Jiang Chen, M.D.
12800 East 19th Avenue, RC-1 North, P18-8126
Mail Stop 8320, P.O. Box 6511
Aurora, CO 80045
Department of Dermatology
Charles C. Gates Center for Regenerative Medicine and Stem Cell Biology
Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, 2002 – 2007
M.D. in Internal Medicine, University of Heidelberg, Germany, 2001
Utilizing pre-clinical models to test novel therapeutic strategies for genetic skin diseases
Keratin mutations can result in the development of epidermal diseases, such as epidermolytic hyperkeratosis (EHK), epidermalysis bullosa simplex (EBS) and pachyonychia congenita (PC). Tremendous progress had been made in the understanding of the etiology and pathological development of these diseases. New and promising therapies are being actively developed. However, there is no effective and permanent treatment yet available for these conditions. We are using cell- and gene-based approaches to target mutant keratin genes in in vivo mouse models developed in the laboratory of Dr. Dennis Roop. Major goals of our research include the development of humanized mouse models, gene and mutation-specific targeting, safe and robust epidermal delivery, and ultimately, gene correction in epidermal keratinocyte stem cells.
Hair follicle as a model to understand signaling pathways involved in skin development and homeostasis
Hair follicle is a unique skin appendage existing only in mammals. The development and maintenance of the hair follicles require extensive interactions between the epidermal keratinocytes and the dermal fibroblasts, and involve tightly regulated interactions of a number of major molecular signaling pathways, including Wnt and Shh. Genes of the planar cell polarity (PCP) signaling pathway, a non-canonical Wnt (PCP/Wnt) signaling pathway, are involved in hair follicle development, controlling the orientation and differentiation of hair follicles. During hair follicle morphogenesis, PCP genes are essential for the formation of primary cilium, a specialized cellular protrusion that processes the Shh signals. Thus, the hair follicle is an excellent model to understand the roles of PCP, primary cilia and Shh signaling in controlling epidermal keratinocyte proliferation, migration, differentiation and cell-cell communication. The main focus of our research is to use mutant mouse models of genes involved in the PCP signaling pathway to determine how PCP signaling controls keratinocyte competence and responsiveness during hair follicle morphogenesis. Knowledge gained from our research will provide important insights into hair loss and the development of skin cancers.
· Bilousova G, Chen J and Roop DR (2010). Differentiation of Mouse Induced Pluripotent Stem Cells into a Multipotent Keratinocyte Lineage. J Investig Dermatol (In press).
· Dai D, Zhu H, Wlodarczyk B, Zhang L, Li AG, Finnell RH, Roop DR and Chen J (2010). Fuz is a PCP effector gene that controls the morphogenesis and differentiation of hair follicles. J Investig Dermatol (In press).
· Chen J, Li L, Chen J, Zeng Y, Xu H, Song Y and Wang B (2010). Sera of Elderly Bullous Pemphigoid Patients with Associated Neurological Diseases Recognize Bullous Pemphigoid Antigens in the Human Brain. Gerontology 2010 Jul 21 [Epub ahead of print].
· Li F, Huang Q, Chen J, Peng Y, Roop DR, Bedford JS, Li CY (2010). Apoptotic cells activate the "phoenix rising" pathway to promote wound healing and tissue regeneration. Sci Signal. 23:ra13 (Cover story).
· Chen J, Roop DR (2008). Genetically engineered mouse models for skin research: taking the next step. J Dermatol Sci. 52:1-12 (Review).
· Chen J, Jaeger K, Den Z, Koch PJ, Sundberg JP and Roop DR (2008). Mice expressing a mutant Krt75 (K6hf) allele develope hair and nail defects resembling pachyonychia congenita. J Investig Dermatol. 128:270-9 (Cover story).
· Andrassy M, Igwe J, Autschbach F, Volz C, Remppis A, Neurath MF, Schleicher E, Humpert PM, Wendt T, Liliensiek B, Morcos M, Schiekofer S, Thiele K, Chen J, Kientsch-Engel R, Schmidt AM, Stremmel W, Stern DM, Katus HA, Nawroth PP, Bierhaus A (2006). Posttranslationally modified proteins as mediators of sustained intestinal inflammation. Am J Pathol. 169:1223-37.
