A5091434372- T-cell and Retrovirus Studies
- Animal Disease Management and Epidemiology
- Vector-Borne Animal Diseases
- Cancer-related gene regulation
- Virus-based gene therapy research
- Viral Infections and Immunology Research
- Protein Degradation and Inhibitors
- Signaling Pathways in Disease
- Animal Virus Infections Studies
- HIV Research and Treatment
- Viral-associated cancers and disorders
- Galectins and Cancer Biology
- CRISPR and Genetic Engineering
- Immune Cell Function and Interaction
- HIV/AIDS drug development and treatment
- Zoonotic diseases and public health
- Lymphoma Diagnosis and Treatment
- Acute Lymphoblastic Leukemia research
- Cytomegalovirus and herpesvirus research
- Vascular Tumors and Angiosarcomas
- Infectious Diseases and Mycology
- Hemophilia Treatment and Research
- Retinoids in leukemia and cellular processes
- Veterinary Practice and Education Studies
- CAR-T cell therapy research
The Ohio State University
2015-2024
The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute
2009-2023
Ohio University
2017
Medical Genetics Center
2008
Eastern Virginia Medical School
2005
Comprehensive Blood & Cancer Center
2001-2004
U-M Rogel Cancer Center
2003-2004
Kyushu University
2001
Cancer Hospital and Research Institute
2000
Vanderbilt University
1994-1998
Human T-cell leukemia virus type 1 (HTLV-1) is the causal agent of a neoplastic disease CD4+ T cells, adult (ATL), and inflammatory diseases including HTLV-1 associated myelopathy/tropical spastic paraparesis, dermatitis, lung diseases. ATL which constitutively express CD25, resemble CD25+CD4+ regulatory cells (T(reg)). Approximately 60% cases indeed harbor leukemic that FoxP3, key transcription factor for T(reg) cells. encodes an antisense transcript, bZIP (HBZ), expressed in all cases. In...
The selection of chromosomal targets for retroviral integration varies markedly, tracking with the genus retrovirus, suggestive targeting by binding to cellular factors. γ-Retroviral murine leukemia virus (MLV) DNA into host genome is favored at transcription start sites, but underlying mechanism this preference unknown. Here, we have identified bromodomain and extraterminal domain (BET) proteins (Brd2, -3, -4) as cellular-binding partners MLV integrase. We show that purified recombinant...
Human T lymphotropic viruses (HTLVs) are complex deltaretroviruses that do not contain a proto-oncogene in their genome, yet capable of transforming primary lymphocytes both vitro and vivo. There four known strains HTLV including type 1 (HTLV-1), HTLV-2, HTLV-3 HTLV-4. HTLV-1 is primarily associated with adult cell leukemia (ATL) HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). HTLV-2 rarely pathogenic sporadically neurological disorders. have been no diseases or HTLV-4...
In resting T lymphocytes, the transcription factor NF-kappaB is sequestered in cytoplasm via interactions with members of I kappa B family inhibitors, including IkappaBalpha and IkappaBbeta. During normal T-cell activation, rapidly phosphorylated, ubiquitinated, degraded by 26S proteasome, thus permitting release functional NF-kappaB. contrast to its transient pattern nuclear induction during an immune response, constitutively activated cells expressing Tax transforming protein human...
Human retroviruses are derived from simian ones through cross-species transmission. These associated with little pathogenicity in their natural hosts, but humans, HIV causes AIDS, and human T-cell leukemia virus type 1 (HTLV-1) induces adult leukemia-lymphoma (ATL). We analyzed the proviral sequences of HTLV-1, HTLV-2, (STLV-1) Japanese macaques (
ABSTRACT Human T-lymphotropic virus type 1 (HTLV-1) causes adult T-cell leukemia/lymphoma and is associated with a variety of immune-mediated disorders. The role four open reading frames (ORFs), located between env the 3′ long terminal repeat HTLV-1, in mediating disease not entirely clear. By differential splicing, ORF II encodes two proteins, p13 p30 , both which have been functionally defined. localizes to mitochondria may alter configuration tubular network this cellular organelle....
