Rafeul Alam

Summary

Publications

  1. pmc A mutation in the human Uncoordinated 119 gene impairs TCR signaling and is associated with CD4 lymphopenia
    Magdalena M Gorska
    Department of Medicine, Division of Allergy and Immunology, National Jewish Health, 1400 Jackson St, Denver, CO 80206, USA
    Blood 119:1399-406. 2012
  2. pmc Mitogen-activated protein kinase signalling and ERK1/2 bistability in asthma
    R Alam
    Department of Medicine, Division of Allergy and Immunology, National Jewish Health, Denver, CO 80206, USA
    Clin Exp Allergy 41:149-59. 2011
  3. pmc Establishment of extracellular signal-regulated kinase 1/2 bistability and sustained activation through Sprouty 2 and its relevance for epithelial function
    Weimin Liu
    Division of Allergy and Immunology, Department of Medicine, National Jewish Health, 1400 Jackson Street, Denver, CO 80206, USA
    Mol Cell Biol 30:1783-99. 2010
  4. pmc ERK1 is important for Th2 differentiation and development of experimental asthma
    Nicholas Goplen
    Division of Allergy and Immunology, National Jewish Health, 1400 Jackson Street, Denver, CO 80206, USA
    FASEB J 26:1934-45. 2012
  5. doi request reprint Uncoordinated 119 preferentially induces Th2 differentiation and promotes the development of asthma
    Magdalena M Gorska
    Division of Allergy and Immunology, Department of Medicine, National Jewish Health, Denver, CO 80206, USA
    J Immunol 184:4488-96. 2010
  6. pmc IL-2 and IL-4 stimulate MEK1 expression and contribute to T cell resistance against suppression by TGF-beta and IL-10 in asthma
    Qiaoling Liang
    Division of Allergy and Immunology, Department of Medicine and Pediatrics, National Jewish Health and University of Colorado at Denver, Denver, CO 80206, USA
    J Immunol 185:5704-13. 2010
  7. doi request reprint Uncoordinated 119 protein controls trafficking of Lck via the Rab11 endosome and is critical for immunological synapse formation
    Magdalena M Gorska
    Division of Allergy and Immunology, Department of Medicine, National Jewish Health, Denver, CO 80206, USA
    J Immunol 183:1675-84. 2009
  8. ncbi request reprint Unc119 regulates myofibroblast differentiation through the activation of Fyn and the p38 MAPK pathway
    Ramarao Vepachedu
    National Jewish Medical and Research Center and University of Colorado Health Sciences Center, Denver, CO 80206, USA
    J Immunol 179:682-90. 2007
  9. ncbi request reprint A phosphosite screen identifies autocrine TGF-beta-driven activation of protein kinase R as a survival-limiting factor for eosinophils
    Nicholas Goplen
    National Jewish Medical and Research Center, Denver, CO 80206, USA
    J Immunol 180:4256-64. 2008
  10. doi request reprint Cell-specific activation profile of extracellular signal-regulated kinase 1/2, Jun N-terminal kinase, and p38 mitogen-activated protein kinases in asthmatic airways
    Weimin Liu
    Division of Allergy and Immunology, Department of Medicine, National Jewish Medical and Research Center, Denver, CO 80206, USA
    J Allergy Clin Immunol 121:893-902.e2. 2008

