Todd William Ridky, M.D.,Ph.D.

faculty photo
Assistant 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
Office: 215 573 5709
B.S. (Chemistry)
University of North Carolina at Chapel Hill, 1992.
Ph.D. (Biochemistry)
Case Western Reserve University, 1997.
Case Western Reserve University School of Medicine, 1999.
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Description of Research Expertise

Epithelial biology
Gene 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:

Selected Publications

Duperret Elizabeth K, Dahal Ankit, Ridky Todd W: Focal adhesion-independent integrin αv regulation of FAK and c-myc is necessary for 3D skin formation and tumor invasion. Journal of cell science Sep 2015.

Jessica McDonald: When Moles Go Bad: Penn Scientists Identify Commonly Lost Protein That Protects Against Melanoma. NPR,, WHYY radio August 2015.

Todd Ridky interviewed by Dan Loney: Moles and Melanoma. Knowledge@Wharton SIRIUS XM National Radio Broadcast Host Dan Loney Interview with Todd Ridky regarding Moles, Melanoma, and P15 August 2015.

McNeal Andrew S, Liu Kevin, Nakhate Vihang, Natale Christopher A, Duperret Elizabeth K, Capell Brian C, Dentchev Tzvete, Berger Shelley L, Herlyn Meenhard, Seykora John T, Ridky Todd W: CDKN2B loss promotes progression from benign melanocytic nevus to melanoma. Cancer Discovery Jul 2015.

Monteleon Christine L, McNeal Andrew, Duperret Elizabeth K, Oh Seung J, Schapira Emily, Ridky Todd W: IQGAP1 and IQGAP3 Serve Individually Essential Roles in Normal Epidermal Homeostasis and Tumor Progression. The Journal of investigative dermatology 135(9): 2258-65, Apr 2015.

Ridky Todd W, Cotsarelis George: Vismodegib resistance in basal cell carcinoma: not a smooth fit. Cancer cell 27(3): 315-6, Mar 2015.

Duperret EK, Ridky TW.: Kindler syndrome in mice and men. Cancer Biol Ther. 15(9): 1113-6, Jun 11 2014 Notes: [Epub ahead of print]

Duperret EK, Oh SJ, McNeal A, Prouty SM, Ridky TW.: Activating FGFR3 mutations cause mild hyperplasia in human skin, but are insufficient to drive benign or malignant skin tumors. Cell Cycle. 13(10): 1551-9, Mar 12 2014

Duperret EK, Ridky TW.: Focal adhesion complex proteins in epidermis and squamous cell carcinoma. Cell Cycle. 12(20): 3272-85, Sep 12 2013.

Ratushny Vladimir, Gober Michael D, Hick Ryan, Ridky Todd W, Seykora John T: From keratinocyte to cancer: the pathogenesis and modeling of cutaneous squamous cell carcinoma. The Journal of clinical investigation 122(2): 464-72, Feb 2012.

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Last updated: 09/08/2015
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