A5102952100- DNA Repair Mechanisms
- Cancer-related Molecular Pathways
- Epigenetics and DNA Methylation
- Genetic factors in colorectal cancer
- Hematopoietic Stem Cell Transplantation
- Cancer Genomics and Diagnostics
- Connective Tissue Growth Factor Research
- Cytokine Signaling Pathways and Interactions
- interferon and immune responses
- T-cell and Retrovirus Studies
- PARP inhibition in cancer therapy
- T-cell and B-cell Immunology
- Cell death mechanisms and regulation
- Medicinal Plant Pharmacodynamics Research
- Pluripotent Stem Cells Research
- CRISPR and Genetic Engineering
- Biomarkers in Disease Mechanisms
- RNA modifications and cancer
- Parasitic Infections and Diagnostics
- Viral-associated cancers and disorders
- Kruppel-like factors research
- Protein Degradation and Inhibitors
- Retinal Development and Disorders
- HIV-related health complications and treatments
- Cardiovascular Function and Risk Factors
Case Western Reserve University
2012-2024
University Hospitals Seidman Cancer Center
2013-2018
University Hospitals Cleveland Medical Center
2008-2016
Case Comprehensive Cancer Center
2016
Institute for Stem Cell Biology and Regenerative Medicine
2007
Cleveland Clinic
2003-2004
University School
2004
Significance Pressure overload triggers responses in cardiomyocytes and noncardiomyocytes, leading to pressure hypertrophy (POH). Here, we show that cardiac resident macrophages regulate compensatory myocardial adaptation POH, while nonresident infiltrating are detrimental. At early-phase induces macrophage proliferation, which is regulated by Kruppel-like factor 4. late-phase also Ly6C hi monocyte infiltration, its blockade improves angiogenesis preserves function. Mechanistically, the...
Interferon-gamma (IFNgamma) is a pluripotent cytokine whose major biological effects are mediated through pathway in which STAT1 the predominant and essential transcription factor. STAT3 can also be activated weakly by IFNgamma, but mechanism of activation function as part interferon response not known. Here we show that much stronger more prolonged STAT1-null mouse embryo fibroblasts than wild-type cells. In to SRC-family kinases required activate (but STAT1) tyrosine phosphorylation,...
Abdominal aortic aneurysm (AAA) is a major cause of morbidity and mortality; however, the mechanisms that are involved in disease initiation progression incompletely understood. Extracellular matrix proteins play an integral role modulating vascular homeostasis health disease. Here, we determined expression matricellular protein CCN3 strongly reduced rodent AAA models, including angiotensin II–induced elastase perfusion–stimulated AAA. levels were also human biopsies compared with those...
Suppressor of cytokine signaling (SOCS)-1, the key negative regulator interferon (IFN)-γ-dependent signaling, is induced in response to IFNγ. SOCS-1 binds and inhibits IFNγ receptor-associated kinase Janus-activated (JAK) 2 its function vitro, but mechanism by which IFNγ-dependent vivo not clear. Upon stimulation, mouse receptor subunit 1 (IFNGR1) phosphorylated on several cytoplasmic tyrosine residues, Tyr419 required for signal transducer activator transcription (STAT) activation embryo...
Abstract Substantial evidence implicates crosstalk between metabolic tissues and the immune system in inception progression of obesity. However, molecular regulators that orchestrate metaflammation both centrally peripherally remains incompletely understood. Here, we identify myeloid Krüppel-like factor 2 (KLF2) as an essential regulator obesity its sequelae. In mice humans, consumption a fatty diet downregulates KLF2 levels. Under basal conditions, myeloid-specific knockout (K2KO) exhibit...
// Yan 1 , Xiangzi Han Yulan Qing 2 Allison G. Condie 3 Shashank Gorityala 4 Shuming Yang Xu 2, Youwei Zhang Stanton L. Gerson Department of Pharmacology, Case Western Reserve University, Cleveland, OH, USA Hematology and Oncology, Comprehensive Cancer Center, Division Radiopharmaceutical Science, Center for Imaging Research, Radiology, Chemistry, Biomedical Engineering, Cleveland State Correspondence to: Gerson, email: slg5@case.edu Keywords: 5-fluorodeoxyuridine, base excision repair,...
