Prof. Julio Aguirre-Ghiso, Icahn School of Medicine at Mount Sinai, Ticsh Cancer Institute, New York, USA

Host: Johanna Ivaska (johanna.ivaska@utu.fi)

Despite complete primary tumour removal and seemingly successful therapeutic intervention, many cancer patients go on to develop devastating and incurable metastases. This is due to the presence of long-lived disseminated tumour cells that remain hidden and inactive (dormant) during the therapeutic window.

The focus of Prof. Aguirre-Ghiso’s laboratory (http://labs.icahn.mssm.edu/aguirre-ghisolab/research/) is to understand the biology of dormant disseminated tumour cells, and to unravel the pathways that lead to their reactivation. By combining mechanisms of basic stress and mitogenic signalling, adult stem cell and microenvironmental biology and intravital imaging, his team has discovered that reciprocal crosstalk between dormant tumour cells and the microenvironment regulates the inter-conversion between dormancy and proliferation through an epigenetic network. Ultimately, his group aims to develop strategies that prevent patient relapse by targeting dormant tumour cell reactivation.

Selected publications

Linde N, Casanova-Acebes M, Sosa MS, Mortha A, Rahman A, Farias EF, Harper K, Tardio E, Reyes Torres I, Jones J, Condeelis J, Merad M, and Aguirre-Ghiso JA.
Macrophages orchestrate breast cancer early dissemination and metastasis. Nature Communications 9, 21(2018) doi:10.1038/s41467-017-02481-5.

Entenberg D, Pastoriza JM, Oktay MH, Voiculescu S, Wang Y, Sosa MS, Aguirre-Ghiso JA, Condeelis J. Time-lapsed, large-volume, high-resolution intravital imaging for tissue-wide analysis of single cell dynamics, Methods, Volume 128, 1 September 2017, Pages 65-77, ISSN 1046-2023, https://doi.org/10.1016/j.ymeth.2017.07.019

Fluegen G, Avivar-Valderas A, Wang Y, Padgen M, Williams JK, Nobre AR, Calvo V, Cheun JF, Bravo Cordero J, Entenberg D, Castracane J , Verkhusha V, Keely PJ, Condeelis J and Aguirre-Ghiso, JA. Phenotypic heterogeneity of disseminated tumor cells is preset by primary tumor hypoxic microenvironments. Nature Cell Biology (2017) doi:10.1038/ncb3465. 

Harper KL, Sosa MS, Entenberg D, Hosseini H, Cheung JF, Nobre R, Avivar-Valderas A, Nagi C, Girnius N, Davis RJ, Farias EF, Condeelis J, Klein CA, Aguirre-Ghiso JA. Mechanism of early dissemination and metastasis in HER2+ mammary cancer. Nature. (2016) Dec 14. doi: 10.1038/nature20609.

Hosseini, H,  Obradovic M, Harper K,  Sosa MS, Nanduri LK, Werno C, Hoffman, M, Ehrl C, Maneck M, Patwary N, Haunschild G, Reimelt C, Weeber F, Hartkopf A, Taran FA, Brucker SY, Fehm T, Meister G, Aguirre-Ghiso JA, Klein CA. Early dissemination seeds metastasis in breast cancer. Nature. (2016) Dec 14. doi: 10.1038/nature20785.

Cackowski F, Eber MR, Rhee J, Decker A, Yumoto K, Berry JE, Lee E, Shiozawa Y, Jung Y, Aguirre-Ghiso JA, Taichman RS. Mer Tyrosine Kinase Regulates Disseminated Prostate Cancer Cellular Dormancy. J Cell Biochem. (2016) Oct 18. doi: 10.1002/jcb.25768.

Li M, Pathak RR, Lopez-Rivera E, Friedman SL, Aguirre-Ghiso JA, Sikora AG. The In Ovo Chick Chorioallantoic Membrane (CAM) Assay as an Efficient Xenograft Model of Hepatocellular Carcinoma. J Vis Exp. (2015) Oct 9;(104). doi: 10.3791/52411.

Alsadeq A, Strube S, Krause S, Carlet M, Jeremias I, Vokuhl C, Loges S, Aguirre-Ghiso JA, Trauzold A, Cario G, Stanulla M, Schrappe M, Schewe DM. Effects of p38α/β inhibition on acute lymphoblastic leukemia proliferation and survival in vivo. Leukemia. (2015) Jun 24. doi: 10.1038/leu.2015.153.

 Adomako A, Calvo V, Biran N, Osman K, Chari A, Paton JC, Paton AW, Moore K, Schewe DM, Aguirre-Ghiso JA. Identification of markers that functionally define a quiescent multiple myeloma cell sub-population surviving bortezomib treatment. BMC Cancer. (2015) May 30;15:444. doi: 10.1186/s12885-015-1460-1.

Hasegawa D, Calvo V, Avivar-Valderas A, Lade A, Chou HI, Lee YA, Farias EF, Aguirre-Ghiso JA, Friedman SL. Epithelial Xbp1 is Required for Cellular Proliferation and Differentiation During Mammary Gland Development. Mol Cell Biol. 2015 Feb 23. pii: MCB.00136-15.

 Sosa MS, Parikh F, Maia AG, Estrada Y, Bosch A, Bragado P, Ekpin E, George A, Zheng Y, Lam HM, Morrissey C, Chung CY, Farias EF, Bernstein E, Aguirre-Ghiso JA. NR2F1 controls tumour cell dormancy via SOX9- and RARβ-driven quiescence programmes. Nat Commun. 2015 Jan 30;6:6170. doi: 10.1038/ncomms7170.

Bragado P., Estrada Y., Parikh F., Krause S., Capobianco C., Farina H.G., Schewe D.M., and Julio A. Aguirre-Ghiso JA. TGFβ2 dictates disseminated tumour cell fate in target organs through TGFβ-RIII and p38α/β signalling. Nat. Cell. Bio. (2013). Nov;15(11):1351-61. doi: 10.1038/ncb2861.