Inflammatory responses of vascular cells

Summary

Principal Investigator: Paul L Fox
Abstract: Chronic inflammation is a principal cause of atherosclerosis and other vascular diseases. Inflammation is an orchestrated response to trauma incited by tissue injury or microbial invasion of the host. The inflammatory response is initiated by cytokines that induce cascades of signaling events culminating in the expression of new gene products, some of them toxic to invading organisms. Uncontrolled production or accumulation of inflammatory products can be injurious to the host organism. Mechanisms have evolved that limit the production of these products and permit resolution of the inflammatory response. The central hypothesis of this continuing Program Project is that pro- and anti-inflammatory processes in vascular cells are tightly regulated by endogenous signaling pathways, and their dysregulation contributes to vascular diseases such as atherosclerosis. We will investigate this hypothesis through three highly focused, but well-integrated projects led by a team of accomplished experts in diverse areas of vascular inflammation. In Project 1, Dr. Xiaoxia Li investigates the macrophage signaling pathways initiated by the interleukin-1R (IL-1 receptor)/TLR (Toll-like receptor) superfamily which can lead to either a pro-inflammatory, transcriptional program of gene expression, or an anti-inflammatory, post-transcriptional program. The theme of pro- and anti-inflammation, and also post-transcriptional regulation, continues in Project 2, led by Dr. Paul Fox, which focuses on a distinct post-transcriptional mechanism in monocyte/macrophages in which interferon-??induces phosphorylation- dependent formation of a complex that binds select inflammatory transcripts and inhibits their translation. The goal of Project 3, led by Dr. Paul DiCorleto, is to understand the role of the tumor necrosis factor receptor p75 and the transcription factor HOXA9 in the transcriptional regulation of pro-inflammatory genes in endothelial cells. Three scientific cores (Cell Culture, Atherosclerosis and Lipoprotein Analysis, and Macromolecular Interaction) and an Administration Core will provide multi-project support, expertise, and service in a cost-effective manner, which will significantly strengthen each investigator's research effort.
Funding Period: 1997-07-01 - 2015-03-31
more information: NIH RePORT

Top Publications

  1. pmc MyD88-dependent interplay between myeloid and endothelial cells in the initiation and progression of obesity-associated inflammatory diseases
    Minjia Yu
    Department of Immunology, 2 Department of Cellular and Molecular Medicine, 3 Department of Pathobiology, 4 Department of Molecular Cardiology, Cleveland Clinic, Cleveland, OH 44195
    J Exp Med 211:887-907. 2014
  2. pmc β-TrCP-mediated IRAK1 degradation releases TAK1-TRAF6 from the membrane to the cytosol for TAK1-dependent NF-κB activation
    Wei Cui
    State Key Laboratory of Protein and Plant Gene Research, LSC, Peking University, Beijing, China
    Mol Cell Biol 32:3990-4000. 2012
  3. pmc Myo1c facilitates G-actin transport to the leading edge of migrating endothelial cells
    Yi Fan
    Department of Cell Biology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA
    J Cell Biol 198:47-55. 2012
  4. pmc Protection of extraribosomal RPL13a by GAPDH and dysregulation by S-nitrosylation
    Jie Jia
    Department of Cell Biology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA
    Mol Cell 47:656-63. 2012
  5. pmc Pellino 2 is critical for Toll-like receptor/interleukin-1 receptor (TLR/IL-1R)-mediated post-transcriptional control
    Tae Whan Kim
    Department of Immunology, Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA
    J Biol Chem 287:25686-95. 2012
  6. pmc Coding region polyadenylation generates a truncated tRNA synthetase that counters translation repression
    Peng Yao
    Department of Cell Biology, The Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA
    Cell 149:88-100. 2012