Collaborators

Detail Information

Publications31

  1. pmc A mutation in the human Uncoordinated 119 gene impairs TCR signaling and is associated with CD4 lymphopenia
    Magdalena M Gorska
    Department of Medicine, Division of Allergy and Immunology, National Jewish Health, 1400 Jackson St, Denver, CO 80206, USA
    Blood 119:1399-406. 2012
    ..The mutation is not present in 2 other patients with ICL, patients with secondary CD4 lymphopenia or 60 healthy subjects. The V22G mutation of Unc119 represents a novel genetic defect in ICL...
  2. pmc Mitogen-activated protein kinase signalling and ERK1/2 bistability in asthma
    R Alam
    Department of Medicine, Division of Allergy and Immunology, National Jewish Health, Denver, CO 80206, USA
    Clin Exp Allergy 41:149-59. 2011
    ..repeated viral infection or repeated allergen exposure) seems to be a common theme in asthma and other chronic illnesses. We thus hypothesize that the self-perpetuated ERK1/2 signal plays an important role in the pathogenesis of asthma...
  3. pmc Establishment of extracellular signal-regulated kinase 1/2 bistability and sustained activation through Sprouty 2 and its relevance for epithelial function
    Weimin Liu
    Division of Allergy and Immunology, Department of Medicine, National Jewish Health, 1400 Jackson Street, Denver, CO 80206, USA
    Mol Cell Biol 30:1783-99. 2010
    ..Thus, we have developed a cellular model of sustained ERK1/2 activation, which may provide a mechanistic understanding of self-sustained biological processes in chronic illnesses such as asthma...
  4. pmc ERK1 is important for Th2 differentiation and development of experimental asthma
    Nicholas Goplen
    Division of Allergy and Immunology, National Jewish Health, 1400 Jackson Street, Denver, CO 80206, USA
    FASEB J 26:1934-45. 2012
    ..We conclude that ERK1 plays a nonredundant role in Th2 differentiation and development of experimental asthma. ERK1 controls Th2 differentiation and survival through its effect on JunB and BIM, respectively...
  5. doi request reprint Uncoordinated 119 preferentially induces Th2 differentiation and promotes the development of asthma
    Magdalena M Gorska
    Division of Allergy and Immunology, Department of Medicine, National Jewish Health, Denver, CO 80206, USA
    J Immunol 184:4488-96. 2010
    ..We speculate that the heightened expression of Unc119 promotes Th2, inhibits Th1 differentiation, and contributes to the pathogenesis of asthma in humans...
  6. pmc IL-2 and IL-4 stimulate MEK1 expression and contribute to T cell resistance against suppression by TGF-beta and IL-10 in asthma
    Qiaoling Liang
    Division of Allergy and Immunology, Department of Medicine and Pediatrics, National Jewish Health and University of Colorado at Denver, Denver, CO 80206, USA
    J Immunol 185:5704-13. 2010
    ..We have uncovered an IL-2- and IL-4-driven MEK1 induction mechanism that results in heightened ERK1/2 activation in asthmatic T cells and make them resistant to certain inhibitory mechanisms...
  7. doi request reprint Uncoordinated 119 protein controls trafficking of Lck via the Rab11 endosome and is critical for immunological synapse formation
    Magdalena M Gorska
    Division of Allergy and Immunology, Department of Medicine, National Jewish Health, Denver, CO 80206, USA
    J Immunol 183:1675-84. 2009
    ..The Unc119-regulated pathway is essential for immunological synapse formation and T cell activation...
  8. ncbi request reprint Unc119 regulates myofibroblast differentiation through the activation of Fyn and the p38 MAPK pathway
    Ramarao Vepachedu
    National Jewish Medical and Research Center and University of Colorado Health Sciences Center, Denver, CO 80206, USA
    J Immunol 179:682-90. 2007
    ..Taken together, our results suggest that Unc119 plays an important role in fibrotic processes through myofibroblast differentiation...
  9. ncbi request reprint A phosphosite screen identifies autocrine TGF-beta-driven activation of protein kinase R as a survival-limiting factor for eosinophils
    Nicholas Goplen
    National Jewish Medical and Research Center, Denver, CO 80206, USA
    J Immunol 180:4256-64. 2008
    ..Together, our findings suggest that survival of eosinophils is in part controlled by basal activation of PKR through autocrine TGF-beta and that this could be modulated by a Th2 microenvironment in vivo...
  10. doi request reprint Cell-specific activation profile of extracellular signal-regulated kinase 1/2, Jun N-terminal kinase, and p38 mitogen-activated protein kinases in asthmatic airways
    Weimin Liu
    Division of Allergy and Immunology, Department of Medicine, National Jewish Medical and Research Center, Denver, CO 80206, USA
    J Allergy Clin Immunol 121:893-902.e2. 2008
    ..Many airway cells manifest signs of chronic activation in asthma. The mechanism of this chronic activation is unknown...
  11. doi request reprint UNC119 inhibits dynamin and dynamin-dependent endocytic processes
    Zunayet Karim
    Division of Allergy and Immunology, Department of Medicine, National Jewish Health, 1400 Jackson Street, Denver, CO 80206, USA