Abstract In the autoimmune disease multiple sclerosis and its animal model, experimental encephalomyelitis (EAE), expansion of pathogenic, myelin-specific Th1 cell populations drives active disease; selectively targeting this process may be basis for a new therapeutic approach. Previous studies have hinted at role protein arginine methylation in immune responses, including T cell–mediated autoimmunity EAE. However, conclusive methyltransferase (PRMT) enzymes that catalyze these reactions has...
Adult T-cell leukemia/lymphoma (ATLL) is an aggressive malignancy with a poor prognosis current therapy. Here we report genome-wide CRISPR-Cas9 screening of ATLL models, which identified CDK6, CCND2, BATF3, JUNB, STAT3, and IL10RB as genes that are essential for the proliferation and/or survival cells. As single agent, CDK6 inhibitor palbociclib induced cell cycle arrest apoptosis in models wild-type TP53. had inactivated TP53 genetically were relatively resistant to owing compensatory CDK2...
Human T-cell leukemia virus type 1 (HTLV-1) is a retrovirus responsible for adult leukemia/lymphoma, severe and fatal CD4+ malignancy. Additionally, HTLV-1 can lead to chronic progressive neurodegenerative disease known as HTLV-1-associated myelopathy/tropical spastic paraparesis. Unfortunately, the prognosis HTLV-1-related diseases generally poor, effective treatment options are limited. In this study, we designed synthesized codon optimized envelope (Env) mRNA encapsulated in lipid...
ABSTRACT Human T-lymphotropic virus type 1 (HTLV-1) is a complex retrovirus encoding regulatory and accessory genes in four open reading frames (ORF I to IV) of the pX region. Emerging evidence indicates an important role for ORF I-encoded protein p12 viral replication, but its contribution pathogenesis remains be defined. conserved, membrane-associated containing SH3-binding motifs (PXXP). Its interaction with interleukin-2 (IL-2) receptor β- γ-chains implies involvement intracellular...
ABSTRACT Human T-cell leukemia virus type 1 (HTLV-1) and HTLV-2 are complex retroviruses that persist in the host, eventually causing neurological disease a small percentage of infected individuals. In addition to structural enzymatic proteins, HTLV encodes regulatory (Tax Rex) accessory (open reading frame I II) proteins. The viral Tax Rex proteins positively regulate production. activates cellular transcription promote growth and, ultimately, malignant transformation. acts...
Human T-cell leukemia virus type 1 (HTLV-1) infection causes adult and is associated with a variety of lymphocyte-mediated disorders. It has been hypothesized that highly regulated pattern HTLV-1 gene expression critical for survival disease pathogenesis. In this study, real-time reverse transcriptase PCR was used to determine the kinetics viral in cells transiently transfected an proviral plasmid, newly infected human peripheral blood mononuclear (PBMCs), PBMCs from rabbits. The profiles...
ABSTRACT Human T lymphotropic virus type 1 (HTLV-1) and HTLV-2 are related but pathogenically distinct viruses. HTLV-1 mainly causes adult cell leukemia, while is not associated with leukemia. In vitro , predominantly transform CD4 + CD8 cells, respectively: the genetic determinant maps to viral envelope. Herein, we investigate whether this transformation tropism occurs during initial infection or subsequently cellular process. Since most individuals chronically infected at time of...
The PXIXIT calcineurin binding motif or highly related sequences are found in a variety of calcineurin-binding proteins yeast, mammalian cells, and viruses. accessory protein p12I encoded the HTLV-1 pX ORF I promotes T cell activation during early stages infection by activating nuclear factor activated cells (NFAT) through calcium release from endoplasmic reticulum. We identified p12I, conserved motif, which is homologous with NFAT. Both immunoprecipitation calmodulin agarose bead pull-down...