Research Topics
Genomes and Genes | Harold A ChapmanSummaryAffiliation: University of California Country: USA Publications
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Publications
Role for cathepsin F in invariant chain processing and major histocompatibility complex class II peptide loading by macrophagesG P Shi
Department of Medicine, Brigham and Women s Hospital and Harvard Medical School, Harvard Medical School, Boston, Massachusetts 02115, USA
J Exp Med 191:1177-86. 2000..These experiments show that cathepsin F, in a subset of antigen presenting cells (APCs), can efficiently degrade Ii. Different APCs can thus use distinct proteases to mediate MHC class II maturation and peptide loading...
Protease crosstalk with integrins: the urokinase receptor paradigmH A Chapman
Pulmonary and Critical Care Division, University of California at San Francisco, 94143 0130, USA
Thromb Haemost 86:124-9. 2001..Signals derived from integrin/uPAR complexes promote the function of other integrins. Thus the urokinase/plasmin system coordinates with integrins to regulate cell: matrix interactions...
Disorders of lung matrix remodelingHarold A Chapman
Department of Medicine and Cardiovascular Research Institute, University of California at San Francisco, San Francisco, California 94143 0130, USA
J Clin Invest 113:148-57. 2004..This review examines the common pathogenetic features of these disorders in light of recent observations in both humans and animal models of disease, which reveal important pathways of lung matrix remodeling...
Urokinase receptors are required for alpha 5 beta 1 integrin-mediated signaling in tumor cellsYing Wei
Pulmonary and Critical Care Division, Department of Medicine and Cardiovascular Research Institute, University of California, San Francisco, California 94143 0111, USA
J Biol Chem 282:3929-39. 2007..Thus urokinase receptor binding to alpha5beta1 is required for maximal responses to fibronectin and tumor cell invasion, and this operates through an enhanced Src/Rac/ERK signaling pathway...
Epithelial cell alpha3beta1 integrin links beta-catenin and Smad signaling to promote myofibroblast formation and pulmonary fibrosisKevin K Kim
Pulmonary and Critical Care Division, Department of Medicine, and Cardiovascular Research Institute, UCSF, San Francisco, CA 94143, USA
J Clin Invest 119:213-24. 2009..These findings demonstrate epithelial integrin-dependent profibrotic crosstalk between beta-catenin and Smad signaling and support the hypothesis that EMT is an important contributor to pathologic fibrosis...
Epithelial responses to lung injury: role of the extracellular matrixHarold A Chapman
Pulmonary and Critical Care Division, University of California at San Francisco, 513 Parnassus Avenue, San Francisco, CA 94143 0130, USA
Proc Am Thorac Soc 9:89-95. 2012..Elucidation of specific inhibitors of EMT should further test the question of whether the process is important to fibrosis in vivo and a viable therapeutic target...
Integrin alpha3beta1-dependent beta-catenin phosphorylation links epithelial Smad signaling to cell contactsYoung Kim
Pulmonary and Critical Care Division, Department of Medicine, and Cardiovascular Research Institute, University of California, San Francisco, San Francisco, CA 94143, USA
J Cell Biol 184:309-22. 2009..These findings demonstrate that alpha3beta1 coordinates cross talk between beta-catenin and Smad signaling pathways as a function of extracellular contact cues and thereby regulates responses to TGF-beta1 activation...
Alveolar epithelial cell mesenchymal transition develops in vivo during pulmonary fibrosis and is regulated by the extracellular matrixKevin K Kim
Department of Medicine and Cardiovascular Research Institute, University of California, San Francisco, 94143, USA
Proc Natl Acad Sci U S A 103:13180-5. 2006..These data reveal alveolar epithelial cells as progenitors for fibroblasts in vivo and implicate the provisional extracellular matrix as a key regulator of epithelial transdifferentiation during fibrogenesis...
Axin pathway activity regulates in vivo pY654-β-catenin accumulation and pulmonary fibrosisArnau Ulsamer
Pulmonary and Critical Care Division, Department of Medicine and Cardiovascular Research Institute, University of California, San Francisco, California 94143, USA
J Biol Chem 287:5164-72. 2012....
