This research portfolio consists of basic, translational and clinical studies of extracellular matrix (ECM) biology and diseases. Studies of dermal wound healing, normal and impaired, as well as studies of diseases related to cutaneous vasculature and neuroendocrine/sensory functions are also parts of this portfolio.
Basic studies encompass investigations of cellular function and regulation in the dermis under normal and disease conditions. Molecular studies include investigations of ECM protein components (collagens, fibrillins, elastins, fibulins, matrix metalloproteinases, etc.) of dermis, their structure, assembly and synthesis. A key area of the basic research is elucidating the networks of regulatory pathways that control ECM function and repair, as well as their roles in epithelial and mesenchymal (epidermal and dermal) interaction. A substantial portion of the portfolio is devoted to translational and clinical studies. These studies include unveiling mechanisms underlying ECM diseases (e.g., fibrosis, scleroderma, etc.), discovering and analyzing mutations in ECM components and constructing animal models of human ECM diseases (e.g., Marfan syndrome, pseudoxanthoma elasticum). Many ECM diseases are inheritable (e.g., Marfan syndrome, Ehlers-Danlos syndrome, venous malformation, etc.); hence, the heritable pattern and the effect of genetic background on the severity of these diseases are also subjects of studies in this portfolio.
Research into the role of ECM in wound healing is another major component of this portfolio. The goal of supporting this type of research is to meet the challenge of hyperscaring and keloids during rehabilitation of human skin wounds. Studies in this portfolio thus cover investigations aimed at understanding impaired skin wound healing that leads to over-exuberant healing, (e.g., hypertrophic scar and keloids), and, on the other hand, efforts in interventions to reduce scarring through promoting regenerative process with biological (e.g., stem cells) and engineering (e.g., bioactive materials) means.
Research on cutaneous vascular anomalies includes projects aiming at understanding the genetics and biochemical mechanisms of venous malformation, improving treatment of diseases such as hemangioma, port-wine stain birthmarks, etc., and developing new therapeutic modalities (e.g., endothelial stem cells, etc.).
- Research on the biology of adipocytes, including their functions in skin homeostasis, repair after injury, and disease;
An emerging area in the portfolio is research in the neuroendocrine/sensory aspect of skin. The research in this area includes studying skin innervation, defining sensory functions of resident skin cells (e.g., keratinocytes, Merkel cells, components of hair follicle); studying mechanisms of itch and pain and defining their mediators in skin under both normal and pathological conditions; studying mechanisms of touch and temperature sensation; investigating interactions among skin sensations, i.e., itch, pain, touch, and temperature; developing therapeutic methods to control itch and pain in disease conditions, investigating the role of skin innervation in normal tissue and in pathological conditions such as inflammation and chronic wounds. For understanding skin’s endocrine function, the portfolio covers studies of skin’s function as hormonal producer, regulator and responder, skin’s circadian rhythem and the mutual influence of psychology and skin physiology under normal and pathological conditions.
This program consists of two components: 1) Epidermal Repair and Regeneration; 2) Melanocyte Biology. Basic, translational and clinical studies of these two areas of research are covered by this program.
Aspects of keratinocyte behavior during the wound healing process (e.g., proliferation, migration, cytokine response and regulation) comprise a major part of this program. Basic studies of the normal and abnormal epithelial wound healing process are another focus of the program. The program also contains translational and clinical studies on treating chronic wound, ranging from animal model creation, devise testing and clinical trials. The program also reflects an increasing use of epithelial and mesenchymal stem cells in treating chronic wound and tissue engineering, and artificial tissue/organ construction in epidermal regeneration.
The Melanocyte Biology component includes studies of normal melanocyte development, differentiation, maintenance, regulation and the pigmentation process of skin and its appendages. An emerging area of research is melanocyte stem cell identification and its regulation. In general, melanoma studies (i.e., tumorigenesis, metastasis and treatment) are not part of the NIAMS Melanocyte Biology Program. However, studies concerning the prevention of melanocyte tumorigenesis are considered within the mission of the program. Autoimmunity caused pigmentation deficiency is considered in the NIAMS Skin Immunity Program, and is not included in the Melanocyte Biology Program.