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Adults (18-65), Geriatrics (65+)
Adults (18-65), Geriatrics (65+)
Perelman Center for Advanced Medicine
South Pavilion, 1st Floor
3400 Civic Center Boulevard
Philadelphia, PA 19104
A facility of the Hospital of the University of Pennsylvania
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Epithelial biologyGene regulatory control of epidermal homeostasisEpithelial oncogenesisTissue models of human malignancyDescription of Research:The Ridky Lab uses genetically-defined, engineered epithelial tissues as an experimental platform to study pathways driving human cancer initiation, stromal invasion, tumor-stroma interaction, metastasis, and maintenance of cancer stem cells. Tissue models of invasive malignancy are used to identify and validate new targets for potential therapeutics. To maximize the physiologic and medical relevance of our efforts, we develop experimental human tissue systems based on normal primary human cells established within an architecturally faithful native 3-D environment incorporating intact mesenchymal stroma and living stromal cells. Progression to cancer is driven by genetic changes initially identified in spontaneous tumors in humans and specifically engineered into the model tissues. Many experiments are conducted entirely in this organotypic environment, while in vivo studies utilize immunodeficient mice as hosts for the engineered tissues. These new models allow up to 10 alleles or more to be altered simultaneously in 1-2 days, permitting genetic experiments with an unprecedented degree of rapidity and complexity exceeding that previously possible in traditional genetic experimental organisms, such as transgenic mice. These new genetic models, which we refer to as "Multifunctional Human Tissue Genetics", have allowed us to directly convert multiple normal human tissues into invasive cancer via targeted, specific alterations in defined, medically-relevant genetic networks. Bioinformatics-intensive systems biology approaches are used to identify centrally-acting elements that are likely important for promoting cancer progression. To determine functional roles for specific tumor cell or stromal cell-intrinsic factors, we employ various genetic and protein level interventions, including multiplexed expression of tumor-associated mutant oncogenic drivers, tumor suppressors, and conditionally active proteins. Disruption of primary oncogenic signaling and non-oncogene addicted (NOA) pathways is achieved via RNA interference (RNAi), as well as chemical small molecule inhibitors and protein based biologic agents as a foundation for development of targeted molecular therapeutics.Lab Personnel:Andrew McNeal - Research SpecialistEmily Schapira - UPenn (2013)Kevin Liu - UPenn (2013)Vihang Nakhate - UPenn (2014)Seung Ja Oh - Postdoctoral fellowLab Web Page:http://www.med.upenn.edu/ridkylab/
Pharmacologic activation of the G protein-coupled estrogen receptor inhibits pancreatic ductal adenocarcinoma, Christopher A. Natale, Jinyang Li, Tzvete Dentchev, Brian C. Capell, John T. Seykora, Ben Z. Stanger, Todd W. Ridky: Pharmacologic activation of the G protein-coupled estrogen receptor inhibits pancreatic ductal adenocarcinoma
Cellular and Molecular Gastroenterology and Hepatology
: 2020 .
Monteleon Christine L, Lee In Young, Ridky Todd W: Exophilin-5 supports lysosome-mediated trafficking required for epidermal differentiation. The Journal of investigative dermatology 139 (10): 2219-2222.e6,2019.
Lee Vivian, Gober Michael D, Bashir Hasan, O'Day Conor, Blair Ian A, Mesaros Clementina, Weng Liwei, Huang Andrew, Chen Aaron, Tang Rachel, Anagnos Vince, Li JiLon, Roling Sophie, Sagaityte Emilija, Wang Andrew, Lin Chenyan, Yeh Christopher, Atillasoy Cem, Marshall Christine, Dentchev Tzvete, Ridky Todd, Seykora John T: Voriconazole enhances UV-induced DNA damage by inhibiting catalase and promoting oxidative stress. Experimental dermatology 29 (1): 29-38,2019.
Egolf Shaun, Aubert Yann, Doepner Miriam, Anderson Amy, Maldonado-Lopez Alexandra, Pacella Gina, Lee Jessica, Ko Eun Kyung, Zou Jonathan, Lan Yemin, Simpson Cory L, Ridky Todd, Capell Brian C: LSD1 Inhibition Promotes Epithelial Differentiation through Derepression of Fate-Determining Transcription Factors. Cell reports 28 (8): 1981-1992.e7,2019.
Ma Sophia A, O'Day Conor P, Dentchev Tzvete, Takeshita Junko, Ridky Todd W, Seykora John T, Chu Emily Y: Expression of p15 in a spectrum of spitzoid melanocytic neoplasms. Journal of cutaneous pathology 46 (5): 310-316,2019.
Monteleon Christine L, Agnihotri Tanvir, Dahal Ankit, Liu Mingen, Rebecca Vito W, Beatty Gregory L, Amavaradi Ravi K, Ridky Todd W: Lysosomes support the degradation, signaling, and mitochondrial metabolism necessary for human epidermal differentiation. The Journal of investigative dermatology 138 (9): 1945-1954,2018.
Natale Christopher A, Li Jinyang, Zhang Junqian, Dahal Ankit, Dentchev Tzvete, Stanger Ben Z, Ridky Todd W: Activation of G protein-coupled estrogen receptor signaling inhibits melanoma and improves response to immune checkpoint blockade. eLife 7 : 2018.
Taylor Laura A, O'Day Conor, Dentchev Tzvete, Hood Kyle, Chu Emily Y, Ridky Todd W, Seykora John T: p15 Expression Differentiates Nevus from Melanoma. The American journal of pathology 186 (12): 3094-3099,2016.
Duperret Elizabeth K, Natale Christopher A, Monteleon Christine, Dahal Ankit, Ridky Todd W: The integrin αv-TGFβ signaling axis is necessary for epidermal proliferation during cutaneous wound healing. Cell cycle (Georgetown, Tex.) 15 (15): 2077-86,2016.
Natale Christopher A, Duperret Elizabeth K, Zhang Junqian, Sadeghi Rochelle, Dahal Ankit, O'Brien Kevin Tyler, Cookson Rosa, Winkler Jeffrey D, Ridky Todd W: Sex steroids regulate skin pigmentation through nonclassical membrane-bound receptors. eLife 5 : 2016.
Department of DermatologyUniversity of Pennsylvania1010 Biomedical Research Building421 Curie Blvd
Patient appointments: 800-789-7366