  7. pmc Protective role of macrophage-derived ceruloplasmin in inflammatory bowel disease
    Bakytzhan Bakhautdin
    Department of Cell Biology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA
    Gut 62:209-19. 2013
  8. pmc HOXA9 methylation by PRMT5 is essential for endothelial cell expression of leukocyte adhesion molecules
    Smarajit Bandyopadhyay
    Department of Cell Biology, Lerner Research Institute and Cleveland Clinic Lerner College of Medicine, Cleveland Clinic Foundation, Cleveland, Ohio, USA
    Mol Cell Biol 32:1202-13. 2012
  9. pmc T cell-derived Act1 is necessary for IL-25-mediated Th2 responses and allergic airway inflammation
    Shadi Swaidani
    Department of Immunology, Cleveland Clinic, Cleveland, OH 44195, USA
    J Immunol 187:3155-64. 2011
  10. pmc Repression of VEGFA by CA-rich element-binding microRNAs is modulated by hnRNP L
    Faegheh Jafarifar
    Department of Cell Biology, The Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA
    EMBO J 30:1324-34. 2011

Research Grants

  1. CENTER FOR GASTROINTESTINAL BIOLOGY AND DISEASE
    Robert S Sandler; Fiscal Year: 2013
  2. EARLY EVENTS IN ALZHEIMER PATHOGENESIS
    SUE TILTON GRIFFIN; Fiscal Year: 2013

Detail Information

Publications56

  1. pmc MyD88-dependent interplay between myeloid and endothelial cells in the initiation and progression of obesity-associated inflammatory diseases
    Minjia Yu
    Department of Immunology, 2 Department of Cellular and Molecular Medicine, 3 Department of Pathobiology, 4 Department of Molecular Cardiology, Cleveland Clinic, Cleveland, OH 44195
    J Exp Med 211:887-907. 2014
    ..Collectively, these results implicate a critical MyD88-dependent interplay between myeloid and endothelial cells in the initiation and progression of obesity-associated inflammatory diseases. ..
  2. pmc β-TrCP-mediated IRAK1 degradation releases TAK1-TRAF6 from the membrane to the cytosol for TAK1-dependent NF-κB activation
    Wei Cui
    State Key Laboratory of Protein and Plant Gene Research, LSC, Peking University, Beijing, China
    Mol Cell Biol 32:3990-4000. 2012
    ..Taken together, these results implicate a positive role of β-TrCP-mediated IRAK1 degradation in IL-1-induced TAK1 activation...
  3. pmc Myo1c facilitates G-actin transport to the leading edge of migrating endothelial cells
    Yi Fan
    Department of Cell Biology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA
    J Cell Biol 198:47-55. 2012
    ..In addition, there is no obvious requirement for myosin II contractile-based transport of G-actin in ECs. Thus, Myo1c-facilitated G-actin transport might be a critical node for control of cell polarity and motility...
  4. pmc Protection of extraribosomal RPL13a by GAPDH and dysregulation by S-nitrosylation
    Jie Jia
    Department of Cell Biology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA
    Mol Cell 47:656-63. 2012
    ....
  5. pmc Pellino 2 is critical for Toll-like receptor/interleukin-1 receptor (TLR/IL-1R)-mediated post-transcriptional control
    Tae Whan Kim
    Department of Immunology, Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA
    J Biol Chem 287:25686-95. 2012
    ..Taken together, this study demonstrated that Pellino 2 plays a critical role for TLR/IL-1R-mediated post-transcriptional control...
  6. pmc Coding region polyadenylation generates a truncated tRNA synthetase that counters translation repression
    Peng Yao
    Department of Cell Biology, The Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA
    Cell 149:88-100. 2012
    ..Genome-wide analysis revealed multiple candidate PAY(∗) targets, including the authenticated target RRM1, suggesting a general mechanism for production of C terminus-truncated regulatory proteins...
  7. pmc Protective role of macrophage-derived ceruloplasmin in inflammatory bowel disease
    Bakytzhan Bakhautdin
    Department of Cell Biology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA
    Gut 62:209-19. 2013
    ..The goal is to understand the role of ceruloplasmin in colitis progression in a genetically modified murine model...
