Aimee S. Payne, MD,PhD

Description of Research Expertise

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

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. Just as cancer therapy has moved away from targeting all dividing cells (which causes systemic toxicity) to targeting molecules or pathways specific to particular cancers, the frontier for autoantibody-mediated disease research is to not target all antibodies (which is associated with significant side effects including fatal infection), but instead to eliminate just the disease-causing antibodies or the cells that produce them.

Toward this goal, we are cloning monoclonal anti-desmoglein antibodies from PV patients in order to better define the autoimmune repertoire at the molecular genetic level. Sequence 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 our 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. Ongoing projects aim to continue to identify molecular genetic markers of the human autoantibody repertoire, 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 2012-2013:
-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/PhD, postdoctoral fellow
Eun Jung Choi, MS, research specialist
Eric Mukherjee, CAMB thesis student
Michael Cho, IGG thesis student
Courtney Rubin, MS1 medical student

Lab alumni (current position):
Preety M. Sharma, PhD (Postdoctoral fellow, Columbia University)
Takeru Funakoshi, MD (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 (Penn undergraduate)

Other Penn Appointments:
Core Director, Penn Skin Disease Research Center: http://www.med.upenn.edu/sdrc
Associate Director, Medical Scientist Training Program
Cell and Molecular Biology Graduate Group
Immunology Graduate Group
Institute for Translational Medicine and Therapeutics

Recent reviews on F1000:
Funakoshi et al, 2012:

Lunardon et al, 2012:

Mao et al, 2010:

Description of Clinical Expertise

General Dermatology
Medical Dermatology
Blistering Skin Diseases