A5090059379- Epigenetics and DNA Methylation
- PI3K/AKT/mTOR signaling in cancer
- RNA modifications and cancer
- Virus-based gene therapy research
- T-cell and Retrovirus Studies
- Cancer-related gene regulation
- NF-κB Signaling Pathways
- RNA Research and Splicing
- Cytokine Signaling Pathways and Interactions
- RNA and protein synthesis mechanisms
- Cancer-related Molecular Pathways
- Immune Cell Function and Interaction
- Melanoma and MAPK Pathways
- Cancer, Hypoxia, and Metabolism
- interferon and immune responses
- Cancer-related molecular mechanisms research
- Protein Kinase Regulation and GTPase Signaling
- Cell death mechanisms and regulation
- Immune Response and Inflammation
- Lymphoma Diagnosis and Treatment
- T-cell and B-cell Immunology
- Animal Virus Infections Studies
- Cancer Mechanisms and Therapy
- Cancer Genomics and Diagnostics
- Herpesvirus Infections and Treatments
The Ohio State University
2019-2024
The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute
2020-2024
University School
2024
Tufts Medical Center
2012-2023
Molecular Oncology (United States)
2012-2023
Tufts University
2007-2022
Ohio University
2022
Cancer Genetics (United States)
2020-2021
Northwell Health
2021
Harvard University
2011-2017
The cancer stem cell hypothesis suggests that, unlike most cells within a tumor, resist chemotherapeutic drugs and can regenerate the various types in thereby causing relapse of disease. Thus, that selectively target offer great promise for treatment, particularly combination with chemotherapy. Here, we show low doses metformin, standard drug diabetes, inhibits cellular transformation kills four genetically different breast cancer. metformin well-defined agent, doxorubicin, both non-stem...
The v- akt oncogene codes for a 105-kilodalton fusion phosphoprotein containing Gag sequences at its amino terminus. Sequence analysis of and biochemical characterization product revealed that it protein kinase C-related serine-threonine whose cellular homolog is expressed in most tissues, with the highest amount found thymus. Although Akt kinase, part regulatory region similar to Src homology-2 domain, structural motif characteristic cytoplasmic tyrosine kinases functions protein-protein...
Hsp90 is a chaperone required for the conformational maturation of certain signaling proteins including Raf, cdk4, and steroid receptors. Natural products synthetic small molecules that bind to ATP-binding pocket in amino-terminal domain inhibit its function cause degradation these client proteins. Inhibition cells causes down-regulation an Akt kinase-dependent pathway D-cyclin expression retinoblastoma protein-dependent G1 arrest. Intracellular associated with Cdc37 complex which kinase...
Activated macrophages are described as classically activated or M1 type and alternatively M2 type, depending on their response to proinflammatory stimuli the expression of genetic markers including iNOS, arginase1, Ym1, Fizz1. Here we report that Akt kinases differentially contribute macrophage polarization, with Akt1 ablation giving rise an Akt2 resulting in phenotype. Accordingly, −/− mice were more resistant LPS-induced endotoxin shock dextran sulfate sodium (DSS)-induced colitis than...
The interleukin-2 (IL-2) receptor (IL-2R) is composed of three subunits. Of these, IL-2Ra required for high-affinity IL-2 binding, while IL-2R beta and gamma(c) are the transduction IL-2-generated signals. Signals transduced via S region (amino acids 267-322) in BAF/3 cells activate phosphatidylinositol 3-kinase (PI3-kinase) induce expression Bcl-2 c-myc. Through induction Bcl-2, inhibits apoptosis through combination c-myc it stimulates progression cell cycle. Here we show that protein...
Cyclin D expression is regulated by growth factors and necessary for the induction of mitogenesis. Herbimycin A, a drug that binds to Hsp90, induces destruction tyrosine kinases causes down-regulation cyclin an Rb-dependent arrest in G<sub>1</sub>phase cell cycle. We find D-cyclin serum its repression herbimycin A are at level mRNA translation. Induction occurs prior does not require transcription. characterized decrease synthetic rate D-cyclins changes absence half-life protein. This effect...
Cell attachment to fibronectin stimulates the integrin-dependent interaction of p85-associated phosphatidylinositol (PI) 3-kinase with focal adhesion kinase (FAK) as well activation Ras/mitogen-activated protein (MAP) pathway. However, it is not known if this PI 3-kinase-FAK increases synthesis 3-phosphorylated phosphoinositides (3-PPIs) or what role, any, played by activated in integrin signaling. We demonstrate here accumulation products, 3,4-bisphosphate [PI(3,4)P2] and PI(3,4,5)P3, AKT...
The avian sarcoma virus 16 (ASV 16) is a retrovirus that induces hemangiosarcomas in chickens. Analysis of the ASV genome revealed it encodes an oncogene derived from cellular gene for catalytic subunit phosphoinositide 3-kinase (PI 3-kinase). referred to as v- p3k , and like its counterpart c- potent transforming cultured chicken embryo fibroblasts (CEFs). products viral genes have PI activity. CEFs transformed with either showed elevated levels phosphatidylinositol 3,4-bisphosphate...
The Gfi-1 proto-oncogene encodes a zinc finger protein with six C2H2-type, C-terminal motifs and is activated by provirus integration in T-cell lymphoma lines selected for interleukin-2 independence culture primary retrovirus-induced thymomas. expression adult animals restricted to the thymus, spleen, testis enhanced mitogen-stimulated splenocytes. In this report, we show that 55-kDa nuclear binds DNA sequence-specific manner. binding site, TAAATCAC(A/T)GCA, was defined via random...
The TCL1 oncogene at 14q32.1 is involved in the development of human mature T-cell leukemia. mechanism action Tcl1 unknown. Because virus containing v-akt causes lymphoma mice and Akt a key player transduction antiapoptotic proliferative signals T-cells, we investigated whether function same pathway. Coimmunoprecipitation experiments showed that endogenous Akt1 physically interact leukemia cell line SupT11; both proteins also when cotransfected into 293 cells. Using several AKT1 constructs...
The serine-threonine kinase Akt is a downstream target of phosphoinositide 3-kinase (PI 3-kinase); it activated by the 3-phosphate-dependent kinases PDK1 and PDK2. Certain mutated forms induce oncogenic transformation in chicken embryo fibroblast cultures hemangiosarcomas young chickens. This ability to transform cells depends on localization at plasma membrane activity Akt. A transdominant negative form interferes with induced p3k oncogene, which codes for an PI 3-kinase. therefore...
The Akt protooncogene encodes a serine-threonine protein kinase which is activated by growth factor-generated signals that are transduced via the phosphatidylinositol 3′-kinase (PI3-K). Earlier studies suggested activation of PI3-K may be mediated binding D3-phosphorylated phosphoinositides to pleckstrin homology (PH) domain. On basis these studies, it was hypothesized direct target. To test this hypothesis, we reconstituted pathway in baculovirus-infected Sf9 cells. results showed Akt,...
The Gfi-1 proto-oncogene is activated by provirus insertion in T-cell lymphoma lines selected for interleukin-2 (IL-2) independence culture and primary retrovirus-induced thymomas encodes a nuclear, sequence-specific DNA-binding protein. Here we show that position- orientation-independent active transcriptional repressor, whose activity depends on 20-amino-acid N-terminal repressor domain, coincident with nuclear localization motif. sequence of the domain related to Gfi-1B, Gfi-1-related...