  8. pmc HOXA9 methylation by PRMT5 is essential for endothelial cell expression of leukocyte adhesion molecules
    Smarajit Bandyopadhyay
    Department of Cell Biology, Lerner Research Institute and Cleveland Clinic Lerner College of Medicine, Cleveland Clinic Foundation, Cleveland, Ohio, USA
    Mol Cell Biol 32:1202-13. 2012
    ..In summary, PRMT5 is a critical coactivator component in a newly defined, HOXA9-containing transcription complex. Moreover, stimulus-dependent methylation of HOXA9 is essential for ELAM expression during the EC inflammatory response...
  9. pmc T cell-derived Act1 is necessary for IL-25-mediated Th2 responses and allergic airway inflammation
    Shadi Swaidani
    Department of Immunology, Cleveland Clinic, Cleveland, OH 44195, USA
    J Immunol 187:3155-64. 2011
    ....
  10. pmc Repression of VEGFA by CA-rich element-binding microRNAs is modulated by hnRNP L
    Faegheh Jafarifar
    Department of Cell Biology, The Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA
    EMBO J 30:1324-34. 2011
    ..These studies may contribute to provide miRNA-based anticancer therapeutic tools...
  11. pmc The kinase activity of interleukin-1 receptor-associated kinase 2 is essential for lipopolysaccharide-mediated cytokine and chemokine mRNA stability and translation
    Weiguo Yin
    Department of Microbiology and Immunology, University of South China, Hengyang Hunan, China
    J Interferon Cytokine Res 31:415-22. 2011
    ....
  12. pmc The critical role of IL-1 receptor-associated kinase 4-mediated NF-κB activation in modified low-density lipoprotein-induced inflammatory gene expression and atherosclerosis
    Tae Whan Kim
    Department of Immunology, Learner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA
    J Immunol 186:2871-80. 2011
    ....
  13. pmc CNS Autoimmune Inflammation: RICK Must NOD!
    Zizhen Kang
    Department of Immunology, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH 44195, USA
    Immunity 34:3-5. 2011
    ..2011) report that the NOD-RICK signaling axis is required for the activation of dendritic cells infiltrating the central nervous system, leading to reactivation of antigen-specific T cells and autoimmune inflammation...
  14. pmc Stimulus-dependent phosphorylation of profilin-1 in angiogenesis
    Yi Fan
    Department of Cell Biology, Lerner Research Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, Ohio 44195, USA
    Nat Cell Biol 14:1046-56. 2012
    ....
  15. pmc Heterotrimeric GAIT complex drives transcript-selective translation inhibition in murine macrophages
    Abul Arif
    Department of Cellular and Molecular Medicine, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, USA
    Mol Cell Biol 32:5046-55. 2012
    ..Thus, translational control by the heterotrimeric GAIT complex in mice exemplifies the distinctive species-specific responses of myeloid cells to inflammatory stimuli...
  16. pmc Signal integration and gene induction by a functionally distinct STAT3 phosphoform
    Matthew S Waitkus
    Department of Cellular and Molecular Medicine, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, USA
    Mol Cell Biol 34:1800-11. 2014
    ....
  17. pmc Mitogen-activated protein kinase phosphatase-1 promotes neovascularization and angiogenic gene expression
    Joel D Boerckel
    From the Department of Cellular and Molecular Medicine, Lerner Research Institute, Cleveland Clinic, OH J D B, U M C, M S W, E G T, R B, P E D and Department of Aerospace and Mechanical Engineering, University of Notre Dame, IN J D B
    Arterioscler Thromb Vasc Biol 34:1020-31. 2014
    ..The purpose of this study was to evaluate the role of MKP-1 in neovascularization in vivo and identify associated mechanisms in endothelial cells...
  18. pmc The HILDA complex coordinates a conditional switch in the 3'-untranslated region of the VEGFA mRNA
    Peng Yao
    Department of Cellular and Molecular Medicine, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, USA
    PLoS Biol 11:e1001635. 2013
    ..We propose the VEGFA RNA switch as an archetype for signal-activated, protein-directed, multi-element RNA switches that regulate posttranscriptional gene expression in complex environments. ..
  19. pmc Release of nonmuscle myosin II from the cytosolic domain of tumor necrosis factor receptor 2 is required for target gene expression
    Unni M Chandrasekharan
    Department of Cellular and Molecular Medicine, Cleveland Clinic Lerner Research Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195, USA
    Sci Signal 6:ra60. 2013
    ..Thus, our findings have revealed a previously uncharacterized, noncanonical regulatory function of myosin in cytokine signaling. ..
