Areas of Research: Cancer Biology; utilizing in vivo models to study signaling pathways altered in advanced thyroid cancer; development of novel therapeutic strategies based on the tumor molecular landscape; tumor/microenvironment interaction
The thyroid gland is a central endocrine hub where a complex array of signals in the form of hormones and growth factors are integrated to govern thyroid growth and activity. As such, the thyroid represents an ideal model system to study the interaction between these signals in normal homeostasis as well as in the context of neoplastic transformation.
The main focus of my laboratory is the PI3K signaling pathway, and the role it plays in thyroid physiology and pathophysiology. We utilize genetically engineered mouse models to identify and deconstruct the signaling cascades controlled by PI3K and altered during early neoplastic transformation, to understand through which signaling nodes the PI3K cascade intersects with other growth-promoting pathways, and to design and test in vivo innovative, rationally designed therapeutic approaches for advanced thyroid cancer.
- Champa, D., Russo, M.A., Liao, X-H., Refetoff, S., Ghossein, R.A., and Di Cristofano, A. Obatoclax overcomes resistance to cell death in aggressive thyroid carcinomas by countering Bcl2a1 and Mcl1 overexpression. Endocr. Relat. Cancer, 21:755-767, 2014.
- Antico Arciuch V.G., Russo, M.A., Kang, K.S, and Di Cristofano, A. Inhibition of AMPK and Krebs cycle gene expression drives metabolic remodeling of Pten-deficient preneoplastic thyroid cells. Cancer Res., 73: 5459-5472, 2013.
- Russo, M.A., Kang, K.S., and Di Cristofano, A. The PLK1 inhibitor GSK461364A is effective in poorly differentiated and anaplastic thyroid carcinoma cells, independent of the nature of their driver mutations. Thyroid, 23:1284-1293, 2013.
- Antico Arciuch V.G., Russo, M.A., Dima, M., Kang, K.S., Dasrath, F., Liao, X-H., Refetoff, S., Montagna, C., and Di Cristofano, A. Thyrocyte-specific inactivation of p53 and Pten results in anaplastic thyroid carcinomas faithfully recapitulating human tumors. Oncotarget, 2:1109-1126, 2011.
- Dima, M., Miller, K.A., Antico-Arciuch V.G., and Di Cristofano, A. Establishment and characterization of cell lines from a novel mouse model of poorly differentiated thyroid carcinoma: powerful tools for basic and preclinical research. Thyroid, 21:1001-1007, 2011.
- Antico-Arciuch VG, Dima, M., Liao, X-H., Refetoff, S., and Di Cristofano, A. Cross-talk between PI3K and estrogen in the mouse thyroid predisposes to the development of follicular carcinomas with a higher incidence in females. Oncogene, 29:5678-5686, 2010.
- Miller, K., Yeager, N., Baker, K., Liao, X-H., Refetoff, S., and Di Cristofano, A. Oncogenic Kras Requires Simultaneous PI3K Signaling to Induce ERK Activation and Transform Thyroid Epithelial Cells in Vivo. Cancer Res., 69:3689-3694, 2009.
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