Rosemary Akhurst, PhD
Rosemary Akhurst, PhD
The TGF-beta signaling pathway and cancer stem cells
Components of the TGF-β signaling pathway are essential in stem cell maintenance and lineage specification of both embryonic, adult and cancer stem cells. The Akhurst lab is undertaking a functional dissection of genetic loci, Tgfbm1, Tgfbm2 and Tgfbm3, that modify biological responses to TGF-β1 during angiogenesis and vascular remodeling. We hypothesize that Tgfbm loci regulate the ability of haematopoietic stem and endothelial progenitor cells to mobilize from the bone marrow and a) to home to sites of vascular injury during tissue repair, and b) to home to the pre-metastatic niche during tumorigenesis.
Selected Publications
*Oft M, Akhurst RJ, and Balmain A. (2002) Metastasis is driven by sequential elevation of H-ras and Smad2 levels. Nature Cell Biology 4:487-494.
Ewan KB, Ravani SA, Shyamala G, Tang Y, Akhurst RJ, Wakefield L, and Barcellos-Hoss MH. (2002) Latent Transforming Growth Factor-beta Activation in Mammary Gland: Regulation by Ovarian Hormones Affects Ductal and Alveolar Proliferation. Am. J. Pathol. 160:2081-2093.
Ewan KB, Henshall-Powell RL, Ravani SA, Parjares MJ, Arteaga C, Warters R, Akhurst RJ, and Barcellos-Hoff MH. (2002) Depletion of Transforming Growth Factor-$ð 1 Blocks Radiation-Induced Apoptosis and p53 Response Cancer. Res 62:5627-31.
*Tang Y, McKinnon ML, Leong LM, Rusholme SAB, Wang S, andAkhurst RJ. (2003) Genetic modifiers interact with maternal determinants in vascular development of Tgfb1-/- mice Human Molecular Genetics 12:1579-1679.
Chan CK, Pham LN, Chinn C, Spee C, Ryan SJ, Akhurst RJ, and Hinton DR. (2004) Mouse Strain-dependent Heterogeneity of Resting Limbal Vasculature. Invest Ophthalmol Vis Sci 45(2):441-447.
Tang Y, Lee KS, Yang HT, Logan DW, Wang S, McKinnon ML, Holt LJ, Condie A, Luu MT, and Akhurst RJ. (2005) Epistatic interactions between modifier genes confer strain-specific redundancy for Tgfb1 in developmental angiogenesis. Genomics 85:60-70.
Poon E, Clermont F, Firpo MT, and Akhurst RJ. (2006) TGF² inhibition of yolk sac-like differentiation of human embryonic stem cell-derived embryoid bodies illustrates differences between early mouse and human development. J. Cell Sci. 119:759-68.
Lacher MD, Tiirikainen MI, Saunier EF, Christian C, Anders M, Oft M, Balmain A, Akhurst RJ, and Korn WM. (2006) TGF² Receptor Inhibition Enhances Adenoviral Infectivity of Carcinoma Cells Via Up-regulation of CAR in Conjunction with Reversal of Epithelial- Mesenchymal-Transition. Cancer Res. 66:1648-57.
*Mao JH, Saunier EF, de Koning J, McKinnon MM, Higgins MN, Nicklas K, Yang HT, Balmain A, and Akhurst RJ. (2006) Genetic variants of Tgfb1 act as context-dependent modifiers of mouse skin tumor susceptibility. Proc. Natl. Acad. Sci (USA) 103(21):8125-30.