  20. pmc Gβγ-independent recruitment of G-protein coupled receptor kinase 2 drives tumor necrosis factor α-induced cardiac β-adrenergic receptor dysfunction
    Neelakantan T Vasudevan
    Department of Molecular Cardiology, Lerner Research Institute, Cleveland Clinic, 9500 Euclid Ave, Cleveland, OH 44195, USA
    Circulation 128:377-87. 2013
    ..Proinflammatory cytokine tumor necrosis factor-α (TNFα) induces β-adrenergic receptor (βAR) desensitization, but mechanisms proximal to the receptor in contributing to cardiac dysfunction are not known...
  21. pmc Identification of nucleotides and amino acids that mediate the interaction between ribosomal protein L30 and the SECIS element
    Abby L Bifano
    Department of Cellular and Molecular Medicine, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA
    BMC Mol Biol 14:12. 2013
    ..Previous studies showed that L30 and SBP2 compete for binding to the SECIS in vitro. The SBP2:SECIS interaction has been characterized but much less is known about how L30 recognizes the SECIS...
  22. pmc STAT3-mediated coincidence detection regulates noncanonical immediate early gene induction
    Matthew S Waitkus
    Department of Cellular and Molecular Medicine, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA
    J Biol Chem 288:11988-2003. 2013
    ..Collectively, our results describe a novel regulatory mechanism in which combinatorial EGFR/PAR-1 signaling regulates STAT3-dependent IEG induction and endothelial cell migration...
  23. pmc Aminoacyl-tRNA synthetases in medicine and disease
    Peng Yao
    Department of Cellular and Molecular Medicine, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA
    EMBO Mol Med 5:332-43. 2013
    ..Here, we summarize the roles of ARSs in human diseases and medicine, focusing on the most recent and exciting discoveries...
  24. pmc Citric acid cycle and the origin of MARS
    Sandeepa M Eswarappa
    Department of Cellular and Molecular Medicine, Lerner Research Institute, Cleveland Clinic, 9500 Euclid Avenue NC10, Cleveland, OH 44195, USA
    Trends Biochem Sci 38:222-8. 2013
    ....
  25. pmc IRAK-M mediates Toll-like receptor/IL-1R-induced NFκB activation and cytokine production
    Hao Zhou
    Department of Immunology, Cleveland Clinic Foundation, Cleveland, OH 44195, USA
    EMBO J 32:583-96. 2013
    ....
  26. pmc Regulation and dysregulation of 3'UTR-mediated translational control
    Jie Jia
    Department of Cellular and Molecular Medicine, Lerner Research Institute, Cleveland Clinic, 9500 Euclid Avenue NC10, Cleveland, OH 44195, USA
    Curr Opin Genet Dev 23:29-34. 2013
    ..Here, we briefly review a few recent and representative discoveries of 3'UTR-mediated translational control, emphasizing the novel aspects of these regulatory mechanisms and their potential pathophysiological significance...
  27. pmc Inactivation of the enzyme GSK3α by the kinase IKKi promotes AKT-mTOR signaling pathway that mediates interleukin-1-induced Th17 cell maintenance
    Muhammet F Gulen
    Department of Immunology, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH 44195, USA
    Immunity 37:800-12. 2012
    ..Thus, IKKi has a critical role in Th17 cell maintenance and/or proliferation through the GSK-AKT-mTOR pathway, implicating the potential of IKKi as a therapeutic target...
  28. pmc Phosphorylation of glutamyl-prolyl tRNA synthetase by cyclin-dependent kinase 5 dictates transcript-selective translational control
    Abul Arif
    Department of Cell Biology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA
    Proc Natl Acad Sci U S A 108:1415-20. 2011
    ..Our study reveals a unique role of Cdk5/p35 in activation of the major noncanonical function of EPRS, namely translational control of macrophage inflammatory gene expression...
