A5103209255- T-cell and B-cell Immunology
- NF-κB Signaling Pathways
- Monoclonal and Polyclonal Antibodies Research
- Acute Myeloid Leukemia Research
- Glycosylation and Glycoproteins Research
- Immune Cell Function and Interaction
- Chronic Lymphocytic Leukemia Research
- Histone Deacetylase Inhibitors Research
- Cytokine Signaling Pathways and Interactions
- Bone Metabolism and Diseases
- Viral Infections and Vectors
- Hematopoietic Stem Cell Transplantation
- Neurotransmitter Receptor Influence on Behavior
- Acute Lymphoblastic Leukemia research
- Neuroscience and Neuropharmacology Research
- Corneal Surgery and Treatments
- Bone health and treatments
- Traditional Chinese Medicine Studies
- Mesenchymal stem cell research
- Fibroblast Growth Factor Research
- Traditional Chinese Medicine Analysis
- Immune Response and Inflammation
- Atherosclerosis and Cardiovascular Diseases
- FOXO transcription factor regulation
- Protein Degradation and Inhibitors
Case Western Reserve University
2020-2024
Cornell University
2021
Louis Stokes Cleveland VA Medical Center
2020-2021
University of Iowa
2015-2020
University of Rochester Medical Center
2011-2019
Emory University Hospital
2013
Qinhuangdao Glass Industry Research and Design Institute (China)
2009
Duke Medical Center
2006-2008
Juntendo University
2000-2007
Duke University Hospital
2006
CD20 monoclonal antibody (mAb) immunotherapy is effective for lymphoma and autoimmune disease. In a mouse model of using anti–mouse mAbs, the innate monocyte network depletes B cells through immunoglobulin (Ig)G Fc receptor (FcγR)-dependent pathways with hierarchy IgG2a/c>IgG1/IgG2b>IgG3. To understand molecular basis these mAb subclass differences, cell depletion was assessed in mice deficient or blocked stimulatory FcγRI, FcγRIII, FcγRIV, FcR common γ chain, inhibitory...
The cytokines RANKL and TNF activate NF-κB signaling in osteoclast precursors (OCPs) to induce (OC) formation. Conversely, can limit OC formation through p100, which acts as an inhibitor, receptor–associated receptor 3 (TRAF3); however, a role for TRAF3 RANKL-mediated is unknown. We found that limits RANKL-induced osteoclastogenesis by suppressing canonical noncanonical signaling. Conditional OC-specific Traf3-KO (cKO) mice had mild osteoporosis increased induced degradation via the...
Serotonin [5-hydroxytryptamine (5-HT)] is a major therapeutic target of psychiatric disorders. Tryptophan hydroxylase (TPH) catalyzes the rate-limiting reaction in biosynthesis 5-HT. Two isoforms (TPH1 and TPH2) having tryptophan hydroxylating activity were identified. Association studies have revealed possible TPH1 involvement conditions behavioral traits. However, mRNA was reported to be mainly expressed pineal gland periphery barely detected brain. Therefore, contribution brain 5-HT...
Abstract Inflammaging induces osteoporosis by promoting bone destruction and inhibiting formation. TRAF3 limits RANKL-induced NF-κB signaling in osteoclast precursors. However, the role of mesenchymal progenitor cells (MPCs) is unknown. Mice with deleted MPCs develop early onset due to reduced formation enhanced destruction. In young mice prevents β-catenin degradation maintains osteoblast protein levels decrease murine human samples during aging when TGFβ1 released from resorbing bone....
Abstract FcγRIIB1 molecules serve as negative feedback regulator for B cell Ag receptor-elicited activation of cells; thus, any impaired function may possibly be related to aberrant activation. We earlier found deletion polymorphism in the Fcgr2b promoter region among mouse strains which systemic autoimmune disease-prone NZB, BXSB, MRL, and diabetes-prone nonobese diabetic, but not NZW, BALB/c, C57BL/6 mice have two identical sites, consisting 13 3 nucleotides. In this study, we established...
RelB and nuclear factor κB (NF-κB2) are the main effectors of NF-κB noncanonical signaling play critical roles in many physiological processes. However, their role hematopoietic stem/progenitor cell (HSPC) maintenance has not been characterized. To investigate this, we generated RelB/NF-κB2 double-knockout (dKO) mice found that dKO HSPCs have profoundly impaired engraftment self-renewal activity after transplantation into wild-type recipients. Transplantation bone marrow cells to assess...