Signaling through urokinase and urokinase receptor in lung cancer cells requires interactions with beta1 integrinsChi Hui Tang
Pulmonary and Critical Care Division, Department of Medicine, Cardiovascular Research Institute, University of California San Francisco, San Francisco, CA 94143, USA
J Cell Sci 121:3747-56. 2008..Taken together, the results indicate that uPAR-beta1-integrin interactions are essential to signals induced by integrin matrix ligands or uPA that support lung cancer cell invasion in vitro and progression in vivo...
Integrin α6β4 identifies an adult distal lung epithelial population with regenerative potential in miceHarold A Chapman
Department of Medicine, Cardiovascular Research Institute, and Lung Biology Center, UCSF, San Francisco, California 94143, USA
J Clin Invest 121:2855-62. 2011....
Regulation of alpha5beta1 integrin conformation and function by urokinase receptor bindingYing Wei
Department of Medicine and Pulmonary and Critical Care Division, University of California, San Francisco, San Francisco, CA 94143, USA
J Cell Biol 168:501-11. 2005..Direct binding and regulation of alpha5beta1 by uPAR implies a modified "bent" integrin conformation can function in an alternative activation state with this and possibly other cis-acting membrane ligands...
Distinct ligand binding sites in integrin alpha3beta1 regulate matrix adhesion and cell-cell contactFeng Zhang
Pulmonary and Critical Care Division, University of California San Francisco, 513 Parnassus Ave, San Francisco, CA 94143-0130, USA
J Cell Biol 163:177-88. 2003..These studies reveal an integrin- and Src-dependent pathway for SLUG expression and mesenchymal transition...
Alveolar epithelial cells express mesenchymal proteins in patients with idiopathic pulmonary fibrosisCecilia Marmai
Department of Medicine and Cardiovascular Research Institute, University of California, San Francisco, California 94143 0111, USA
Am J Physiol Lung Cell Mol Physiol 301:L71-8. 2011..These data suggest that alveolar type II cells can acquire features of mesenchymal cells in IPF lungs and that TGF-β can mediate this process...
Endosomal proteases in antigen presentationHarold A Chapman
Department of Medicine and the Cardiovascular Research Institute, University of California, San Francisco, CA 94143, USA
Curr Opin Immunol 18:78-84. 2006..Repeated implication of cathepsins in processing medically important antigens holds promise for therapeutic manipulation of proteases in diseases in which there is disordered adaptive immunity...
Epithelial-mesenchymal interactions in pulmonary fibrosisHarold A Chapman
Department of Medicine, Cardiovascular Research Institute, University of California, San Francisco, 94143, USA
Annu Rev Physiol 73:413-35. 2011..Understanding specific signaling mechanisms driving the mesenchymal response to TGFβ1 may reveal therapeutics to attenuate fibrogenesis yet preserve the important homeostatic functions of TGFβ1...
Murine cathepsin F deficiency causes neuronal lipofuscinosis and late-onset neurological diseaseChi Hui Tang
Department of Medicine, and the Cardiovascular Research Institute, University of California, San Francisco, Box 0111, San Francisco, CA 94143, USA
Mol Cell Biol 26:2309-16. 2006..cat F is the only cysteine cathepsin whose inactivation alone causes a lysosomal storage defect and progressive neurological features in mice. The late onset suggests that this gene may be a candidate for adult-onset NCL...
Cathepsins L and S are not required for activation of dipeptidyl peptidase I (cathepsin C) in miceJon Mallen-St Clair
Department of Medicine and Cardiovascular Research Institute, University of California, San Francisco, CA 94143 0111, USA
Biol Chem 387:1143-6. 2006..These results show that neither cathepsin L nor S is required for activation of DPPI and suggest that one or more additional proteases is responsible...
Suppression of tumor invasion and metastasis by concurrent inhibition of c-Met and VEGF signaling in pancreatic neuroendocrine tumorsBarbara Sennino
Comprehensive Cancer Center, Department of Anatomy, University of California San Francisco UCSF, San Francisco, CA 94143 0452, USA
Cancer Discov 2:270-87. 2012..The results show that simultaneous inhibition of c-Met and VEGF signaling not only slows tumor growth but also reduces invasion and metastasis...
Urokinase receptor and integrin interactionsMatthias C Kugler
Department of Medicine, Pulmonary and Critical Care Division, and CVRI University of California, San Francisco, 94143, USA
Curr Pharm Des 9:1565-74. 2003..Together these observations support the idea that uPAR:integrin interactions may be a focal point of intervention in pathobiology where integrin function is crucial, such as tumor metastasis...