  29. pmc Evolution of function of a fused metazoan tRNA synthetase
    Partho Sarothi Ray
    Department of Cell Biology, Lerner Research Institute, Cleveland Clinic, USA
    Mol Biol Evol 28:437-47. 2011
    ..These results suggest that alternative splicing of WHEP domains in the EPRS gene of the cnidarian-bilaterian ancestor gave rise to a novel molecular function of EPRS conserved during metazoan evolution...
  30. doi Adenosine prompts the heart to recruit endothelial progenitors
    Jianzhong Shen
    Circ Res 102:280-2. 2008
  31. ncbi ADP stimulates human endothelial cell migration via P2Y1 nucleotide receptor-mediated mitogen-activated protein kinase pathways
    Jianzhong Shen
    Department of Cell Biology, Lerner Research Institute, Cleveland Clinic Lerner College of Medicine, Cleveland Clinic Foundation, 9500 Euclid Ave, Cleveland, OH 44195, USA
    Circ Res 102:448-56. 2008
    ..We conclude that ADP promotes human endothelial cell migration by activating P2Y1 receptor-mediated MAPK pathways, possibly contributing to reendothelialization and angiogenesis after vascular injury...
  32. pmc Absence of CD36 protects against atherosclerosis in ApoE knock-out mice with no additional protection provided by absence of scavenger receptor A I/II
    Sai Kuchibhotla
    Department of Cell Biology, Cleveland Clinic, 9500 Euclid Ave, NC 10, Cleveland, OH 44195, USA
    Cardiovasc Res 78:185-96. 2008
    ..This study addresses the effect of combined absence of scavenger receptors CD36 and SRA I/II on atherosclerosis lesion development in the apolipoprotein E knock-out (apoE degrees ) model...
  33. ncbi VEGF and thrombin induce MKP-1 through distinct signaling pathways: role for MKP-1 in endothelial cell migration
    Corttrell M Kinney
    Department of Cell Biology, Lerner Research Institute and Cleveland Clinic Lerner College of Medicine, Cleveland, Ohio, USA
    Am J Physiol Cell Physiol 294:C241-50. 2008
    ..Overall, these results demonstrate distinct MAPK signaling pathways for thrombin versus VEGF induction of MKP-1 in ECs and point to the importance of MKP-1 induction in VEGF-stimulated EC migration...
  34. ncbi Altered RNA binding activity underlies abnormal thyroid hormone metabolism linked to a mutation in selenocysteine insertion sequence-binding protein 2
    Jodi L Bubenik
    Department of Cell Biology, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio 44195, USA
    J Biol Chem 282:34653-62. 2007
    ..We hypothesize that the selective loss of a subset of selenoproteins, including some involved in thyroid hormone homeostasis, is responsible for the abnormal thyroid hormone metabolism previously observed in the affected individuals...
  35. pmc A post-transcriptional pathway represses monocyte VEGF-A expression and angiogenic activity
    Partho Sarothi Ray
    Department of Cell Biology, The Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA
    EMBO J 26:3360-72. 2007
    ....
  36. ncbi Signal transducer and activator of transcription 1 is required for optimal foam cell formation and atherosclerotic lesion development
    Sudesh Agrawal
    Department of Cell Biology, Cleveland Clinic Foundation, 9500 Euclid Ave, Cleveland, OH 44195, USA
    Circulation 115:2939-47. 2007
    ..The present study investigated a novel role for Stat1 in foam cell formation and atherosclerosis...
  37. pmc HOXA9 participates in the transcriptional activation of E-selectin in endothelial cells
    Smarajit Bandyopadhyay
    Department of Cell Biology, Lerner Research Institute and Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland Clinic Foundation, Cleveland, OH 44195, USA
    Mol Cell Biol 27:4207-16. 2007
    ..Further, we provide evidence that HOXA9 acts as an obligate proinflammatory factor by mediating cytokine induction of E-selectin...
