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Aimee S. Payne, M.D., Ph.D.
Assistant Professor

Clinical:
2 Rhoads, 3600 Spruce Street

Philadelphia, PA 19104
Tel: 215-662-2737; Fax: 215-662-4131

Office:
217A Clinical Research Building, 415 Curie Blvd.
Philadelphia, PA 19104
Tel: 215-746-4488; Fax: 215-573-7173
                              Email: paynea@mail.med.upenn.edu

 
     
 

Education
1993            B.S.                   Stanford University
2001            M.D./Ph.D.          Washington University School of Medicine
2001-02       Internship           Internal Medicine, Pennsylvania Hospital

2002-05       Residency           Dermatology, University of Pennsylvania

Clinical Specialties
General dermatology; autoimmune blistering skin diseases

Research Areas of Interest:
Pemphigus, cell adhesion, autoimmunity

Research Summary:
Our research centers on mechanisms of pathophysiology in pemphigus, a potentially fatal autoimmune blistering disease of the skin and mucous membranes caused by antibodies against desmosomal cell adhesion molecules known as desmogleins. However, not all antibodies that react with desmogleins cause disease, as patients in remission and unaffected relatives often demonstrate serum anti-desmoglein antibodies. Ultimately, a better understanding of disease pathogenesis and more specific treatments will require investigation of how pathogenic autoantibodies develop within patients and whether pathogenic antibody idiotypes are shared among patients.

Using phage display, we have isolated monoclonal anti-desmoglein antibodies from a patient with active mucocutaneous pemphigus vulgaris (PV). Library analysis suggests that a limited number of antibody genes encode the human PV autoantibody repertoire, with different genes for pathogenic and non-pathogenic antibodies. Targeting of the heavy chain variable region genes identified in the first PV patient library blocked the pathogenic activity of the patient's serum against cultured human keratinocytes, indicating that more specific and potentially safer antibody-targeted therapies for pemphigus may be feasible. We are currently characterizing additional PV libraries to evaluate for shared autoantibody gene usage among PV patients.

Another major question in pemphigus pathophysiology is how anti-desmoglein antibodies result in acantholysis, or cell dissociation. Using our PV monoclonal antibodies, we are studying the effects of pathogenic and non-pathogenic anti-desmoglein antibodies on the kinetics of desmoglein turnover in human keratinocytes. These studies aim to elucidate pathways of desmosome assembly and disassembly, with relevance to disease pathophysiology.

Lab Members:

    Preety Sharma, Ph.D. - Postdoctoral Fellow

    Eun Jung Choi, M.S. - Research Assistant

    Xuming Mao, M.D., Ph.D. - Postdoctoral Fellow

Selected Publications

    Payne AS, Hanakawa Y, Amagai M, and Stanley JR. (2004)     Desmosomes and disease: pemphigus and bullous impetigo.
    Curr. Opin. Cell Biol., 16, 536-543.

    Payne AS, Ishii K, Kacir S, Lin C, Li H, Hanakawa Y, Tsunoda K,
    Amagai M, Stanley JR, and Siegel DL. (2005) Genetic and functional     characterization of human pemphigus vulgaris monoclonal     autoantibodies isolated by phage display.
    J. Clin. Invest., 115, 888-899.

    Payne AS, Yan AC, Ilyas E, Li W, Seykora JT, Young TL, Pawel BR,     Honig PJ, Camacho J, Imaizumi S, Heymann WR, and Schnur RE. (2005)     Two novel TP63 mutations associated with the ankyloblepharon,     ectodermal defects, and cleft lip and palate syndrome: a skin fragility     phenotype. Arch. Dermatol., 141, 1567-1573.

    Payne AS, James WD, and Weiss RB. (2006) Dermatologic toxicity of     chemotherapeutic agents. Semin. Oncol., 33, 86-97.

    Payne AS, Siegel DL, and Stanley JR. (2007) Targeting pemphigus     autoantibodies through their heavy chain variable region genes.
    J.Invest.Dermatol., 127, 1681-1691.

    Sharma P, Mao X, and Payne AS. (2007) Beyond steric hindrance: the     role of adhesion signaling pathways in the pathogenesis of pemphigus.
    J. Dermatol. Sci., 48: 1-14.

Links of Interest

     Cell and Molecular Biology Graduate Group:
         http://www.med.upenn.edu/camb/faculty/cbp/payne.html

     International Pemphigus Foundation:
         http://www.pemphigus.org/

 

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