Cathepsin S is not crucial to TSHR processing and presentation in a murine model of Graves' diseaseMrinalini Kala
Department of Medicine and Cardiovascular Research Institute, University of California, San Francisco, 93143, USA
Immunology 116:532-40. 2005..Contrasting findings among organ-specific murine autoimmune models imply that potential uses of Cat S inhibitors to ameliorate autoimmunity must be determined empirically...
Functional relevance of urinary-type plasminogen activator receptor-alpha3beta1 integrin association in proteinase regulatory pathwaysSupurna Ghosh
Department of Cell and Molecular Biology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USA
J Biol Chem 281:13021-9. 2006....
Role of cathepsin S-dependent epithelial cell apoptosis in IFN-gamma-induced alveolar remodeling and pulmonary emphysemaTao Zheng
Department of Internal Medicine, Yale University School of Medicine, Section of Pulmonary and Critical Care Medicine, New Haven, CT 06520, USA
J Immunol 174:8106-15. 2005..They also link inflammation, protease/antiprotease alterations, and protease-dependent apoptosis in the pathogenesis of Th1/Tc1 cytokine-induced tissue remodeling and destructive responses...
Adenovirally mediated expression of urokinase receptor binding site on integrin alpha-chain blocks adhesion and migration of human lung fibroblastsSha Zhu
Department of Medicine, Division of Pulmonary and Critical Care Medicine, University of Alabama, Birmingham AL 35294, USA
Chest 121:34S-35S. 2002
Endothelin-1 as initiator of epithelial-mesenchymal transition: potential new role for endothelin-1 during pulmonary fibrosisKevin K Kim
Am J Respir Cell Mol Biol 37:1-2. 2007
Random peptide bacteriophage display as a probe for urokinase receptor ligandsSusan Fong
Chiron Corporation, Emeryville, CA 94608, USA
Biol Chem 383:149-58. 2002....
Cutting edge: Deficiency of macrophage migration inhibitory factor impairs murine airway allergic responsesBing Wang
Department of Medicine, Brigham and Women s Hospital and Harvard Medical School, 77th Avenue Louis Pasteur, Boston, MA 02115, USA
J Immunol 177:5779-84. 2006....
Cathepsin S is required for murine autoimmune myasthenia gravis pathogenesisHuan Yang
Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555 1070, USA
J Immunol 174:1729-37. 2005..Because Cat S null mice are not severely immunocompromised, Cat S inhibitors could be tested for their therapeutic potential in EAMG...
Cystatin C deficiency increases elastic lamina degradation and aortic dilatation in apolipoprotein E-null miceGalina K Sukhova
Donald W Reynolds Cardiovascular Clinical Research Center, Department of Medicine, Brigham and Women s Hospital Harvard Medical School, Boston, Mass, USA
Circ Res 96:368-75. 2005..These findings demonstrate directly the importance of cysteine protease/protease inhibitor balance in dysregulated arterial integrity and remodeling during experimental atherogenesis...
The transforming growth factor-beta1 (TGFB1) gene is associated with chronic obstructive pulmonary disease (COPD)Juan C Celedon
Channing Laboratory, Division of Pulmonary and Critical Care Medicine, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
Hum Mol Genet 13:1649-56. 2004..We hypothesize that genetic variants in or near the TGFB1 gene influence the pathogenesis of COPD among cigarette smokers...
The SERPINE2 gene is associated with chronic obstructive pulmonary diseaseDawn L DeMeo
Channing Laboratory, Department of Medicine, Brigham and Women s Hospital, Boston, MA 02115, USA
Am J Hum Genet 78:253-64. 2006....
Future research directions in idiopathic pulmonary fibrosis: summary of a National Heart, Lung, and Blood Institute working groupRonald G Crystal
Division of Pulmonary and Critical Care Medicine, Weill Medical College of Cornell University, New York, New York, USA
Am J Respir Crit Care Med 166:236-46. 2002....
The SERPINE2 gene is associated with chronic obstructive pulmonary diseaseDawn DeMeo
Channing Laboratory, Harvard Medical School, 181 Longwood Avenue, Boston, MA 02115, USA
Proc Am Thorac Soc 3:502. 2006