    Cell Signal 22:128-37. 2010
    ..Thus, Unc119 regulates various endocytic pathways through dynamin and sets a threshold point for vesicular trafficking...
  12. pmc Nuclear translocation of MEK1 triggers a complex T cell response through the corepressor silencing mediator of retinoid and thyroid hormone receptor
    Lei Guo
    Division of Allergy and Immunology, Department of Medicine, National Jewish Health, Denver, CO 80206, USA
    J Immunol 190:159-67. 2013
    ..MEK1 triggers a complex pattern of early T cell activation, followed by a late inhibition through its interaction with SMRT. This biphasic dual effect most likely reflects a homeostatic regulation of T cell function by MEK1...
  13. pmc MK2 controls the level of negative feedback in the NF-kappaB pathway and is essential for vascular permeability and airway inflammation
    Magdalena M Gorska
    Division of Allergy and Immunology, Department of Medicine, National Jewish Medical and Research Center, Denver, CO 80206, USA
    J Exp Med 204:1637-52. 2007
    ..This pattern of activation is essential for many NF-kappaB-regulated genes and development of inflammation. Thus, the MK2-HSP27 pathway is an excellent target for therapeutic control of localized inflammatory diseases...
  14. pmc Combined sensitization of mice to extracts of dust mite, ragweed, and Aspergillus species breaks through tolerance and establishes chronic features of asthma
    Nicholas Goplen
    Department of Medicine, Division of Allergy and Immunology, National Jewish Health, University of Colorado Denver Health Sciences Center, Denver, CO 80206, USA
    J Allergy Clin Immunol 123:925-32.e11. 2009
    ..Existing asthma models develop tolerance when chronically exposed to the same allergen...
  15. pmc The role of low-level lactate production in airway inflammation in asthma
    Marina Ostroukhova
    National Jewish Health, Denver, CO 80206, USA
    Am J Physiol Lung Cell Mol Physiol 302:L300-7. 2012
    ..We conclude that aerobic glycolysis is increased in asthma, which promotes T cell activation. Inhibition of aerobic glycolysis blocks T cell activation and development of asthma...
  16. pmc Unc119 protects from Shigella infection by inhibiting the Abl family kinases
    Ramarao Vepachedu
    National Jewish Health, Denver, CO, USA
    PLoS ONE 4:e5211. 2009
    ..Bacteria engage cell surface receptors and intracellular signaling molecules to enter the cell. Unc119 is an adaptor protein, which interacts with receptors and tyrosine kinases. Its role in bacterial invasion of cells is unknown...
  17. ncbi request reprint JAK and Src tyrosine kinase signaling in asthma
    Kavita Tundwal
    Division of Allergy and Immunology, Department of Medicine, National Jewish Health, University of Colorado Denver, Denver, CO 80206, USA
    Front Biosci (Landmark Ed) 17:2107-21. 2012
    ..For this reason we give special attention to the tyrosine kinases that are involved in a Th2 response. Further we examine the involvement of tyrosine kinases in activation of mast cells, eosinophils and other cells...
  18. pmc Unc119, a novel activator of Lck/Fyn, is essential for T cell activation
    Magdalena M Gorska
    Division of Allergy and Immunology, Department of Internal Medicine, University of Texas Medical Branch, Galveston 77555, USA
    J Exp Med 199:369-79. 2004
    ..Reconstitution of cells with Unc119 reverses the signaling and functional outcome. Thus, Unc119 is a receptor-associated activator of Src-type kinases. It provides a novel mechanism of signal generation in the TCR complex...
  19. doi request reprint The effect of aspirin desensitization on novel biomarkers in aspirin-exacerbated respiratory diseases
    Rohit K Katial
    Division of Allergy and Immunology, National Jewish Health, Denver, CO 80206, USA
    J Allergy Clin Immunol 126:738-44. 2010
    ..Patients with aspirin-exacerbated respiratory disease have been shown to benefit clinically from aspirin desensitization followed by chronic high-dose aspirin therapy. However, the mechanism of this phenomenon is still unclear...
  20. doi request reprint Mechanisms of sustained signalling in asthma
    Christina A Christianson
    Division of Allergy and Immunology, Department of Medicine, National Jewish Health and University of Colorado Denver, Denver, Colorado 80206, USA
    Curr Opin Allergy Clin Immunol 13:100-5. 2013
    ..Here, we review data supporting the establishment of a tissue-based signalling memory utilizing examples of in-vitro, in-vivo and clinical reports of sustained extracellular signal regulated kinase 1/2 (ERK1/2) activation in asthma...
  21. ncbi request reprint A linear parametric approach for analysis of mouse respiratory impedance
    Arezoo Hanifi
    Electrical Engineering Department, University of Denver, Denver, CO 80208, USA
    IEEE Trans Biomed Circuits Syst 6:287-94. 2012
    ..Experimental findings confirm the effectiveness of the analysis technique applied here. We discuss the potential application of this method to analyses of human lung mechanics. ..