· Schiekofer S, Franke S, Andrassy M, Chen J, Rudofsky G, Schneider JG, von Eynatten M, Wendt T, Mocos M, Kientdch-Engel R, Stein G, Schleicher E, Nawroth PP and Bierhaus A (2006). Postprandial mononuclear NF-kappaB activation is independent of the AGE-content in a single meal. Exp Clin Endocrinol Diabetes. 114:1-8.
· Chen J, Roop DR (2005) Mouse models in preclinical studies for pachyonychia congenita. J Investig Dermatol Symp Proc. 10:37-46 (Review).
· Chen J, Kasper M, Heck T, Nakagawa K, Humpert PM, Bai L, Wu G, Zhang Y, Luther T, Andrassy M, Schiekofer S, Hamann A, Morcos M, Chen B, Stern DM, Nawroth PP, Bierhaus A (2005). Tissue factor as a link between wounding and tissue repair. Diabetes. 54:2143-54.
· Schiekofer S, Rudofsky G Jr, Andrassy M, Schneider J, Chen J, Isermann B, Kanitz M, Elsenhans S, Heinle H, Balletshofer B, Haring HU, Schleicher E, Nawroth PP, Bierhaus A (2003) Glimepiride reduces mononuclear activation of the redox-sensitive transcription factor nuclear factor-kappa B. Diabetes Obes Metab. 5:251-61.
· Schiekofer S, Andrassy M, Chen J, Rudofsky G, Schneider J, Wendt T, Stefan N, Humpert P, Fritsche A, Stumvoll M, Schleicher E, Häring H, Nawroth P, Bierhaus A (2003). Acute Hyperglycemia Causes Intracellular Formation of CML and Activation of ras, p42/44 MAPK, and Nuclear Factor B in PBMCs. Diabetes 52: 621-633.
· Andrassy M, Bierhaus A, Hong M, Sis J, Schiekofer S, Humper PM, Chen J, Haap M, Renn W, Schleicher E, Haring H, Andrassy K, Nawroth PP (2002). Erythropoietin-mediated decrease of the redox-sensitive transcription factor NF-kappaB is inversely correlated with the hemoglobin level. Clin Nephrol. 58:179-89.
· Bierhaus A, Schiekofer S, Schwaninger M, Andrassy M, Humpert PM, Chen J, Hong M, Luther T, Henle T, Kloting I, Morcos M, Hofmann M, Tritschler H, Weigle B, Kasper M, Smith M, Perry G, Schmidt AM, Stern DM, Haring HU, Schleicher E, Nawroth PP (2001). Diabetes-Associated Sustained Activation of the Transcription Factor Nuclear Factor-kappaB. Diabetes 50:2792-808.
· Bierhaus A, Andrassy M, Schiekofer S, Chen J, Humpert P, Bai L, Chen B, Schleicher E, Nawroth P (2001). Endothelzellaktivierung bei Diabetes mellitus. Haemostaseologie. 21:151-8 (Review).
· Chen J, Bierhaus A, Schiekofer S, Andrassy M, Chen B, Stern D, Nawroth P (2001). Tissue factor--a receptor involved in the control of cellular properties, including angiogenesis. Thromb Haemost. 86:334-45 (Review).
· Bierhaus A, Chen J, Liliensiek B, Nawroth P (2000). LPS and cytokine activated endothelium. Semin Thromb Hemost. 26:571-88 (Review).
· Abe K, Shoji M, Chen J, Bierhaus A, Danave I, Micko C, Casper K, Dillehay D, Nawroth P, Rickles F (1999). Regulation of vascular endothelial growth factor production and angiogenesis by the cytoplasmic tail of tissue factor. Proc Natl Acad Sci U S A. 96:8663-8.
· Zhang Y, Weiler-Guettler H, Chen J, Wilhelm O, Deng Y, Qiu F, Nakagawa K, Klevesath M, Wilhelm S, Bohrer H, Nakagawa M, Graeff H, Martin E, Stern D, Rosenberg R, Ziegler R, Nawroth P (1998). Thrombomodulin modulates growth of tumor cells independent of its anticoagulant activity. J Clin Invest. 101:1301-9.