Please join us for the Philadelphia Science Forum series talk, 5:30-7:30pm Wednesday(March 3) at CRB Room 302.
Title: Seeking therapy for autoimmune diseases: from library screening to patient treatment
Speaker: Dr. Xuming Mao (Department of Dermatology, UPenn)
Abstract: Autoimmune diseases occur when an overactive immune response attacks tissues or cells normally present in the human body. Pemphigus represents one of the autoimmune disorders that target only the skin and mucous membranes. It is a potentially fatal blistering disease characterized by autoantibodies against desmoglein (Dsg) cell adhesion proteins. To study the role of autoantibodies in pathogenesis and seek new specific treatments, we isolated lymphocytes from patients with pemphigus, followed by mRNAs to establish a cDNA expression library. Using antibody phage display, we have isolated repertoires of human anti-Dsg mAbs as single-chain variable-region fragments (scFvs) from a patient with active mucocutaneous pemphigus vulgaris. Injection of these pathogenic but not the nonpathogenic antibodies reproduced blisters in animal models or in organ-cultured human skin. In vitro studies showed mAb causes rapid internalization of Dsg during assembly in skin epidermal cells. Furthermore, we found the pathogenic antibodies triggered activation of certain signaling pathways that may contribute to antibody-mediated pathogenecity. Our preliminary results have demonstrated that interference of antibody binding or subsequent activation of cell signaling will help us to identify targeted therapy of pemphigus in the future.
Snack and beverage will be served.
Title: Seeking therapy for autoimmune diseases: from library screening to patient treatment
Speaker: Dr. Xuming Mao (Department of Dermatology, UPenn)
Abstract: Autoimmune diseases occur when an overactive immune response attacks tissues or cells normally present in the human body. Pemphigus represents one of the autoimmune disorders that target only the skin and mucous membranes. It is a potentially fatal blistering disease characterized by autoantibodies against desmoglein (Dsg) cell adhesion proteins. To study the role of autoantibodies in pathogenesis and seek new specific treatments, we isolated lymphocytes from patients with pemphigus, followed by mRNAs to establish a cDNA expression library. Using antibody phage display, we have isolated repertoires of human anti-Dsg mAbs as single-chain variable-region fragments (scFvs) from a patient with active mucocutaneous pemphigus vulgaris. Injection of these pathogenic but not the nonpathogenic antibodies reproduced blisters in animal models or in organ-cultured human skin. In vitro studies showed mAb causes rapid internalization of Dsg during assembly in skin epidermal cells. Furthermore, we found the pathogenic antibodies triggered activation of certain signaling pathways that may contribute to antibody-mediated pathogenecity. Our preliminary results have demonstrated that interference of antibody binding or subsequent activation of cell signaling will help us to identify targeted therapy of pemphigus in the future.
Snack and beverage will be served.
