A5024894867- Acute Myeloid Leukemia Research
- Neurofibromatosis and Schwannoma Cases
- Neuroblastoma Research and Treatments
- Mast cells and histamine
- melanin and skin pigmentation
- Genomics and Phylogenetic Studies
- Nerve injury and regeneration
- Sarcoma Diagnosis and Treatment
- RNA modifications and cancer
- Protein Degradation and Inhibitors
- Histone Deacetylase Inhibitors Research
- RNA Research and Splicing
- Immune Response and Inflammation
- Gene expression and cancer classification
- Ubiquitin and proteasome pathways
- Multiple Myeloma Research and Treatments
- Machine Learning in Bioinformatics
- interferon and immune responses
- Cancer, Hypoxia, and Metabolism
- Epigenetics and DNA Methylation
- Catalytic Processes in Materials Science
- Aluminum Alloys Composites Properties
- NF-κB Signaling Pathways
- Cancer-related molecular mechanisms research
- RNA and protein synthesis mechanisms
Cincinnati Children's Hospital Medical Center
2016-2025
University of Cincinnati Medical Center
2018-2024
Laboratoire d’immunologie intégrative du cancer
2024
Yonsei University
2021-2024
University of Cincinnati
2016-2022
The University of Texas MD Anderson Cancer Center
2017
Kookmin University
2014-2016
Indiana University Bloomington
2006-2015
Soonchunhyang University
2014
Soonchunhyang University Hospital
2014
MicroRNAs (miRNAs) are small (19–24 nt), nonprotein-coding nucleic acids that regulate specific 'target' gene products via hybridization to mRNA transcripts, resulting in translational blockade or transcript degradation. Although miRNAs have been implicated numerous developmental and adult diseases, their impact on biological pathways cellular phenotypes, addition miRNA promoter regulation, remain largely unknown. To improve facilitate research of functions we developed MMIA (microRNA...
Dysregulation of innate immune signaling is a hallmark hematologic malignancies. Recent therapeutic efforts to subvert aberrant in myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) have focused on the kinase IRAK4. IRAK4 inhibitors achieved promising, though moderate, responses preclinical studies clinical trials for MDS AML. The reasons underlying limited remain unknown. In this study, we reveal that inhibiting leukemic cells elicits functional complementation compensation by...
Genetic changes required for the formation and progression of human Schwann cell tumors remain elusive. Using a Sleeping Beauty forward genetic screen, we identified several genes involved in canonical Wnt signaling as potential drivers benign neurofibromas malignant peripheral nerve sheath (MPNSTs). In MPNSTs, activation increased with tumor grade was associated downregulation β-catenin destruction complex members or overexpression ligand that potentiates signaling, R-spondin 2 (RSPO2)....
Immune stress pathways drive resistance to FLT3 inhibition in FLT3-mutant AML, but a dual inhibitor of and IRAK1/4 overcomes this resistance.
In neurofibromatosis type 1 (NF1) and in highly aggressive malignant peripheral nerve sheath tumors (MPNSTs), constitutively active RAS-GTP increased MAPK signaling are important tumorigenesis. Dual specificity phosphatases (DUSPs) negative regulators of that dephosphorylate p38, JNK, ERK different settings. Although often acting as tumor suppressors, DUSPs may also act oncogenes, helping cells adapt to high levels signaling. We hypothesized inhibiting might be selectively toxic from...
Highlights•TRAF6 is required for hematopoietic stem cell (HSC) homeostasis•TRAF6 regulates HSC quiescence, self-renewal, and differentiation•Deletion of TRAF6 results in loss fitness•TRAF6 maintains a minimal threshold level IKKβ/NF-κB signaling HSCSummaryBasal nuclear factor κB (NF-κB) activation homeostasis the absence inflammation; however, upstream mediators basal NF-κB are less well understood. Here, we describe as an essential regulator through NF-κB. Hematopoietic-specific deletion...
