Research Topics
Genomes and Genes | Luis DiazSummaryAffiliation: University of North Carolina Country: USA Publications
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Publications
End of the century overview of skin blistersL A Diaz
Department of Dermatology, Medical College of Wisconsin, Milwaukee, USA
Arch Dermatol 136:106-12. 2000..Recent advances have uncovered the relevance of the keratinocyte cytoskeleton, the desmosome, the hemidesmosome, and extracellular matrix proteins in blister formation. A pathogenetic classification of blistering diseases is presented...- Anti-desmoglein-1 antibodies in onchocerciasis, leishmaniasis and Chagas disease suggest a possible etiological link to Fogo selvagemLuis A Diaz
Department of Dermatology, University of North Carolina at Chapel Hill, North Carolina, USA
J Invest Dermatol 123:1045-51. 2004..In persons with the known HLA susceptibility alleles and living in endemic areas, a response to the EC1-2 domains may subsequently develop by epitope spreading with associated clinical signs of FS... - The IgM anti-desmoglein 1 response distinguishes Brazilian pemphigus foliaceus (fogo selvagem) from other forms of pemphigusLuis A Diaz
Department of Dermatology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA
J Invest Dermatol 128:667-75. 2008..Recurrent environmental antigenic exposure may lead to IgM and IgG responses that trigger FS. JID JOURNAL CLUB ARTICLE: For questions, answers, and open discussion about this article please go to http://network.nature.com/group/jidclub... - Complete FcRn dependence for intravenous Ig therapy in autoimmune skin blistering diseasesNing Li
Department of Dermatology, University of North Carolina at Chapel Hill, North Carolina 27599, USA
J Clin Invest 115:3440-50. 2005..These data demonstrate that the therapeutic efficacy of HDIG treatment in the pemphigus and pemphigoid models is dependent on FcRn. Thus, FcRn is a promising therapeutic target for treating such IgG-mediated autoimmune diseases... - Macrophages, but not T and B lymphocytes, are critical for subepidermal blister formation in experimental bullous pemphigoid: macrophage-mediated neutrophil infiltration depends on mast cell activationRuoyan Chen
Department of Dermatology, University of North Carolina, Chapel Hill, NC 27599, USA
J Immunol 169:3987-92. 2002..MCs play a major role in neutrophil recruitment into the dermis. Furthermore, Mphi-mediated neutrophil infiltration depends on MC activation/degranulation... - Experimental models for the autoimmune and inflammatory blistering disease, Bullous pemphigoidLisa Leighty
Department of Dermatology, University of North Carolina School of Medicine, 3100 Thurston Bowles, Chapel Hill, NC 27599, USA
Arch Dermatol Res 299:417-22. 2007..The development of two novel humanized mouse models for the first time has enabled study of disease mechanisms caused by BP autoantibodies, and presents an ideal in vivo system to test novel therapeutic strategies for disease management... - Role of FcRs in animal model of autoimmune bullous pemphigoidMinglang Zhao
Department of Dermatology, University of North Carolina School of Medicine, Chapel Hill 27599, USA
J Immunol 177:3398-405. 2006..Results from this study establish that Fc gammaRIII plays a critical role in the activation of infiltrating neutrophils and the subsequent blistering in experimental BP... - A subset of pemphigus foliaceus patients exhibits pathogenic autoantibodies against both desmoglein-1 and desmoglein-3Luis A Arteaga
Department of Dermatology, University of North Carolina at Chapel Hill, 27599, USA
J Invest Dermatol 118:806-11. 2002..These results suggest that a subset of patients with pemphigus foliaceus and fogo selvagem have antibodies to desmoglein-3 that may be involved in the pathogenesis of their cutaneous disease... - Biphasic activation of p38MAPK suggests that apoptosis is a downstream event in pemphigus acantholysisHua En Lee
