Precision Immunology Institute

Inflammatory Skin Diseases

The inflammatory skin diseases laboratory at the Icahn School of Medicine at Mount Sinai (ISMMS) made paradigm-shifting discoveries on the immunologic basis of atopic dermatitis/eczema and its different phenotypes in humans, enriching the understanding of its pathophysiology, ultimately opening the door to new therapeutics. The discoveries from the research done in the laboratory are now translating to new treatments and to clinical trials with novel therapeutic targets for atopic dermatitis. The laboratory also studies the role of inflammatory pathways and immune-barrier interactions in patients with inflammatory skin diseases, including atopic dermatitis/eczema, alopecia areata, ichthyosis vulgaris, contact hypersensitivity, and other inflammatory conditions.

Members of the laboratory have close collaborations with faculty members of the allergy group, including Hugh Sampson, Anna Nowak, and Scott Sicherer in an attempt to understand the “allergic” associations of atopic dermatitis and develop prevention strategies for the atopic march.

We are also building collaborations with Brian Brown to explore some of the human findings in mouse models of alopecia areata and other inflammatory skin diseases.

Collaborations are also being established with the immune-monitoring center at ISMMS, to be able to perform high scale phenotyping of multiple immune cells in both skin and blood of patients with inflammatory skin diseases.

Investigators with a major focus in transplant include:

Emma Guttman-Yassky, MD, PhD is Professor of Dermatology and Immunology and Vice Chair for research in the Department of Dermatology. She is the Director of the Center for Excellence in Eczema and the Director of the Laboratory for Inflammatory Skin Diseases at the Icahn School of Medicine at Mount Sinai in New York. The Guttman’s lab studies the role of inflammatory pathways and immune-barrier interactions in patients with inflammatory skin diseases, including atopic dermatitis, alopecia araeta, contact hypersensitivity, and other inflammatory conditions. The lab is also focusing on phenotyping T-cells, B-cells, and dendritic cells in different inflammatory skin diseases and understanding their contribution to the development or progression of the disease phenotype. Another major focus of the laboratory is to define and test additional therapeutic targets for inflammatory skin disease to ultimately benefit patients, and to define biomarkers of disease and biomarkers of therapeutic response. Dr. Guttman’s lab made paradigm-shifting discoveries on the immunologic basis of AD in humans, enriching the understanding of its pathophysiology, opening the door to new therapeutics. Dr. Guttman has developed comprehensive molecular maps of AD, defining skin differentiation and immune-circuits characterizing this disease. Her research on atopic dermatitis/eczema has contributed directly to the therapeutic developments for this disease, earning her a unique place in dermatology and immunology worldwide. She has recently also extended her research interest to alopecia areata in which her findings are also translated to possible novel therapeutic targets. Dr. Guttman has authored more than 120 primary papers and reviews in high profile journals, and secured extensive NIH, foundation and private funding for her translational studies in human. The work of the lab now has resulted in development of new treatments for inflammatory skin diseases.

Area(s) of Focus:
Skin Inflammatory Disease

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Dr. Sergio Lira received his MD from the Universidade Federal de Pernambuco in Brazil (1982) and his PhD in Physiology and Pharmacology from the University of California at San Diego (1988). He did his postdoctoral training at the Roche Institute for Molecular Biology in Nutley, NJ. After his postdoctoral training he worked for 11 years in the pharma sector, first at Bristol-Myers Squibb (1992-1996) and then at Schering-Plough (1996-2002). Dr Lira joined Mount Sinai in 2002 as the Irene Diamond Associate Professor of Immunology. In 2007 he became the co-Director of the Immunology Institute (with Dr. Lloyd Mayer), and in 2013 was promoted to Director, a position he occupied until 2016. He is currently The Leona M. and Harry B. Hemsley Charitable Trust Professor of Immunology. His research focuses on the role of immune cells and the microbiome in mucosal inflammation and cancer. He has organized international meetings in this field, including the 2003 Keystone Symposium on Chemokines and the 2006 Gordon Research Conference on Chemotactic Cytokines. He was elected to the Henry Kunkel Society in 2006 and to the Association of American Physicians in 2008. Dr. Lira was a Visiting Professor at the Southern Medical University in Guangzhou, China (2013-2016) and is a member of the Board of Scientific Counselors of the National Cancer Institute (2013-present).

Area(s) of Focus:
Inflammatory Bowel Disease
Autoimmunity
Cancer Immunology
Microbiome
Skin Inflammatory Disease

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Adrian Ting, PhD is an Associate Professor of Medicine/Immunology. His lab studies how ubiquitination affects cellular survival and death, as well as inflammatory signaling pathways. The lab discovered that non-degradative K63-linked polyubiquitination of the signaling molecule RIPK1, or the lack thereof, determines whether cell survival or cell death ensues in response to TNF. Ubiquitination of RIPK1 serves to function as an early cell death checkpoint in TNF signaling and blocking this process leads to apoptosis and necroptosis. Central to converting RIPK1 to a death-signaling molecule is its upstream regulator CYLD, a tumor suppressor and a deubiquitinating enzyme that preferentially removes K63-linked polyubiquitin chains from RIPK1. In recent years, the lab has shifted its focus to post-translational mechanisms (PTM) that inhibit CYLD, which has to be kept inactive to prevent inappropriate cell death. These inhibitory PTM include phosphorylation, proteolysis and degradation. Disruption of these inhibitory mechanisms led to excessive CYLD/RIPK1-mediated cell death and inflammation in multiple tissues including the skin, lung, and liver. The role of this CYLD-mediated cell death in physiological responses to microbial infections is currently under investigation. Furthermore, the role of this cell death in pathologies such as inflammatory disorders, transplantation and cancer are also under investigation. The goal of the lab is to thoroughly characterize the regulation and function of this cell death pathway so that rationally designed drugs can be developed to disrupt it for therapeutic purposes.

Area(s) of Focus:
Cancer Immunology
Immunodeficiency
Skin Inflammatory Diseases
Transplant 

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