Professor, Molecular Biosciences; Judd A. and Marjorie Weinberg College of Arts and Sciences
Cancer Cell Biology
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The Holmgren laboratory studies pattern formation during animal development, focusing on the Hedgehog (Hh) signal transduction pathway and its role in patterning Drosophila segments and imaginal discs. This pathway is conserved in vertebrates and used in the development of numerous tissues and organs. Inappropriate activation of this pathway plays a central role in several important cancers. Dr. Holmgren identified the transcription factor Cubitus interruptus (Ci) as the primary target of Hh signaling in Drosophila. The laboratory is now trying to understand how the Hedgehog signaling pathway regulates different aspects of Ci function. A large scale RNAi suppressor/enhancer screen has been performed in a sensitized genetic background and identified a number of new components in the Hh pathway. The functions of these components are now being characterized. Recently, the Holmgren laboratory has established a collaboration with Dr. Matouschek to study the proteolytic processing of Ci and its mammalian homologues, the GLI proteins, by the proteasome. The Holmgren lab has also initiated a collaboration with Dr. Meade to generate a Co(III) Schiff base DNA conjugate to specifically inhibit the Ci/GLI transcription factors. These compounds will be tested in a model system for basal cell carcinoma.