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

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

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Assistant Professor of Dermatology
Department: Dermatology
Graduate Group Affiliations

Contact information
Department of Dermatology
University of Pennsylvania
235b Clinical Research Building
415 Curie Blvd
Philadelphia, PA 19104
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 Clinical Expertise

General Dermatology

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 EK, Ridky TW.: Kindler syndrome in mice and men. Cancer Biol Ther. 15(9), 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), Mar 12 2014

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

Ratushny V, Gober MD, Hick R, Ridky TW, Seykora JT.: From keratinocyte to cancer:the pathogenesis and modeling of cutaneous squamous cell carcinoma. J Clin Invest. 122(2): 464-72, Feb 1 2012 Notes: doi: 10.1172/JCI57415.

Ridky Todd W, Chow Jennifer M, Wong David J, Khavari Paul A: Invasive three-dimensional organotypic neoplasia from multiple normal human epithelia. Nature medicine 16(12): 1450-5, Dec 2010.

Rieger Kerri E, Ridky Todd W, Sundram Uma N: Skin nodules in a patient with acute myeloid leukemia and neurological deterioration--quiz case. Disseminated fusariosis. Archives of dermatology 146(9): 1037-42, Sep 2010.

Ridky Todd W, Khavari Paul A: The hair follicle bulge stem cell niche resists transformation by the hedgehog pathway. Cell stem cell 6(4): 292-4, Apr 2010.

Wong David J, Liu Helen, Ridky Todd W, Cassarino David, Segal Eran, Chang Howard Y: Module map of stem cell genes guides creation of epithelial cancer stem cells. Cell stem cell 2(4): 333-44, Apr 2008.

Rinn John L, Wang Jordon K, Allen Nancy, Brugmann Samantha A, Mikels Amanda J, Liu Helen, Ridky Todd W, Stadler H Scott, Nusse Roel, Helms Jill A, Chang Howard Y: A dermal HOX transcriptional program regulates site-specific epidermal fate. Genes & development 22(3): 303-7, Feb 2008.

Ridky Todd W: Nonmelanoma skin cancer. Journal of the American Academy of Dermatology 57(3): 484-501, Sep 2007.

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Last updated: 08/14/2014
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