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
235b Clinical Research Building
415 Curie Blvd
Philadelphia, PA 19104
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, 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:
http://www.med.upenn.edu/ridkylab/

Selected Publications

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.

Zhang Jennifer Y, Adams Amy E, Ridky Todd W, Tao Shiying, Khavari Paul A: Tumor necrosis factor receptor 1/c-Jun-NH2-kinase signaling promotes human neoplasia. Cancer research 67(8): 3827-34, Apr 2007.

Truong Amy B, Kretz Markus, Ridky Todd W, Kimmel Robin, Khavari Paul A: p63 regulates proliferation and differentiation of developmentally mature keratinocytes. Genes & development 20(22): 3185-97, Nov 2006.

Ridky Todd W, Khavari Paul A: Pathways sufficient to induce epidermal carcinogenesis. Cell cycle (Georgetown, Tex.) 3(5): 621-4, May 2004.

Ortiz-Urda Susana, Elbe-B├╝rger Adelheid, Smolle Josef, Marquart Yvonne, Chudnovsky Yakov, Ridky Todd W, Bernstein Pamela, Wolff Klaus, Rappersberger Klemens: The plant lectin wheat germ agglutinin inhibits the binding of pemphigus foliaceus autoantibodies to desmoglein 1 in a majority of patients and prevents pathomechanisms of pemphigus foliaceus in vitro and in vivo. Journal of immunology (Baltimore, Md. : 1950) 171(11): 6244-50, Dec 2003.

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Last updated: 02/21/2013
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