Abstract Acute myeloid leukemia (AML) is maintained by self-renewing leukemic stem cells (LSCs). A fundamental problem in treating AML that conventional therapy fails to eliminate LSCs, which can reinitiate leukemia. Heat shock transcription factor 1 (HSF1), a central regulator of the stress response, has emerged as an important target cancer therapy. Using genetic Hsf1 deletion and direct HSF1 small molecule inhibitor, we show specifically required for maintenance AML, while sparing...
Canonical NF-κB signaling is constitutively activated in acute myeloid leukemia (AML) stem cells and required for maintenance of the self-renewal (LSCs). However, any potential role non-canonical AML has been largely overlooked. Here, we report that stabilization NF-κB-inducing kinase (NIK) suppresses AML. Mechanistically, NIK activates represses canonical signaling. In addition, NIK-induced activation upregulates Dnmt3a downregulates Mef2c, which promotes development, respectively....
The immune and nervous systems display considerable overlap in their molecular repertoire. Molecules originally shown to be critical for responses also serve neuronal functions that include normal brain development, differentiation, synaptic plasticity, behavior. We show here FcgammaRIIB, a low-affinity immunoglobulin G Fc receptor, CD3 are involved cerebellar functions. Although membranous FcgammaRIIB crucial regulators on different cells the system, both CD3epsilon expressed Purkinje...
Abstract IL‐5 preferentially activates B1 cells to produce natural antibodies cross‐reactive self antigens. To determine the role of in antibody‐mediated autoimmune disease, we generated systemic lupus erythematosus (SLE)‐prone (NZB×NZW)F1 mice congenic for transgene (TG‐F1). The unexpectedly reduced incidence nephritis. Anti‐DNA sera and those produced by splenic B vitro were markedly decreased TG‐F1 mice, while total polyclonal Ig levels comparable transgene‐negative (non‐TG‐F1)...
Abstract Immune complex (IC)-mediated tissue inflammation is controlled by stimulatory and inhibitory IgG Fc receptors (FcγRs). Systemic lupus erythematosus a prototype of IC-mediated autoimmune disease; thus, imbalance these two types FcγRs probably involved in pathogenesis. However, how to what extent each FcγR contributes the disease remains unclear. In lupus-prone BXSB mice, while are intact, FcγRIIB expression impaired because promoter region polymorphism. To dissect roles FcγRs, we...
Previously we have shown that loss of non-canonical NF-κB signaling impairs self-renewal hematopoietic stem/progenitor cells (HSPCs). This prompted us to investigate whether persistent activation the will supportive effects on HSPC self-renewal. NF-κB-inducing kinase (NIK) is an important mainly activates pathway through directly phosphorylating IKKα. In contrast our expectations, constitutive NIK in system leads bone marrow (BM) failure and postnatal lethality due intrinsic impairment...
Philadelphia chromosome-positive (Ph+) T-cell acute lymphoblastic leukemia (T-ALL) is a rare and aggressive type of leukemia. The chromosome the hallmark chronic myeloid (CML). differentiation between Ph+ T-ALL crisis CML may be problematic in some cases. Here, we report case de novo that presented diagnostic challenge. overall clinical, immunophenotypic, cytogenetic, xenotransplantation results suggest diagnosis T-ALL. patient was treated with induction chemotherapy including imatinib...
Systemic lupus erythematosus (SLE), a complex multigenic disease, is characterized by hypergammaglobulinemia, autoantibody production and immune complex-type nephritis. In addition to these signs symptoms in SLE, there can be of neurological disorders, including anxiety. To clarify mechanisms governing the anxiety seen lupus, we carried out genome-wide scans, found that region interferon-alpha (IFN-alpha) on NZB chromosome 4 significantly linked anxiety-like behavior SLE-prone New Zealand...
TRAF-interacting protein with forkhead-associated domain B (TIFAB), an inhibitor of NF-kB signaling, plays critical roles in hematopoiesis, myelodysplastic neoplasms, and leukemia. We previously demonstrated that Tifab enhances KMT2A::MLLT3-driven acute myeloid leukemia (AML) by either upregulating Hoxa9 or through ubiquitin-specific peptidase 15 (USP15)-mediated downregulation p53 signaling. In this study, we show deletion KMT2A::MLLT3-induced AML impairs stem/progenitor cell (LSPC)...
Key Points Common progenitor cells exist in clonally related concomitant chronic lymphocytic leukemia and acute myeloid leukemias. CLL dedifferentiated to posttransplantation.