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Dr Yanling Liao
Understanding immunity and fibrosis in RDEB
Grant Title: Identifying innate and adaptive immune mechanisms associated with fibrosis in animal models of RDEB (Recessive Dystrophic Epidermolysis Bullosa)
Investigator: Dr Yanling Liao, Assistant Professor of Pediatrics
Co-investigator: Professor Mitchell Cairo, Associate Chair of the Department of Pediatrics & Professor of Pediatrics, Medicine, Pathology, Microbiology, Immunology, Cell Biology & Anatomy at NYMC
Institution: New York Medical College, 40 Hospital Oval, Valhalla, New York, USA
Start Date: July 1st, 2020 for 3 years
Grant amount: €250,000.00
Research type: Preclinical (51% funding with DEBRA Ireland)
There are two types of inflammation, the first is microbial-mediated (e.g. the presence of bacteria), and the other one is in the absence of microbial organisms, also named sterile inflammation. A defining feature of sterile inflammation is that it can often result in a chronic inflammatory process and fibrosis. Based on our preliminary preclinical studies, it is possible that patients with RDEB could be born with sterile inflammation and further be confounded by microbial-mediated inflammation because of the lack of Collagen 7. This brings into question the systemic challenges associated with EB – far more than just a problem with the skin and mucosa. Continuous and unresolved inflammation then leads to a chronic problem, fibrosis and ultimately may be linked to the development of squamous cell carcinoma. It is therefore essential to understand the mechanisms of this early inflammatory process.
The proposed studies will involve an RDEB model that lacks COL7A1 to investigate what types of immune cells infiltrate the skin under sterile conditions. The group will also look at what molecular signals induce their infiltration, how they interact with each other and with the skin microenvironment. Based on these results, they will investigate if the molecular signals can be stopped or slowed to suppress the development of chronic inflammation and fibrosis.
Elements of the two types of immune response (innate and adaptive), have both been demonstrated to play an important role in triggering fibrosis in many organ systems such as lung and liver. However, their role in chronic inflammation and fibrosis in RDEB is remains poorly understood.
The proposed studies will investigate the sequence of immune responses and their correlation with signalling transduction in the skin to understand progression and alteration of the immune response.
It is hoped that by determining the signalling pathways, this work will reveal the mechanisms that correlate with inflammation and fibrosis, identify potential targets for early intervention and development of novel and more effective immune therapies in RDEB.
About this research and why it is important:
“It has been well recognized that chronic inflammation and fibrosis contribute to squamous cell carcinoma development in patients with RDEB. The inflammatory response, which is a natural defense system in our body, is supposed to be resolved after defending infection and/or injury, yet it is not resolved in patients with RDEB. Instead, it evolves into an unwanted chronic condition in these patients. As such, our investigations will help us identify how immune cells in the skin change with time in response to changes within the dermal microenvironment. This research will help us understand the mechanism of chronic inflammation and identify novel targets for the treatment or prevention of chronic inflammation and fibrosis in patients with RDEB.” Dr Yanling Liao
Dr. Yanling Liao obtained her Bachelor of Science in Biology at Xiamen University, P.R. China and her PhD from the Department of Biochemistry at Albert Einstein College of Medicine, New York, investigating the mechanism of RNA transcriptional regulation. She did her postdoctoral training in Dr. Helen Blau’s laboratory at the Department of Immunology & Microbiology at Stanford University School of Medicine, California, and later joined Dr. Mitchell Cairo’s laboratory in the Department of Pediatrics, Columbia University Medical Center, New York. Dr. Liao became a Research Assistant Professor of Pediatrics in 2011 and an Assistant Professor of Pediatrics in 2014 at New York Medical College, where her main research has been focused on preclinical development of stem cell and protein therapies for RDEB.
Professor Mitchell Cairo is currently the Associate Chairman and Professor (with tenure) in the Department of Pediatrics at New York Medical College (NYMC). His additional current leadership positions include being the Chief of the Division of Pediatric Hematology, Oncology and Stem Cell Transplantation, Program Director of the Adult & Pediatric BMT Program, Director of the Childhood and Adolescent Cancer and Blood Disease Center, Medical and Scientific Director of the GMP Cellular and Tissue Engineering Laboratory at Westchester Medical Center (WMC), Medical Director of the WMC Hematotherapy Program and Chair of the WMC Adult and Pediatric Cancer Program. Dr. Cairo’s additional academic appointments include being a Professor of Medicine, Pathology, Microbiology and Immunology and Cell Biology and Anatomy and Public Health at NYMC.