Department of Dermatology, The University of North Carolina School of Medicine, Chapel Hill, NC 27599 7287, USA
J Biol Chem 284:12524-32. 2009..Furthermore, these observations suggest that the earlier peak of p38MAPK activation is part of the mechanism leading to acantholysis, whereas the later peak of p38MAPK and apoptosis may not be essential for acantholysis... - Role of different pathways of the complement cascade in experimental bullous pemphigoidKelly C Nelson
Department of Dermatology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA
J Clin Invest 116:2892-900. 2006..These findings provide the first direct evidence to our knowledge that complement activation via the classical and alternative pathways is crucial in subepidermal blister formation in experimental BP... - Subepidermal blistering induced by human autoantibodies to BP180 requires innate immune players in a humanized bullous pemphigoid mouse modelZhi Liu
Department of Dermatology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
J Autoimmun 31:331-8. 2008..The NC16A+/+ mice pretreated with mast cell activation blocker or depleted of complement or neutrophils become resistant to BP. These findings suggest that the humoral response in BP critically depends on innate immune system players... - Inhibition of pemphigus vulgaris by targeting of the CD40-CD154 co-stimulatory pathway: a step toward antigen-specific therapy?Zhi Liu
Department of Dermatology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA
J Invest Dermatol 126:11-3. 2006..Thus, blockade of this ligand-receptor interaction can prevent the development of antibody-mediated autoimmune diseases through different mechanisms... - Prevalence of anti-desmoglein-3 antibodies in endemic regions of Fogo selvagem in BrazilJulio Hilario-Vargas
Department of Dermatology, University of North Carolina at Chapel Hill, 27599, USA
J Invest Dermatol 126:2044-8. 2006.... - The role of intramolecular epitope spreading in the pathogenesis of endemic pemphigus foliaceus (fogo selvagem)Ning Li
Department of Dermatology, University of North Carolina at Chapel Hill, 3100 Thurston Building, CB 7287 Chapel Hill, NC 27599, USA
J Exp Med 197:1501-10. 2003..Moreover, intramolecular epitope spreading may also modulate remissions and relapses of FS... - Pemphigus antibody induced phosphorylation of keratinocyte proteinsDavid S Rubenstein
Department of Dermatology, University of North Carolina Chapel Hill, Chapel Hill, NC 27599 7287, USA
Autoimmunity 39:577-86. 2006..Activation of p38 mitogen activated protein kinase may have a critical role in the acantholytic mechanism as inhibitors of p38MAPK block the ability of pemphigus IgG to induce blistering in pemphigus animal models... - Involvement of the apoptotic mechanism in pemphigus foliaceus autoimmune injury of the skinNing Li
Department of Dermatology, University of North Carolina, Chapel Hill, NC 27599, USA
J Immunol 182:711-7. 2009..Collectively, these findings show that biochemical events of apoptosis are provoked in the epidermis of mice injected with PF autoantibodies. Caspase activation may contribute to acantholytic blister formation in PF... - Autoantibodies in the autoimmune disease pemphigus foliaceus induce blistering via p38 mitogen-activated protein kinase-dependent signaling in the skinPaula Berkowitz
Department of Dermatology, The University of North Carolina School of Medicine, Chapel Hill, NC 27599 7287, USA
Am J Pathol 173:1628-36. 2008..Inhibition of p38 MAPK may be an effective strategy for the treatment of PF... - Antigen selection of anti-DSG1 autoantibodies during and before the onset of endemic pemphigus foliaceusYe Qian
Department of Dermatology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA
