Faculty
Todd William Ridky, M.D.,Ph.D.
Associate Professor of Dermatology
Department: Dermatology
Graduate Group Affiliations
Contact information
Department of Dermatology
University of Pennsylvania
1010 Biomedical Research Building
421 Curie Blvd
Philadelphia, PA 19104
University of Pennsylvania
1010 Biomedical Research Building
421 Curie Blvd
Philadelphia, PA 19104
Office: 215 573 5709
Publications
Education:
B.S. (Chemistry)
University of North Carolina at Chapel Hill, 1992.
Ph.D. (Biochemistry)
Case Western Reserve University, 1997.
M.D.
Case Western Reserve University School of Medicine, 1999.
Cert. (Research Mentor Training: Effective Communication and Aligning Expectations)
University of Pennsylvania, 2022.
B.S. (Chemistry)
University of North Carolina at Chapel Hill, 1992.
Ph.D. (Biochemistry)
Case Western Reserve University, 1997.
M.D.
Case Western Reserve University School of Medicine, 1999.
Cert. (Research Mentor Training: Effective Communication and Aligning Expectations)
University of Pennsylvania, 2022.
Links
Search PubMed for articles
Society for Investigative Dermatology
American Association for Cancer Research
Ridky Lab Web Page
Permanent linkSearch PubMed for articles
Society for Investigative Dermatology
American Association for Cancer Research
Ridky Lab Web Page
Description of Clinical Expertise
General DermatologyDescription of Research Expertise
Epithelial biologyGene regulatory control of epidermal homeostasis
Epithelial oncogenesis
Tissue models of human malignancy
Description 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 Specialist
Emily Schapira - UPenn (2013)
Kevin Liu - UPenn (2013)
Vihang Nakhate - UPenn (2014)
Seung Ja Oh - Postdoctoral fellow
Lab Web Page:
http://www.med.upenn.edu/ridkylab/
Selected Publications
Lee I, Doepner M, Weissenrieder J, Majer AD, Mercado S, Estell A, Natale CA, Sung PJ, Foskett JK, Carroll MP, Ridky TW.: LNS8801 inhibits Acute Myeloid Leukemia by Inducing the Production of Reactive Oxygen Species and Activating the Endoplasmic Reticulum Stress Pathway. Cancer Res Commun 3: 1594-1606, Aug 2023.Hatterschide J, Natale CA, Ridky TW, White EA.: Monitoring cell fate in 3D organotypic human squamous epithelial cultures. STAR Protoc 4: 102101, Mar 2023.
Kohli J, Ge C, Fitsiou E, Doepner M, Brandenburg SM, Faller WJ, Ridky TW, Demaria M.: Targeting anti-apoptotic pathways eliminates senescent melanocytes and leads to nevi regression. Nat Commun 13: 7923, Dec 2022.
Doepner M, Lee I, Natale CA, Brathwaite R, Venkat S, Kim SH, Wei Y, Vakoc CR, Capell BC, Katzenellenbogen JA, Katzenellenbogen BS, Feigin ME, Ridky TW.: Endogenous DOPA inhibits melanoma through suppression of CHRM1 signaling. Sci Adv 8: eabn4007, Sep 2022.
Aguirre-Portolés C, Payne R, Trautz A, Foskett JK, Natale CA, Seykora JT, Ridky TW.: ZIP9 Is a Druggable Determinant of Sex Differences in Melanoma. Cancer Res 81: 5991-6003, Dec 2021.
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 Notes: in press.
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, Oct 2019 Notes: doi: 10.1016/j.jid.2019.04.014. Epub 2019 May 11.
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, Sep 2019 Notes: doi: 10.1111/exd.14038 [Epub ahead of print]
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, Aug 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, May 2019.
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