Interleukin-1 (IL-1) induces the phosphorylation of Stat1 on serine 727 but not tyrosine 701. Analyses mutant I1A cells, which lack IL-1 receptor-associated kinase (IRAK), and cells reconstituted with deletion mutants IRAK show that IL-1-mediated requires protein its activity does involve phosphatidylinositol-3′-kinase (PI3K) or mitogen-activated (MAP) kinases p38 ERK. interact in vivo, this interaction is increased response to IL-1, suggesting may serve recruit as yet unknown IL-1-induced...
Hematopoietic stem cell (HSC) populations require DNA repair pathways to maintain their long-term survival and reconstitution capabilities, but mediators of these processes are still being elucidated. Exonuclease 1 (Exo1) participates in homologous recombination (HR) Exo1 loss results impaired 5' HR end resection. We use cultured Exo1(mut) fibroblasts bone marrow demonstrate that function defective cycling cells. Conversely, mice is not required for maintenance quiescent HSCs at steady...
Thymidylate synthase (TS) inhibitors including fluoropyrimidines [e.g., 5-Fluorouracil (5-FU) and 5-Fluorodeoxyuridine (5-FdU, floxuridine)] antifolates (e.g., pemetrexed) are widely used against solid tumors. Previously, we reported that shRNA-mediated knockdown (KD) of uracil DNA glycosylase (UDG) sensitized cancer cells to 5-FdU. Because p53 has also been shown as a critical determinant the sensitivity TS inhibitors, further interrogated 5-FdU cytotoxicity after UDG depletion with regard...
Abstract Background Premature aging has been identified as a global risk factor for cancer. Causes of premature are multifactorial, including inflammation, infection, chronic stress, and lifestyle factors. Method We evaluated whether in people living with HIV (PLWH) was associated antiretroviral therapy (ART) or the diagnosis used well‐established DNA methylation patterns to assess aging, using Horvath et al., individuals located Cleveland, Ohio compared these standardized datasets US...
Normal human hematopoietic stem and progenitor cells (HPC) lose expression of MLH1, an important mismatch repair (MMR) pathway gene, with age. Loss MMR leads to replication dependent mutational events microsatellite instability observed in secondary acute myelogenous leukemia other hematologic malignancies. Epigenetic CpG methylation upstream the MLH1 promoter is a contributing factor acquired loss tumors epithelia proximal mucosa. Using single molecule high-throughput bisulfite sequencing...
Whereas transformation events in hematopoietic malignancies may occur at different developmental stages, the initial mutation originates stem cells (HSCs), creating a preleukemic cell (PLSC). Subsequent mutations either or progenitor levels transform PLSC into lymphoma/leukemia initiating (LIC). Thymic lymphomas have been thought to develop from developing thymocytes. T progenitors are generated HSCs bone marrow (BM), but maturation and proliferation of as well T-lymphomagenesis depends on...
Abstract One of the major health concerns on long-duration space missions will be radiation exposure to astronauts. Outside earth's magnetosphere, astronauts exposed galactic cosmic rays (GCR) and solar particle events that are principally composed protons He, Ca, O, Ne, Si, Fe nuclei. Protons by far most common species, but higher atomic number particles thought more damaging biological systems. Evaluation amelioration risks from GCR important for deep travel. The hematopoietic system is...
The elevated level of replication stress is an intrinsic characteristic cancer cells. Targeting the mechanisms that maintain genome stability to further increase and thus induce severe instability has become a promising approach for treatment. Here, we identify histone deacetylase 8 (HDAC8) as drug target whose inactivation synergizes with inhibition checkpoint kinases elicit substantial compromise integrity selectively in We showed simultaneous HDAC8 led extensive fork collapse,...
Abstract Thymic lymphomas have been thought to develop from disregulated differentiation and proliferation of developing thymocytes. T cell progenitors are generated hematopoietic stem cells (HSCs) in the bone marrow (BM). Recent evidence strongly suggests that whereas transformation events may occur at different developmental stages, initial mutation originates HSCs, creates a preleukemic (PLSC). Subsequent mutations either or progenitor levels would transform PLSC into lymphoma/leukemia...
Background: Structural components within the vasculature, including extracellular matrix proteins, play an integral role in modulating vascular homeostasis health and disease. Previous studies have identified important roles of a family secreted associated proteins termed CCN (Cyr61, Ctgf, Nov) mediating homeostasis. However, for this initiation / progression diseases remains undetermined. Methods Results: Herein, biochemical genetic gain- loss-of function reveal novel CCN3 (a member family)...