J Invest Dermatol 129:2823-34. 2009..We conclude that the anti-DSG1 response in FS is antigen driven and that selection for mutant anti-DSG1 B cells begins well before the onset of disease... - The Thomsen-Friedenreich antigen-binding lectin jacalin interacts with desmoglein-1 and abrogates the pathogenicity of pemphigus foliaceus autoantibodies in vivoNing Li
Department of Dermatology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA
J Invest Dermatol 130:2773-80. 2010..TF-specific binding ligands may have a potential therapeutic value for PF... - Differential roles for beta2 integrins in experimental autoimmune bullous pemphigoidZhi Liu
Department of Dermatology, University of North Carolina, Chapel Hill, NC 27599, USA
Blood 107:1063-9. 2006..These data suggest that beta2 integrins play differential roles in experimental BP: LFA-1 is required for neutrophil recruitment, while Mac-1 mediates late neutrophil accumulation and apoptosis of infiltrating neutrophils... - Synergy between a plasminogen cascade and MMP-9 in autoimmune diseaseZhi Liu
Department of Dermatology, University of North Carolina, Chapel Hill, North Carolina 27599, USA
J Clin Invest 115:879-87. 2005..Thus, the Plg/plasmin system is epistatic to MMP-9 activation and subsequent dermal-epidermal separation in BP... - Complement and cutaneous autoimmune blistering diseasesElizabeth Lessey
Department of Dermatology, University of North Carolina, Chapel Hill, NC 27599, USA
Immunol Res 41:223-32. 2008.... - p38MAPK signaling and desmoglein-3 internalization are linked events in pemphigus acantholysisPuneet S Jolly
Department of Dermatology, University of North Carolina, Chapel Hill, North Carolina 27599 7287, USA
J Biol Chem 285:8936-41. 2010..These data suggest that p38MAPK is capable of regulating PV IgG-mediated DSG3 internalization and that previously isolated mechanistic observations may be linked to a common pathway by which pemphigus autoantibodies lead to acantholysis... - Advances in pemphigus and its endemic pemphigus foliaceus (Fogo Selvagem) phenotype: a paradigm of human autoimmunityDonna A Culton
Department of Dermatology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
J Autoimmun 31:311-24. 2008.... - E-cadherin is an additional immunological target for pemphigus autoantibodiesFlor Evangelista
Department of Dermatology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA
J Invest Dermatol 128:1710-8. 2008..The functional relevance of these anti-E-cadherin IgG autoantibodies detected in these pemphigus sera remains to be defined... - Pemphigus foliaceusDavid Dasher
Department of Dermatology, University of North Carolina Chapel Hill School of Medicine, Chapel Hill, NC 27599, USA
Curr Dir Autoimmun 10:182-94. 2008..The study of the pathogenesis of PF and FS provides a unique opportunity to uncover insights that may contribute to our greater understanding of autoimmunity... - Dissecting the anti-desmoglein autoreactive B cell repertoire in pemphigus vulgaris patientsYe Qian
Department of Dermatology, University of North Carolina, Chapel Hill, NC 27599, USA
J Immunol 178:5982-90. 2007..We conclude that the potentially pathogenic IgG anti-Dsg response is restricted in V(H) use, is somatically mutated, and is Ag selected... - p38MAPK inhibition prevents disease in pemphigus vulgaris micePaula Berkowitz
Department of Dermatology and Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC 27599-7287, USA
Proc Natl Acad Sci U S A 103:12855-60. 2006..We now report that p38MAPK inhibitors prevented PV blistering disease in vivo. Targeting the end-organ by inhibiting keratinocyte desmosome signaling may be effective for treating desmosome autoimmune blistering disorders... - Development of an IgG4-based predictor of endemic pemphigus foliaceus (fogo selvagem)Bahjat F Qaqish
Department of Biostatisitcs, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA
