccharide (LPS). self-induction contributes the increase following LPS stimulation. LPS-stimulated IL-1Ra production are inhibited by glucocorticoids. In present work we examined regulation of Th1 cytokine IFN-γ, Th2 IL-4, glucocorticoids human monocytes. We demonstrate that LPS-induced expression as shown blockade monocytes using a specific anti-IL-1β antibody or recombinant IL-1Ra. Glucocorticoids...
// Xianyu Zhang 1 , Ying Lu Xin Cao 2 Tao Zhen 3 and Damian Kovalovsky Experimental Immunology Branch, NCI, NIH, Maryland, USA College of Life Science Engineering, Northwest University for Nationalities, Gansu Engineering Research Center Animal Cell, Lanzhou, China Oncogenesis Development Section, National Human Genome Institute, Correspondence to: Kovalovsky, email: Keywords : Zbtb1, lymphoid, development, myeloid, differentiation, Microbiology Immune response, Immunity Received June 18,...