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Anthony ORO
Chromatin dynamics in diagnosis and therapy Program in Epithelial Biology Stanford University School of Medicine, US |
Abstract
Proper ectodermal patterning during human development requires the concerted action of regional mesodermal and ectodermal transcription factors (TFs) that provide precise spatial and temporal regulatory information; however, the mechanism by which these factors act to stably pattern gene expression and lineage commitment remains poorly understood. We have taken a multi-dimensional genomics approach to detail the chromatin dynamics of skin using an embryonic stem differentiation method that leads to graftable human skin. We have now used this skin chromatin dynamic map to improve the efficiency and specificity of cellular manufacturing of CRISPR-corrected autologous induced pluripotent cell-derived skin to heal the wounds of patients with Recessive Dystrophic Epidermolysis Bullosa. Along with the regenerative therapies, we have used the map to identify and dissect the mechanism of disease genes involved in cleft lip/cleft palate. Iterative increases in the resolution of the chromatin dynamic map within different skin lineages and novel informatic approaches will facilitate additional disease diagnoses and therapies for previously incurable epithelial diseases.
Proper ectodermal patterning during human development requires the concerted action of regional mesodermal and ectodermal transcription factors (TFs) that provide precise spatial and temporal regulatory information; however, the mechanism by which these factors act to stably pattern gene expression and lineage commitment remains poorly understood. We have taken a multi-dimensional genomics approach to detail the chromatin dynamics of skin using an embryonic stem differentiation method that leads to graftable human skin. We have now used this skin chromatin dynamic map to improve the efficiency and specificity of cellular manufacturing of CRISPR-corrected autologous induced pluripotent cell-derived skin to heal the wounds of patients with Recessive Dystrophic Epidermolysis Bullosa. Along with the regenerative therapies, we have used the map to identify and dissect the mechanism of disease genes involved in cleft lip/cleft palate. Iterative increases in the resolution of the chromatin dynamic map within different skin lineages and novel informatic approaches will facilitate additional disease diagnoses and therapies for previously incurable epithelial diseases.
Bio
Dr. Oro is the Eugene and Gloria Bauer Professor of Dermatology at Stanford University, Program in Epithelial Biology, Associate Director of the Center for Definitive and Curative Medicine, and co-director of the Child Health Research Institute. Dr. Oro uses the skin to address mechanistic question in regenerative medicine, cancer, and autoimmunity. He has a longstanding interest in the mechanisms of hedgehog signaling in the pathogenesis of the most common human tumor, basal cell carcinoma of the skin, recently focusing on tumor evolution and novel resistance-associated signaling pathways. He has identified several novel cancer pathways and focuses on developing inhibitors for treating resistant cancer. His interest in skin development and early ectodermal differentiation has led to the development of in vitro human skin differentiation protocols and genome editing tools to produce clinical scale, corrected, autologous human skin from patient-specific induced pluripotent cells.
Dr. Oro is the Eugene and Gloria Bauer Professor of Dermatology at Stanford University, Program in Epithelial Biology, Associate Director of the Center for Definitive and Curative Medicine, and co-director of the Child Health Research Institute. Dr. Oro uses the skin to address mechanistic question in regenerative medicine, cancer, and autoimmunity. He has a longstanding interest in the mechanisms of hedgehog signaling in the pathogenesis of the most common human tumor, basal cell carcinoma of the skin, recently focusing on tumor evolution and novel resistance-associated signaling pathways. He has identified several novel cancer pathways and focuses on developing inhibitors for treating resistant cancer. His interest in skin development and early ectodermal differentiation has led to the development of in vitro human skin differentiation protocols and genome editing tools to produce clinical scale, corrected, autologous human skin from patient-specific induced pluripotent cells.
Chair
Srikala Raghavan, ASRL
Srikala Raghavan, ASRL