Abstract Background Diffuse intrinsic pontine gliomas (DIPGs) are highly lethal childhood brain tumors. Their unique genetic makeup, pathological heterogeneity, and brainstem location all present challenges to treatment. Developing mouse models that accurately reflect each of these distinct features will be critical advance our understanding DIPG development, progression, therapeutic resistance. The aim this study was generate new DIPG, characterize the role specific oncogenic combinations...
The lipogenic enzyme stearoyl CoA desaturase (SCD) plays a key role in tumor lipid metabolism and membrane architecture. SCD is often up-regulated therapeutic target cancer. Here, we report the unexpected finding that median expression of low glioblastoma relative to normal brain due hypermethylation unintentional monoallelic co-deletion with phosphatase tensin homolog (PTEN) subset patients. Cell lines from this expressed undetectable SCD, yet retained residual enzymatic activity....
To define alterations early in tumor formation, we studied nerve tumors neurofibromatosis 1 (NF1), a predisposition syndrome. Affected individuals develop neurofibromas, benign driven by NF1 loss Schwann cells (SCs). By comparing normal to plexiform neurofibroma (PN) using single-cell and bulk RNA sequencing, identified changes 5 SC populations, including de novo progenitor–like (SCP-like) population. Long after Nf1 loss, populations developed PN-specific expression of Dcn, Postn, Cd74, with...
To identify genes and signaling pathways that initiate Neurofibromatosis type 1 (NF1) neurofibromas, we used unbiased insertional mutagenesis screening, mouse models, molecular analyses. We mapped an Nf1-Stat3-Arid1b/β-catenin pathway becomes active in the context of Nf1 loss. Genetic deletion Stat3 Schwann cell progenitors (SCPs) cells (SCs) prevents neurofibroma formation, decreasing SCP self-renewal β-catenin activity. expression rescues effects loss SCPs. Importantly, P-STAT3 correlate...
Successful treatment of neurofibromatosis type 1 (NF1)-associated tumors poses a significant clinical challenge. While the primary underlying genetic defect driving RAS signaling is well described, recent evidence suggests immune dysfunction contributes to tumor pathogenesis and malignant transformation. As immunologic characterizations, prognostic predictive immunotherapeutic response in other cancers, are not fully described for benign NF1-related tumors, we sought define their profiles....
Abstract Neurofibromas are benign peripheral nerve tumors driven by NF1 loss in Schwann cells (SCs). Macrophages abundant neurofibromas, and macrophage targeted interventions may have therapeutic potential these tumors. We generated gene expression data from fluorescence-activated cell sorted (FACS) SCs macrophages wild-type mutant neurofibroma to identify candidate pathways involved SC-macrophage cross-talk. While 1-month-old Nf1 neither nor significantly differed their normal counterparts,...
Dysregulation of innate immune signaling pathways is implicated in various hematologic malignancies. However, these have not been systematically examined acute myeloid leukemia (AML). We report that AML hematopoietic stem and progenitor cells (HSPCs) exhibit a high frequency dysregulated immune-related inflammatory pathways, referred to as oncogenic states. Through gene expression analyses functional studies human cell lines patient-derived samples, we found the ubiquitin-conjugating enzyme...
Myelodysplastic syndromes (MDS) are heterogeneous hematopoietic disorders that incurable with conventional therapy. Their incidence is increasing global population aging. Although many genetic, epigenetic, splicing, and metabolic aberrations have been identified in patients MDS, their clinical features quite similar. Here, we show hypoxia-independent activation of hypoxia-inducible factor 1α (HIF1A) signaling both necessary sufficient to induce dysplastic cytopenic MDS phenotypes. The HIF1A...
The use of microarrays and RNA-seq technologies is ubiquitous for transcriptome analyses in modern biology. With proper analysis tools, the differential gene expression process can be significantly accelerated. Many open-source programs provide cutting-edge techniques, but these often require programming skills lack intuitive interactive or graphical user interfaces. To avoid bottlenecks impeding seamless processing, we have developed an Interactive Gene Expression Analysis Kit, term iGEAK,...