Laboratory of Signal Transduction

Head: Tomasz WILANOWSKI

Staff: Agnieszka Kikulska (PhD student), Michał Mlącki (PhD student), Magdalena Pawlak (PhD student)

Research profile:

Signal transduction in mammalian cells; signaling pathways; planar cell polarity pathway; role of the Grainyhead-like (GRHL) transcription factors in signal transduction; regulation of gene expression by the GRHL transcription factors; regulation of the activity of GRHL proteins; analysis of phenotypes of mouse strains carrying mutations in the Grhl genes; neural tube closure; wound healing; mechanisms of GRHL function in health and disease.

Methods:

• PCR
• quantitative PCR
• DNA sequencing
• histology
• immunohistochemistry
• immunofluorescence
• Western blotting
• chromatin immunoprecipitation
• electrophoretic mobility shift assays
• transfection studies
• phenotypic analyses

Current research activities:

• functions of the GRHL1 gene in human disease
• analysis of the phenotype of Grhl1 mutant mice
• mechanisms of regulation of the activity of GRHL1 protein
• regulation of gene expression by the GRHL1 transcription factor
• role of the Grainyhead-like factors in neural tube closure
• involvement of the planar cell polarity pathway in wound healing

Selected publications:

Dworkin S, Darido C, Georgy SR, Wilanowski T, Srivastava S, Ellett F, Pase L, Han Y, Meng A, Heath JK, Lieschke GJ, Jane SM (2012) Midbrain-hindbrain boundary patterning and morphogenesis are regulated by diverse Grainy head-like 2-dependent pathways. Development 139: 525-536

Darido C, Georgy SR, Wilanowski T, Dworkin S, Auden A, Zhao Q, Rank G, Srivastava S, Finlay MJ, Papenfuss AT, Pandolfi PP, Pearson RB, Jane SM (2011) Targeting of the tumor suppressor GRHL3 by a miR-21-dependent proto-oncogenic network results in PTEN loss and tumorigenesis. Cancer Cell 20: 635-648

Boglev Y, Wilanowski T, Caddy J, Parekh V, Auden A, Darido C, Hislop NR, Cangkrama M, Ting SB, Jane SM (2011) The unique and cooperative roles of the Grainy head-like transcription factors in epidermal development reflect unexpected target gene specificity. Dev Biol 349: 512-522

Caddy J, Wilanowski T, Darido C, Dworkin S, Ting SB, Zhao Q, Rank G, Auden A, Srivastava S, Papenfuss TA, Murdoch JN, Humbert PO, Parekh V, Boulos N, Weber T, Zuo J, Cunningham JM, Jane SM (2010) Epidermal wound repair is regulated by the planar cell polarity signaling pathway. Dev Cell 19: 138-147

Wilanowski T, Caddy J, Ting SB, Hislop NR, Cerruti L, Auden A, Zhao L-L, Asquith S, Ellis S, Sinclair R, Cunningham JM, Jane SM (2008) Perturbed desmosomal cadherin expression in Grainy head-like 1-null mice. EMBO J. 27: 886-897