  38. ncbi Decreased atherosclerosis in mice deficient in tumor necrosis factor-alpha receptor-II (p75)
    Unni M Chandrasekharan
    Arterioscler Thromb Vasc Biol 27:e16-7. 2007
  39. pmc L13a blocks 48S assembly: role of a general initiation factor in mRNA-specific translational control
    Purvi Kapasi
    Department of Biological, Geological, and Environmental Sciences, Cleveland State University, Cleveland, OH 44115, USA
    Mol Cell 25:113-26. 2007
    ..However, our studies reveal a unique mechanism in which targeting of eIF4G by mRNA-bound L13a elicits transcript-specific translational repression...
  40. ncbi Quantitative assay for mouse atherosclerosis in the aortic root
    Julie Baglione
    Department of Cell Biology, The Cleveland Clinic Foundation, OH, USA
    Methods Mol Med 129:83-95. 2006
    ..Here, we provide the detailed methods for the quantitative analysis of mouse aortic root lesion area...
  41. pmc Tumor necrosis factor alpha (TNF-alpha) receptor-II is required for TNF-alpha-induced leukocyte-endothelial interaction in vivo
    Unni M Chandrasekharan
    Department of Cell Biology, Lerner Research Institute and Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland Clinic Foundation, OH 44195, USA
    Blood 109:1938-44. 2007
    ..Our findings may contribute to the identification of novel p75-targeted therapeutic approaches for inflammatory diseases...
  42. pmc WHEP domains direct noncanonical function of glutamyl-Prolyl tRNA synthetase in translational control of gene expression
    Jie Jia
    Department of Cell Biology, The Lerner Research Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195, USA
    Mol Cell 29:679-90. 2008
    ..Our results establish the essentiality of WHEP domains in the noncanonical function of EPRS in regulating inflammatory gene expression...
  43. pmc DAPK-ZIPK-L13a axis constitutes a negative-feedback module regulating inflammatory gene expression
    Rupak Mukhopadhyay
    Department of Cell Biology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA
    Mol Cell 32:371-82. 2008
    ..We propose that the module presents an important checkpoint in the macrophage "resolution of inflammation" program, and that pathway defects may contribute to chronic inflammatory disorders...
  44. pmc Synergistic induction of mitogen-activated protein kinase phosphatase-1 by thrombin and epidermal growth factor requires vascular endothelial growth factor receptor-2
    Unni M Chandrasekharan
    Department of Cell Biology, Cleveland Clinic Lerner Research Institute, Cleveland, Ohio 44195, USA
    Arterioscler Thromb Vasc Biol 30:1983-9. 2010
    ..To determine the molecular mechanism underlying the synergistic response of mitogen-activated protein kinase phosphatase-1 (MKP-1), which is induced by thrombin and epidermal growth factor (EGF)...
  45. pmc The single IgG IL-1-related receptor controls TLR responses in differentiated human intestinal epithelial cells
    Mohammed A Khan
    Division of Pediatric Gastroenterology, BC Children s Hospital, Vancouver, British Columbia V6H 3V4, Canada
    J Immunol 184:2305-13. 2010
    ..Our findings show that Sigirr broadly regulates innate responses in differentiated human IECs; therefore, it may modulate epithelial involvement in infectious and inflammatory bowel diseases...
  46. pmc Lack of mitogen-activated protein kinase phosphatase-1 protects ApoE-null mice against atherosclerosis
    Jianzhong Shen
    Department of Cell Biology, Lerner Research Institute, Cleveland Clinic Foundation, Ohio 44195, USA
    Circ Res 106:902-10. 2010
    ..Multiple protein kinases have been implicated in cardiovascular disease; however, little is known about the role of their counterparts: the protein phosphatases...
  47. pmc Thrombin induces endothelial arginase through AP-1 activation
    Weifei Zhu
    Department of Cell Biology, The Cleveland Clinic Foundation, 9500 Euclid Ave, Cleveland, OH 44195, USA
    Am J Physiol Cell Physiol 298:C952-60. 2010
    ....
  48. pmc Novel structural determinants in human SECIS elements modulate the translational recoding of UGA as selenocysteine
    Lynda Latrèche
    Centre de Recherche de Gif sur Yvette, FRC 3115, Centre de Genetique Moleculaire, CNRS, FRE 3144, Gif sur Yvette, F 75005 Paris, France
    Nucleic Acids Res 37:5868-80. 2009
    ..Thus, the SECIS contains intrinsic information that modulates selenocysteine incorporation efficiency...