J Invest Dermatol 129:110-8. 2009..Identifying individuals during preclinical FS will enhance our ability to identify the etiological agent(s) triggering FS... - Desmosome signaling. Inhibition of p38MAPK prevents pemphigus vulgaris IgG-induced cytoskeleton reorganizationPaula Berkowitz
Department of Dermatology, University of North Carolina-Chapel Hill School of Medicine, 27599, USA
J Biol Chem 280:23778-84. 2005..Targeting desmosome signaling via inhibition of p38MAPK and HSP27 phosphorylation may provide novel treatments for PV and other desmosome-associated blistering diseases... - Humoral autoimmunity in pemphigusErin K Pias
Department of Dermatology, University of North Carolina at Chapel Hill, 3100 Thurston Building, Chapel Hill, NC 27599, USA
Autoimmunity 37:283-6. 2004 - T cell receptor Beta chain gene usage in endemic pemphigus foliaceus (fogo selvagem)Achim K Moesta
Department of Dermatology, Weill Medical College of Cornell University, New York, NY 10021, USA
J Invest Dermatol 119:377-83. 2002..Furthermore, T cell receptor beta variable region and beta joining usage did not appear to be random, but oligoclonal in nature, with some preference shown for T cell receptor beta variable region 5S1 and T cell receptor BJ2S5... - Pemphigus foliaceus with neutrophilic spongiosis evolving to an atypical pemphigus phenotypeTatiana Villas Boas Gabbi
Department of Dermatology, , , Brazil
J Am Acad Dermatol 51:1012-3. 2004..Interestingly, his autoantibody profile, tested by immunofluorescence, immunoblotting, enzyme-linked immunosorbent assay, and immunoprecipitation revealed exclusive IgG anti-desmoglein 1 antibodies in all phases of the disease... - Pharmacologic and toxicologic evaluation of C. novyi-NT sporesLuis A Diaz
Howard Hughes Medical Institute, The Johns Hopkins School of Medicine, Baltimore, MD 21231, USA
Toxicol Sci 88:562-75. 2005..However, there was no laboratory or histopathologic evidence of sepsis, and the toxicity could be effectively controlled by simple hydration... - Environmental risk factors in endemic pemphigus foliaceus (fogo selvagem)Valeria Aoki
Department of Dermatology, University of Sao Paulo, Sao Paulo, Brazil
J Investig Dermatol Symp Proc 9:34-40. 2004..These findings suggest that the environmental antigen(s) triggering the autoimmune response in FS may be linked to exposure to hematophagous insects... - Endemic pemphigus vulgarisRosicler Rocha Alvarez
Department of Dermatology, Universidade Federal de Brasilia, Brasilia, Distrito Federal
Arch Dermatol 143:895-9. 2007..Our objective was to characterize antidesmoglein 3 and antidesmoglein 1 autoantibody profiles in these unique patients who reside in Goiânia and Brasilia, Brazil, known endemic regions of fogo selvagem... - Induction of p38MAPK and HSP27 phosphorylation in pemphigus patient skinPaula Berkowitz
J Invest Dermatol 128:738-40. 2008 - IgM-mediated epidermolysis bullosa acquisitaJeffrey M Suchniak
Arch Dermatol 138:1385-6. 2002 - Xenogeneic cells and superantigen induce human T-cell activation in the absence of T-cell recognition of xenoantigenLuis A Diaz
Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, 48109, USA
J Lab Clin Med 142:149-57. 2003..After such interactions T-cells can develop secondary responses in autologous interactions based on retention of minute amounts of SAg. Such interactions may have important implications for xenotransplantation... - Immunopathological mechanisms of acantholysis in pemphigus vulgaris: an explanation by ultrastructural observationsZhi Liu
J Invest Dermatol 122:XIII-XIV. 2004 - Mutant PIK3CA promotes cell growth and invasion of human cancer cellsYardena Samuels
The Sidney Kimmel Comprehensive Cancer Center and The Howard Hughes Medical Institute, The Johns Hopkins University Medical Institutions, Baltimore, MD 21231, USA
