Aimee S. Payne, MD, PhD -- Dermatology Faculty

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:

Pemphigus is a model organ-specific autoimmune disease in which antibodies against desmosomal cell adhesion molecules known as desmogleins cause potentially fatal skin blistering. We are interested in defining the autoimmune repertoire in pemphigus at the molecular genetic level in order to better understand disease pathogenesis and develop more specific, and potentially safer, treatments.

Using phage display, we have isolated monoclonal anti-desmoglein antibodies from patients with active pemphigus vulgaris (PV). Genetic analysis shows that a limited number of antibody genes encode the human PV autoantibody repertoire, with different genes for pathogenic and non-pathogenic antibodies, and shared genes even among different PV patients. 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 the feasibility of pathogenic antibody-targeted therapy.

Using the PV monoclonal antibodies that we have identified, we have shown that pathogenic anti-desmoglein antibodies prevent desmosome assembly in human keratinocytes. Current studies are focused on better defining mechanisms for the loss of cell adhesion.

Lab Members:

Eun Jung Choi, M.S. - Research Assistant

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

Arielle Nagler - Medical Student

Alumni:

Preety Sharma, 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.

Mao X and Payne AS. (2008) Seeking approval: Present and future therapies for pemphigus vulgaris.
Curr. Opin. Invest. Drugs, 9(5):497-504

Murrell DF, Dick S, Ahmed AR, et al. (2008) Consensus statement on
definitions of disease, end points, and therapeutic response for pemphigus. J. Am. Acad. Dermatol, 58: 1043-1046

    Mao X, Choi EJ, Payne AS. (2009) Disruption of desmosome assembly
    by monovalent human pemphigus vulgaris monoclonal antibodies.
    J.Invest.Dermatol., doi: 10.1038/jid.2008.339, in press.

    Sharma PM, Choi EJ, Ishii K, Payne AS. (2009) Pathogenic anti-
    desmoglein monoclonal antibodies demonstrate variable ELISA activity
    due to preferential binding of mature versus proprotein isoforms of     desmoglein 3. J.Invest.Dermatol., doi: 10.1038/jid.2009.41, in
    press.

    Rosenbach M, Murrell DF, Bystryn J-C, Dulay S, Dick S, Fakharzadeh
    SS, Hall R, Korman NJ, Lin J, Okawa J, Pandya AG, Payne AS, Rose M,
    Rubenstein D, Woodley D, Vittorio C, Werth BB, Williams EA, Taylor L,
    Troxel A, Werth VP. (2009) Reliability and convergent validity of two
    outcome instruments for pemphigus.
     J.Invest.Dermatol, doi: 10.1038/jid.2009.72., in press.

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/

	Aimee S. Payne, M.D., Ph.D. *Assistant Professor* *Clinical:* Perelman Center for Advanced Medicine Suite 1-330S 3400 Civic Center Boulevard Philadelphia, PA 19104 Tel: 215-662-2737 Fax: 215-662-4131 *Office:* 217A Clinical Research Building 415 Curie Blvd. Philadelphia, PA 19104 Fax: 215-573-7173 Email:paynea@mail.med.upenn.edu (Research purposes only; all patient communication should be directed to 215-662-2737)