Neuroscience
Neural stem cell biology
Neural stem cells have been identified in the central nervous system (CNS) of several different species, including humans. Their physiological function consists in the replacement of physiologically lost neurons within restricted CNS areas such as the olfactory bulbs and the hippocampus. These cells are thought to be etiologically involved in the pathogenesis of several genetic diseases involving the CNS. At the same time, they are considered the cell substrate, which, upon mutation, can transform and give rise to cerebral tumors.
Research activity
The research activity of this group is currently focused on the study of the basic biology of neural stem cells, in relation with the pathogenesis of tuberous sclerosis complex, a genetic disease severely affecting the CNS, and the development of highly malignant brain tumors such as glioblastoma multiforme and medulloblastoma. To this end, neural stem cells of different origin are compared, both from a functional and molecular standpoint, to cancer stem cells and/or to neural stem cells bearing specific mutations, by exploiting in vitro and in vivo models joined with state-of- the-art molecular technologies.
Gagliardi F., Narayanan A., Gallotti A.L., Pieri V., Mazzoleni S., Cominelli M., Rezzola S., Corsini M., Brugnara G., Altabella L., Politi L.S., Bacigaluppi M., Falini A., Castellano A., Ronca R., Poliani P.L., Mortini P., Galli R. Enhanced SPARCL1 Expression in Cancer Stem Cells Improves Preclinical Modeling of Glioblastoma by Promoting Both Tumor In ltration and Angiogenesis. Neurobiol Dis, 104705 2019 Dec 9
Narayanan A., Gagliardi F., Gallotti A.L., Mazzoleni S., Cominelli M., Fagnocchi L., Pala M., Piras I.S., Zordan P., Moretta N., Tratta E., Brugnara G., Altabella L., Bozzuto G., Gorombei P., Molinari A., Padua R.A., Bulfone A., Politi L.S., Falini A., Castellano A., Mortini P., Zippo A., Poliani P.L., and Galli R. The proneural gene ASCL1 governs the transcriptional subgroup a liation in glioblastoma stem cells by directly repressing the mesenchymal gene NDRG1. Cell Death & Differentiation, 2019, 26 (9), 1813-1831.
Zordan P, Cominelli M, Cascino F, Tratta E, Poliani PL and Galli R. Tuberous sclerosis complex-associated CNS abnormalities depend on hyperactivation of mTORC1 and Akt. Journal of Clinical Investigation, 2018.
Politi L, Brugnara G, Castellano A, Cadioli M, Altabella L, Peviani M, Mazzoleni S, Falini A, Galli R. T1-Weighted Dynamic Contrast- Enhanced MRI is a Non-Invasive Marker of Epidermal Growth Factor Receptor vIII Status in Cancer Stem Cell-derived Experimental Glioblastomas. American Journal of Neuroradiology 2016;37(6):E49-51 .
Cominelli M, Grisanti S, Mazzoleni S, Branca C, Buttolo L, Furlan D, Liserre B, Bonetti MF, Medicina D, Pellegrini V, Buglione M, Liserre R, Pellegatta S, Finocchiaro G, Dalerba P, Facchetti F, Pizzi M, Galli R and Poliani PL. EGFR Amplified and overexpressing glioblastomas are associated with better response to Adjuvant Metronomic Temozolomide. Journal of the National Cancer Institute 2015 Mar 3;107(5).
Hemmesi K, Squadrito ML, Mestdagh P, Conti V, Cominelli M, Piras IS, Sergi Sergi L, Piccinin S, Maestro R, Poliani PL, Speleman F, De Palma M, Galli R. miR-135a inhibits cancer stem cell-driven medulloblastoma development by directly repressing Arhgef6 expression. Stem Cells 2015;33(5):1377-89.
Magri L, Cominelli M, Cambiaghi M, Cursi M, Leocani L, Minicucci F, Poliani PL, Galli R. Timing of mTOR activation affects tuberous sclerosis complex neuropathology in mouse models. Disease Models & Mechanisms 2013 Sep;6(5):1185-97.
Mazzoleni S, Jachetti E, Morosini S, Grioni M, Piras IS, Pala M, Bulfone A, Freschi M, Bellone M, Galli R. Gene signatures distinguish stage-specific prostate cancer stem cells from transgenic adenocarcinoma of the mouse prostate (TRAMP) lesions and predict the malignancy of human tumors. Stem Cells Translational Medicine 2013 Sep;2(9):678-89.
Corno D, Pala M, Cominelli M, Cipelletti B, Leto K, Croci L, Barili V, Brandalise F, Melzi R, Di Gregorio A, Sergi Sergi L, Politi LS, Piemonti L, Bulfone A, Rossi P, Rossi F, Consalez GG, Poliani PL, Galli R. Gene signatures associated with mouse postnatal hindbrain neural stem cells and medulloblastoma cancer stem cells identify novel molecular mediators and predict human MB molecular classification. Cancer Discovery 2012;2: 554-568.
Magri L, Cambiaghi M, Cominelli M, Alfaro-Cervello C, Cursi M, Pala M, Bulfone A, Garcia-Verdugo JM, Leocani L, Minicucci F, Poliani PL, Galli R. Sustained activation of mTOR pathway in embryonic neural stem cells leads to development of Tuberous Sclerosis Complex-associated lesions. Cell Stem Cell 2011 Nov 4;9(5):447-62.
Mazzoleni S, Politi LS, Pala M, Cominelli M, Franzin A, Sergi Sergi L, Falini A, De Palma M, Bulfone A, Poliani PL and Galli R. EGFR expression identifies functionally and molecularly distinct tumor-initiating cells in human glioblastoma multiforme and it is required for gliomagenesis. Cancer Res. 2010;70(19):7500- 13.
Di Tomaso T , Mazzoleni S, Wang E, Sovena G, Clavenna D, Franzin A, Mortini P, Ferrone S, Doglioni C, Marincola F, Galli R, Parmiani G, Maccalli C. Immuno-biological characterization of cancer stem cells isolated from glioblastoma patients. Clin. Cancer Res. 2010;16(3): 800-13.
Galli R, Binda E, Orfanelli U, Cipelletti B, Gritti A, De Vitis S, Fiocco R, Foroni C, DiMeco F, Vescovi A. Isolation and characterization of tumorigenic, stem-like neural precursors from human glioblastoma. Cancer Research 2004 Oct 1;64(19):7011-21.
