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Aimee S. Payne, MD,PhD

Aimee S. Payne, MD,PhD

faculty photo
Albert M. Kligman Assistant Professor of Dermatology
Department: Dermatology
Graduate Group Affiliations

Contact information
1009 Biomedical Research Building
421 Curie Boulevard
Philadelphia, PA 19104
Office: 215-662-2737
Fax: 215-573-7173
Lab: 215-898-3232 or 215-898-8399
Education:
B.S. (Biology)
Stanford University, 1993.
MD, PhD (Molecular and Cellular Biology)
Washington University School of Medicine, 2001.
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Description of Research Expertise

Research Interests:
Genetic and functional characterization of human autoantibody repertoires
Targeted therapy for pemphigus
Regulation of desmosome assembly and disassembly

Key words: autoimmunity, human immunology, cell adhesion, dermatology, skin, cadherin, p38 MAPK

Description of Research:
Pemphigus vulgaris (PV) is a potentially fatal disorder in which autoantibodies against desmosomal cell adhesion molecules known as desmogleins cause blistering of the skin and mucous membranes. Our laboratory is interested in better understanding pathogenic mechanisms in this model organ-specific autoimmune disease, from both the immunologic and cell biologic perspectives.

A fundamental question in organ-specific autoimmune disease is why the immune system breaks tolerance against only a limited number of self-antigens. We have cloned anti-desmoglein monoclonal antibodies from PV patients to understand how they developed desmoglein autoreactivity. Genetic analysis shows that a limited number of antibody genes encode the human PV autoantibody repertoire and that there is shared VH1-46 gene usage even among different PV patients. PV antibodies using VH1-46 are autoreactive to the disease antigen in the absence of somatic mutation or require very few mutations to develop autoreactivity. Common gene usage indicates a common mechanism for developing autoimmunity in PV. Ultimately, shared structural elements of the PV autoantibody repertoire (e.g., VH or CH gene usage) may lead to safer targeted therapies for pemphigus. Ongoing projects aim to identify potential foreign antigenic triggers of the desmoglein autoimmune response in pemphigus, and to identify the B cell subsets that produce the pathogenic autoantibodies.

The human pathogenic and non-pathogenic anti-desmoglein monoclonal antibodies we have identified are unique reagents that allow for the controlled study of desmosomal cell adhesion in keratinocytes. We have shown that pathogenic anti-desmoglein antibodies prevent desmosome assembly in human keratinocytes by internalizing newly synthesized desmoglein 3, but not its presumed cellular binding partner desmocollin 3. Current studies are examining the role of cell signaling pathways, specifically the p38 MAPK/MK2 axis, in disease pathogenesis.

Laboratory projects for 2013-2014:
-Cloning and characterization of isotype-specific autoantibody repertoires from pemphigus patients
-Development and characterization of mouse models for inflammatory blistering disease
-Characterization of B lineage populations in pemphigus
-Role of p38 signaling pathways in desmosomal cell adhesion

Lab personnel:
Xuming Mao, MD/PhD, research associate
Christoph Ellebrecht, MD, postdoctoral fellow
Eun Jung Choi, MS, research specialist
Eric Mukherjee, CAMB thesis student
Michael Cho, IGG thesis student

Lab alumni (current position):
Preety M. Sharma, PhD (Associate Research Scientist, Columbia University)
Takeru Funakoshi, MD, PhD (Dermatology faculty, Keio University, Japan)
Luisa Lunardon, MD (Dermatology faculty, University of Milan)
Arielle R. Nagler, MD (Dermatology resident, New York University)
Sara A. Farber (Medical Student, University of Pennsylvania)
Zachary Hostetler (MSTP student, University of Pennsylvania)
Peter Chansky (Medical student, University of Pennsylvania)
Courtney Rubin (Medical student, University of Pennsylvania)

Other Penn Appointments:
Associate Director, Medical Scientist Training Program
Immunology Graduate Group
Cell and Molecular Biology Graduate Group
Institute for Translational Medicine and Therapeutics

Description of Clinical Expertise

General Dermatology
Medical Dermatology
Blistering Skin Diseases

Selected Publications

Cho MJ, Lo ASY, Mao X, Nagler AR, Ellebrecht CT, Mukherjee EM, Hammers CM, Choi EJ, Sharma PM, Uduman M, Li H, Rux AH, Farber SA, Rubin CB, Kleinstein SH, Sachais BS, Posner MR, Cavacini LA, Payne AS: Shared VH1-46 gene usage by pemphigus vulgaris autoantibodies indicates common humoral immune responses among patients. Nature Commun. doi: 10.1038/ncomms5167, 2014.

Mao X, Li H, Sano Y, Gaestel M, Park JM, Payne AS.: MAPKAP kinase 2 (MK2)-dependent and independent models of blister formation in pemphigus vulgaris. J. Invest. Dermatol. 134: 68-76, Jan 2014.

Funakoshi T, Lunardon L, Ellebrecht CT, Nagler AR, O’Leary CE, Payne AS. : Enrichment of total serum IgG4 in pemphigus patients. Br.J.Dermatol. 167: 1245-1253, 2012.

Lunardon L, Payne AS.: Inhibitory human anti-chimeric antibodies to rituximab in a pemphigus patient. J.Allerg.Clin.Immunol. 130: 800-803, 2012.

Lunardon L, Tsai KJ, Propert KJ, Fett N, Stanley JR, Werth VP, Tsai DE, Payne AS.: Adjuvant rituximab therapy of pemphigus: a single center experience with 31 patients. Arch.Dermatol. 148(9): 1031-1036, 2012.

Mao X, Sano Y, Park JM, Payne AS: p38 mitogen activated protein kinase (MAPK) activation is downstream of the loss of intercellular adhesion in pemphigus vulgaris. J.Biol.Chem. 286: 1283-1291, 2011.

Mao X, Nagler AR, Farber SA, Choi EJ, Jackson LH, Leiferman KM, Ishii N, Hashimoto T, Amagai M, Zone JJ, Payne AS: Autoimmunity to desmocollin 3 in pemphigus vulgaris. Am.J.Pathol. 177: 2724-2730, 2010.

Sharma PM, Choi EJ, Ishii K, Payne AS.: Pathogenic anti-desmoglein monoclonal antibodies demonstrate variable ELISA activity because of preferential binding of mature versus proprotein isoforms of desmoglein 3. Journal of Investigative Dermatology 129: 2309-2312, 2009.

Mao X, Choi EJ, Payne AS: Disruption of desmosome assembly by monovalent human pemphigus vulgaris monoclonal antibodies. Journal of Investigative Dermatology 129: 908-918, 2009.

Murrell DF, Dick S, Ahmed AR, Amagai M, Barnadas MA, Borradori L, Bystryn JC, Cianchini G, Diaz L, Fivenson D, Goldsmith L, Hall R, Harman K, Hashimoto T, Hertl M, Hunzelmann N, Iranzo P, Joly P, Jonkman M, Kitajima Y, Korman N, Martin LK, Mimouni D, Payne AS, Rubenstein D, Shimizu H, Sinha A, Sirois D, Zillikens D, Werth VP: Consensus statement on definitions of disease endpoints and therapeutic response for pemphigus. Journal of the American Academy of Dermatology 58: 1043-1046, 2008.

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Last updated: 11/05/2014
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