Aimee S. Payne, MD,PhD

faculty photo
Albert M. Kligman Associate Professor of Dermatology
Department: Dermatology

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
Graduate Group Affiliations
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 anti-desmoglein B cell repertoires
Targeted therapy for pemphigus
Regulation of desmosome adhesion

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 B cell repertoires from PV patients to understand how they developed desmoglein autoreactivity. We have identified shared VH1-46 gene usage in anti-desmoglein 3 B cells from different PV patients and defined acidic amino acid residues that are necessary and sufficient to confer desmoglein 3 autoreactivity. These VH1-46 B cells are autoreactive to the disease antigen in the absence of somatic mutation or require very few mutations to develop autoreactivity, which may favor their selection early in the immune response. Common VH gene usage is significant, because it may indicate common mechanisms for developing autoimmunity in PV. Ultimately, shared structural elements of the PV B cell 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, to identify the B cell subsets that produce the pathogenic autoantibodies, and to develop effective targeted therapies.

Our laboratory is also investigating the cell regulatory pathways that promote desmosomal adhesion. We have shown that the p38 MAPK/MK2 axis is a critical regulator of desmosomal adhesion in keratinocytes and that inhibition of this pathway can ameliorate pemphigus skin blistering. Ongoing projects are studying the regulation of desmosomal adhesion and desmosomal protein expression in keratinocytes to better understand how anti-desmoglein antibodies cause the loss of cell adhesion and how we might interfere with these pathways to improve disease.

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
Shantan Gujja Reddy, research specialist

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 faculty, 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

Selected Publications

Ellebrecht CT, Choi EJ, Allman DM, Tsai DE, Wegener WA, Goldenberg DM, Payne AS: Subcutaneous veltuzumab, a humanized anti-CD20 antibody, for treatment of refractory pemphigus vulgaris. JAMA Dermatol. 150: 1331-1335, 2014.

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. 5: 4167, 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.

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: 08/03/2015
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