A5040094455- Cytokine Signaling Pathways and Interactions
- IL-33, ST2, and ILC Pathways
- Cancer-related Molecular Pathways
- PI3K/AKT/mTOR signaling in cancer
- Biochemical and Molecular Research
- Immune Cell Function and Interaction
- Microscopic Colitis
- Lung Cancer Treatments and Mutations
- Hematopoietic Stem Cell Transplantation
- Ubiquitin and proteasome pathways
- RNA modifications and cancer
- Cancer Mechanisms and Therapy
- Cytomegalovirus and herpesvirus research
- Viral-associated cancers and disorders
- Genomics and Chromatin Dynamics
- Immunotherapy and Immune Responses
- Pediatric health and respiratory diseases
- Protein Tyrosine Phosphatases
- Lymphoma Diagnosis and Treatment
- Systemic Lupus Erythematosus Research
- Histiocytic Disorders and Treatments
- T-cell and Retrovirus Studies
- CAR-T cell therapy research
- Tuberculosis Research and Epidemiology
- Cancer-related gene regulation
New York University
2015-2022
NYU Langone’s Laura and Isaac Perlmutter Cancer Center
2021
Indiana University School of Medicine
2021
Institute of Oncology Research
2012-2017
Università della Svizzera italiana
2017
Molecular Oncology (United States)
2017
Significance The transcription factor STAT3 is involved in multiple oncogenic signaling pathways and an attractive therapeutic target. This study shows that a potent inhibitor of interferes with mitochondrial activity protein homeostasis, leading to synthetic lethality effect glucose-depleted cancer cells. These findings provide rationale for novel strategies based on the use inhibitors treatment.
STAT3 is a key element in many oncogenic pathways and, like other transcription factors, an attractive target for development of novel anticancer drugs. However, interfering with functions has been difficult task and very few small molecule inhibitors have made their way to the clinic. OPB‐31121, compound currently clinical trials, reported affect signaling, although its mechanism action not unequivocally demonstrated. In this study, we used combined computational experimental approach...
Deregulated activity of transcription factors (TFs) the Sp/KLF family, like Sp1, Sp3 and Sp4, consequent over-expression Sp-regulated genes occur frequently in human cancers. This provides rationale for development inhibitors Sp TFs as cancer therapeutics. Mithramycin A (MTM-A) is a natural polyketide that binds GC-rich DNA sequences, inhibits exhibits potent antitumor experimental systems. However, clinical use MTM-A limited by severe toxicity compound. Here, we studied two analogues, which...
Enhancement of cellular senescence in tumours triggers a stable cell growth arrest and activation an antitumour immune response that can be exploited for cancer therapy. Currently, there are only limited number targeted therapies act by increasing cancers, but the majority them not selective also target healthy cells. Here we developed chemogenomic screening to identify compounds enhance PTEN-deficient cells without affecting normal By using this approach, identified casein kinase 2 (CK2) as...
Maintenance of immune homeostasis involves a synergistic relationship between the host and microbiome. Canonical interferon (IFN) signaling controls responses to acute microbial infection, through engagement STAT1 transcription factor. However, contribution tonic levels IFN in absence infection remains largely unexplored. We report that KO mice spontaneously developed an inflammatory disease marked by myeloid hyperplasia splenic accumulation hematopoietic stem cells. Moreover, these animals...
STAT3 is a transcription factor involved in several cellular activities including inflammation, proliferation, and survival, but it also plays non-transcriptional role modulating mitochondrial metabolism. Given its diverse functions human cancers, an emerging therapeutic target. Here we show that OPB-51602, small molecule inhibitor of STAT3, highly toxic STAT3-dependent manner. Specifically, drug toxicity depends on as tumor cells expressing only mitochondrially restricted form are sensitive...
Signal transducer and activator of transcription 3 (STAT3) is a factor with roles in inflammation tumorigenicity. A fraction STAT3 localizes mitochondria, where it augments tumorigenesis via regulation mitochondrial functions, including modulation respiration redox status. We show novel mechanism for homeostasis triple-negative breast cancer cells. Loss diminished complex I dehydrogenase activity impaired NAD+ regeneration, leading to expression glutathione biosynthetic genes other...
Abstract The transcription factor (TF) STAT3 is an attractive target for development of anticancer drugs. over-expressed and activated in many human malignancies has important role multiple oncogenic signaling pathways affecting proliferation, survival metabolic adaptation cancer cells. It been difficult, however, to develop effective inhibitors STAT3. In this study, we performed in-depth analysis the mechanism action two compounds, OPB-31121 OPB-51602, which are currently undergoing...
Abstract Transcription factors (TFs) represent attractive targets for cancer therapy. However, very few direct TF inhibitors are currently in the clinic. STAT3 is overexpressed and activated many human cancers promoting proliferation, survival metabolic adaptation of cells. In this study we investigated mechanism action two new anticancer compounds, OPB-31121 OPB-51602, evaluated phase I clinical trials. Computational docking molecular dynamic simulation (MDS) showed that compounds bound to...
STAT3 is a transcription factor involved in numerous cellular activities, including inflammation, proliferation, and survival, but it also plays non-transcriptional role modulating mitochondrial metabolism. Given its diverse functions human cancer, an emerging therapeutic target. Here we show that OPB-51602, small molecule inhibitor of STAT3, highly toxic STAT3- dependent manner. Specifically, drug toxicity depends on as tumor cells expressing only mitochondrially-restricted form are...
Transplantation of hematopoietic material into recipient mice is an assay routinely used to determine the presence and function stem progenitor cells (HSPCs) in vivo . The principle method transplant donor being tested for HSPCs a mouse following bone marrow ablation testing reconstitution hematopoiesis. Congenic strains where differ by distinct cell surface antigen (commonly CD45.1 versus CD45.2) are distinguish between derived from any residual cells. Typically, transplantation performed...
Abstract Maintenance of immune homeostasis involves a synergistic relationship between the host and microbiome. Canonical interferon (IFN) signaling controls responses to acute microbial infection, through engagement STAT1 transcription factor. However, contribution tonic levels IFN in absence infection remains largely unexplored. We report that KO mice spontaneously developed an inflammatory disease marked by myeloid hyperplasia splenic accumulation hematopoietic stem cells. Moreover, these...