  49. pmc Two-site phosphorylation of EPRS coordinates multimodal regulation of noncanonical translational control activity
    Abul Arif
    Department of Cell Biology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA
    Mol Cell 35:164-80. 2009
    ..Thus, two-site phosphorylation provides structural and functional pliability to EPRS and choreographs the repertoire of activities that regulates inflammatory gene expression...
  50. pmc IRAK4 kinase activity is required for Th17 differentiation and Th17-mediated disease
    Kirk A Staschke
    Eli Lilly and Co, Indianapolis, IN 46285, USA
    J Immunol 183:568-77. 2009
    ..The results of these studies demonstrate that IL-1-mediated IRAK4 kinase activity in T cells is essential for induction of IL-23R expression, Th17 differentiation, and autoimmune disease...
  51. pmc Lysophosphatidylcholine activates a novel PKD2-mediated signaling pathway that controls monocyte migration
    Mingqi Tan
    Department of Pathobiology, University of Tennessee College of Veterinary Medicine, Knoxville, TN 37996, USA
    Arterioscler Thromb Vasc Biol 29:1376-82. 2009
    ..p38 MAPK mediation of lysoPC-induced monocytic cell migration was reported previously; our results reveal that the lysoPC-induced PKD2-p38 pathway controls monocyte migration...
  52. pmc Spatial coordination of actin polymerization and ILK-Akt2 activity during endothelial cell migration
    Yi Fan
    Department of Cell Biology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA
    Dev Cell 16:661-74. 2009
    ..Thus, the actin-Tbeta4 complex constitutes a latent coordinating center for cell migratory behavior, allowing profilin to initiate a cascade of events at the leading edge that couples actin polymerization to matrix degradation...
  53. pmc Known turnover and translation regulatory RNA-binding proteins interact with the 3' UTR of SECIS-binding protein 2
    Jodi L Bubenik
    Department of Cell Biology, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio 44195, USA
    RNA Biol 6:73-83. 2009
    ..The identification of CUG-BP1 and HuR as factors that bind to the SBP2 3' UTR suggests that TTR-RBPs play a role in the regulation of SBP2, which then dictates the expression of the selenoproteome...
  54. pmc A stress-responsive RNA switch regulates VEGFA expression
    Partho Sarothi Ray
    Department of Cell Biology, The Lerner Research Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, Ohio 44195, USA
    Nature 457:915-9. 2009
    ....
  55. pmc Histone H3 as a novel substrate for MAP kinase phosphatase-1
    Corttrell M Kinney
    Dept of Cell Biology, Lerner Research Institute and Cleveland Clinic Lerner College of Medicine of Case Western Reserve Univ, Cleveland Clinic, NB 21, 9500 Euclid Ave, Cleveland, OH 44195, USA
    Am J Physiol Cell Physiol 296:C242-9. 2009
    ..We propose that MKP-1-mediated H3 (phospho-Ser-10) dephosphorylation is a key regulatory step in EC activation by VEGF and thrombin...
  56. ncbi Translational control of ceruloplasmin gene expression: beyond the IRE
    Barsanjit Mazumder
    Department of Biology, Cleveland State University, Cleveland, OH, USA
    Biol Res 39:59-66. 2006
    ..Our experiments describe a new mechanism of translational control of an iron-related protein and may shed light on the role that macrophage-derived Cp plays at the intersection of iron homeostasis and inflammation...

Research Grants30

  1. CENTER FOR GASTROINTESTINAL BIOLOGY AND DISEASE
    Robert S Sandler; Fiscal Year: 2013
    ..Through all of its activities, the Center improves communication, promotes collaboration, develops careers and generally enriches the intellectual climate for digestive disease research. ..
  2. EARLY EVENTS IN ALZHEIMER PATHOGENESIS
    SUE TILTON GRIFFIN; Fiscal Year: 2013
    ..The synergy between our aims, approaches, and measures will enable us to meet our goal of defining early cellular interactions toward development of rational interventions in AD. ..