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Embryonic signaling pathways in development, regeneration, and cancer

Andrzej Dlugosz, MD

The long-term goal of Dr. Dlugosz's laboratory is to gain a deeper understanding of the molecular and biochemical alterations involved in the initiation, progression, and maintenance of non-melanoma skin cancer, with the ultimate goal of improving patient care. The central focus of much of his work has been the Hedgehog (Hh) pathway, which regulates a variety of events throughout embryogenesis, including growth of hair follicles and formation of sebaceous oil glands. Precisely timed, cyclical activation of Hh signaling after birth is also responsible for postnatal hair follicle growth, while deregulated activation of the Hh pathway in adult tissues is responsible for basal cell carcinoma (BCC), the most common cancer in humans, and contributes to the pathogenesis of several other types of cancer.
Using a variety of mouse models, many of which were developed in his laboratory, Dr. Dlugosz has been addressing key questions related to the oncogenic functions of the Hh pathway both in BCC and other cancers, particularly medulloblastoma and gastric cancer.

  1. Is deregulated Hh signaling sufficient to initiate development of BCC or other cancers?
  2. Is continued Hh signaling required for tumor maintenance?
  3. Does the Hh pathway interact with other pathways to cause cancer?
  4. Which cell types are competent to give rise to Hh pathway-driven cancer?

In addition, Dr. Dlugosz continues to investigate the normal functions of the Hh pathway and interacting pathways in adult tissues. These studies may provide insight into a variety of skin disorders as well as some of the side effects seen in cancer patients treated with Hh pathway antagonists.

 

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