  22. doi request reprint Mechanisms of aspirin desensitization
    Trever Burnett
    Department of Allergy and Immunology, National Jewish Medical and Research Center, University of Colorado, Denver, CO 80206, USA
    Immunol Allergy Clin North Am 33:223-36. 2013
    ..In this article, the current understanding of the mechanisms of aspirin desensitization is reviewed and future areas of investigation are discussed...
  23. doi request reprint A pilot study to assess inflammatory biomarker changes when raltegravir is added to a virologically suppressive HAART regimen in HIV-1-infected patients with limited immunological responses
    Kenneth A Lichtenstein
    Division of Infectious Diseases, Department of Medicine, National Jewish Health, Denver, CO, USA
    Antivir Ther 17:1301-9. 2012
    ..Chronic inflammation from persistent immune activation could contribute to this poor response, resulting in HIV-1 disease progression and the development of some non-HIV-1 comorbidities...
  24. ncbi request reprint Consequences of a mutation in the UNC119 gene for T cell function in idiopathic CD4 lymphopenia
    Magdalena M Gorska
    Department of Medicine, Division of Allergy and Immunology, National Jewish Health, 1400 Jackson St, Denver, CO 80206, USA
    Curr Allergy Asthma Rep 12:396-401. 2012
    ..The discovery of the UNC119 defect provides a molecular mechanism for a subset of patients with this previously unexplained disease. Here we review our recent findings on the UNC119 mutation in ICL...
  25. ncbi request reprint Differential regulation of interleukin 5-stimulated signaling pathways by dynamin
    Magdalena M Gorska
    Division of Allergy and Immunology, Department of Medicine, National Jewish Medical and Research Center, Denver, Colorado 80206, USA
    J Biol Chem 281:14429-39. 2006
    ..Thus, we have identified specific functions for dynamin in the IL-5 signaling pathway and demonstrated its role in receptor endocytosis and termination of the ERK1/2 signaling pathway...
  26. pmc IL-4 confers resistance to IL-27-mediated suppression on CD4+ T cells by impairing signal transducer and activator of transcription 1 signaling
    Zhihong Chen
    Division of Allergy and Immunology, Department of Medicine, National Jewish Health, Denver, Colo Zhangshan Hospital, Fudan University, Shanghai, China
    J Allergy Clin Immunol 132:912-21.e1-5. 2013
    ..Established TH2 cells have been shown to resist reprogramming into TH1 cells. The inherent stability of TH2 cells poses a significant barrier to treating allergic diseases...
  27. pmc Inhibiting pollen reduced nicotinamide adenine dinucleotide phosphate oxidase-induced signal by intrapulmonary administration of antioxidants blocks allergic airway inflammation
    Nilesh Dharajiya
    National Heart, Lung, and Blood Institute Proteomics Center, University of Texas Medical Branch, Division of Allergy and Immunology, Department of Internal Medicine, Galveston, Texas, USA
    J Allergy Clin Immunol 119:646-53. 2007
    ..Ragweed extract (RWE) contains NADPH oxidases that induce oxidative stress in the airways independent of adaptive immunity (signal 1) and augment antigen (signal 2)-induced allergic airway inflammation...
  28. ncbi request reprint Signaling molecules as therapeutic targets in allergic diseases
    Magdalena M Gorska
    Division of Allergy and Immunology, National Jewish Medical and Research Center and University of Colorado Health Sciences Center, Denver, CO, USA
    J Allergy Clin Immunol 112:241-50; quiz 251. 2003
    ..The purpose of this review was to provide a theoretical classification of signaling molecules based on their function and to analyze various strategies for developing effective signaling inhibitors for allergic diseases...
  29. ncbi request reprint Identification of UNC119 as a novel activator of SRC-type tyrosine kinases
    Osman Cen
    Division of Allergy and Immunology, NIAID, National Institutes of Health Asthma and Allergic Diseases Research Center, Bethesda, Maryland 20892, USA
    J Biol Chem 278:8837-45. 2003
    ..Inhibition of Unc119 down-regulates eosinophil survival. To our knowledge Unc119 is the first receptor-associated activator of Src family tyrosine kinases...
  30. ncbi request reprint The signaling mechanism of eosinophil activation
    Magdalena M Gorska
    Division of Allergy and Immunology, National Jewish Medical and Research Center, 1400 Jackson Street, Denver, CO 80206, USA
    Expert Rev Clin Immunol 1:247-56. 2005
    ..The biologic consequences of many of these signaling pathways are also discussed...
  31. ncbi request reprint Chronic urticaria sera increase basophil CD203c expression
    Karen M Yasnowsky
    Department of Medicine, Division of Allergy and Clinical Immunology, University of Colorado Health Sciences Center and the National Jewish Medical and Research Center, Denver, CO 80206, USA
    J Allergy Clin Immunol 117:1430-4. 2006
    ..CD203c is a basophil activation marker known to be upregulated by cross-linking of the FcepsilonRIalpha receptor and may serve as a useful marker to identify these patients...