Cancer Cell 7:561-73. 2005..Treatment with the PI3K inhibitor LY294002 abrogated PIK3CA signaling and preferentially inhibited growth of PIK3CA mutant cells. These data have important implications for therapy of cancers harboring PIK3CA alterations... - Bacteriolytic therapy can generate a potent immune response against experimental tumorsNishant Agrawal
Howard Hughes Medical Institute, Johns Hopkins Medical Institutions, Baltimore, MD 21231, USA
Proc Natl Acad Sci U S A 101:15172-7. 2004..Similar effects were observed in rabbits with intrahepatic tumors. It was particularly notable that the induced immune response, when combined with the bacteriolytic effects of C. novyi-NT, could eradicate large established tumors... - The genome and transcriptomes of the anti-tumor agent Clostridium novyi-NTChetan Bettegowda
The Howard Hughes Medical Institute, The Ludwig Center for Cancer Genetics and Therapeutics, The Sidney Kimmel Comprehensive Cancer Center, Department of Pharmacology and Molecular Sciences, Johns Hopkins Medical Institutions, Baltimore, Maryland 21231, USA
Nat Biotechnol 24:1573-80. 2006..Through this analysis, we found that C. novyi-NT spores contained mRNA and that the spore transcripts were distinct from those in vegetative forms of the bacterium... - Serial assessment of human tumor burdens in mice by the analysis of circulating DNACarlo Rago
The Ludwig Center for Cancer Genetics and Therapeutics and The Howard Hughes Medical Institute, Baltimore, Maryland, USA
Cancer Res 67:9364-70. 2007..A marked, transient spike in circulating human tumor DNA occurred immediately after cytotoxic therapy or surgery. This simple assay may find broad utility in target validation studies and preclinical drug development programs... - Rituximab and pemphigus--a therapeutic advanceLuis A Diaz
N Engl J Med 357:605-7. 2007 - A bacterial protein enhances the release and efficacy of liposomal cancer drugsIan Cheong
Howard Hughes Medical Institute and the Ludwig Center for Cancer Genetics and Therapeutics, Johns Hopkins Kimmel Comprehensive Cancer Center, Baltimore, MD 21231, USA
Science 314:1308-11. 2006..This protein could potentially be incorporated into diverse experimental approaches for the specific delivery of chemotherapeutic agents to tumors...
Research Grants
- TRAINING GRANT IN DERMATOLOGICAL RESEARCHLuis Diaz; Fiscal Year: 2006..This competitive grant application requests funding to support the training at the UNC Dermatology Department of the next generation of dermatological investigators. ..
- ETIOLOGY AND PATHOGENESIS OF PEMPHIGUSLuis Diaz; Fiscal Year: 2006..It is likely that characteristics of the mechanism of autoimmunity for FS will be shared with other human autoimmune diseases and what we learn from ES will be applicable to the study of human autoimmunity. ..
- PEMPHIGUS AND PEMPHIGOIDLuis Diaz; Fiscal Year: 2007..Finally, we will generate human anti-idiotypic antibodies by phage display technology and attempt to block binding of PV or PF/FS autoantibodies to their target epidermal antigens, thus preventing disease. ..
- ETIOLOGY AND PATHOGENESIS OF PEMPHIGUSLuis A Diaz; Fiscal Year: 2010..At the completion of this application we will have a better understanding of other human autoimmune diseases like lupus erythematosus, rheumatoid arthritis, thyroiditis, and others. ..
- PEMPHIGUS AND PEMPHIGOIDLuis Diaz; Fiscal Year: 2005..Similar studies will be performed with anti-dsg3 autoantibodies in PV. These studies may lead to new therapies for these serious cutaneous autoimmune diseases. ..
- ETIOLOGY AND PATHOGENESIS OF PEMPHIGUSLuis Diaz; Fiscal Year: 2001..Information obtained from these studies should be relevant in understanding the onset and development of FS and other human autoimmune diseases. ..
- PEMPHIGUS AND PEMPHIGOIDLuis A Diaz; Fiscal Year: 2010..Finally, we will generate human anti-idiotypic antibodies by phage display technology and attempt to block binding of PV or PF/FS autoantibodies to their target epidermal antigens, thus preventing disease. ..