Since more than a decade we are studying the dynamics of adult neurogenesis in vivo and in vitro, in the two neurogenic brain niches that continue to generate new neurons during adulthood, i.e., the dentate gyrus of the hippocampus and the subventricular zone, and also in the postnatal cerebellum, which shows a transient but strong process of neurogenesis after birth. The continued production of new neurons during adulthood  in the hippocampus plays an important role in improving the efficiency of episodic and associative memory, as shown by several laboratories including ours. The cerebellum, moreover, has an important role not only in motor coordination but also in the control of affective processes.

In these studies on neurogenesis we are using mouse models generated by us, with genetic alterations of the processes of proliferation and differentiation of neural stem cells.  Our efforts are thus aimed to elucidate at the cellular and genetic levels the processes of self-renewal and maturation as well as the functional aspects (memory) of stem cells and neural progenitors in the hippocampus, the subventricular zone and also in the cerebellum. We are focusing in particular on the effects of different neurogenic stimuli on the ability of stem cells to replicate and differentiate; we are experimentally evaluating the interplay between the genetic controls of cell cycle and differentiation, as separate regulators of the maturation of stem cells in adult neurons.
We have studied during the last years also the process of maturation of the stem cells of the skeletal muscle (satellite cells), identifying a gene (IFRD1) that stimulates their regeneration.

From these studies we are developing also therapeutic applications, to cure diseases connected to the developmental pathologies of the neural and muscle stem cells, thanks to the support of grants to projects of Felice Tirone from the Fondazione Giovanni Celeghin and, in the past, from the Italian Association for Cancer Research (AIRC) and from Telethon:

a) Preclinical studies of gene therapy in animal models spontaneously developing the cerebellum tumor (medulloblastoma). These studies are aimed to inhibit the medulloblastoma by using tumor-suppressor genes that we have identified as regulators of the development of the cerebellar neuron precursors (Tis21, Cxcl3).
b) Preclinical studies of gene therapy in animal models of muscular dystrophy, aimed to stimulate the regeneration of muscle stem cells (satellite cells) by the gene IFRD1, and thus to counteract  muscular dystrophy.

Some publications of the laboratory on these issues:

Micheli L, D'Andrea G, Ceccarelli M, Ferri A, Scardigli R, Tirone F. (2019) p16Ink4a  Prevents the Activation of Aged Quiescent Dentate Gyrus Stem Cells by Physical Exercise. Front Cell Neurosci. 13:10. doi: 10.3389/fncel.2019.00010.

Micheli L, Ceccarelli M, D'Andrea G, Tirone F. (2018) Depression and adult neurogenesis: Positive effects of the antidepressant fluoxetine and of physical exercise. Brain Res Bull. 143:181-193. doi: 10.1016/j.brainresbull.2018.09.002.

Micheli L, Ceccarelli M, D'Andrea G, Costanzi M, Giacovazzo G, Coccurello R, Caruso C, Tirone F. (2018) Fluoxetine or Sox2 reactivate proliferation-defective stem and progenitor cells of the adult and aged dentate gyrus. Neuropharmacology 141:316-330. doi: 10.1016/j.neuropharm.2018.08.023.

Micheli L, Ceccarelli M, Gioia R, D'Andrea G, Farioli-Vecchioli S, Costanzi M, Saraulli D, Cestari V, Tirone F. (2017) Terminal Differentiation of Adult Hippocampal Progenitor Cells Is a Step Functionally Dissociable from Proliferation and Is Controlled by Tis21, Id3 and NeuroD2. Front Cell Neurosci. 2017 11:186. doi: 10.3389/fncel.2017.00186.

Mastrorilli V, Scopa C, Saraulli D, Costanzi M, Scardigli R, Rouault JP, Farioli-Vecchioli S, Tirone F. (2017) Physical exercise rescues defective neural stem cells and neurogenesis in the adult subventricular zone of Btg1 knockout mice. Brain Struct Funct. 222(6):2855-2876. doi: 10.1007/s00429-017-1376-4.

Ceccarelli M, Micheli L, Tirone F. (2016) Suppression of Medulloblastoma Lesions by Forced Migration of Preneoplastic Precursor Cells with Intracerebellar Administration of the Chemokine Cxcl3. Front Pharmacol. 7:484. doi: 10.3389/fphar.2016.00484.

Micheli L, D'Andrea G, Leonardi L, Tirone F. (2017) HDAC1, HDAC4, and HDAC9 Bind to PC3/Tis21/Btg2 and Are Required for Its Inhibition of Cell Cycle Progression and Cyclin D1 Expression. J Cell Physiol. 232(7):1696-1707. doi: 10.1002/jcp.25467.

Ceccarelli M, Micheli L, D'Andrea G, De Bardi M, Scheijen B, Ciotti M, Leonardi L, Luvisetto S, Tirone F. (2015) Altered cerebellum development and impaired motor coordination in mice lacking the Btg1 gene: Involvement of cyclin D1. Dev Biol. 408(1):109-125. doi: 10.1016/j.ydbio.2015.10.007.

Tirone F, Farioli-Vecchioli S, Micheli L, Ceccarelli M, Leonardi L. 2013. Genetic control of adult neurogenesis: interplay of differentiation, proliferation and survival modulates new neurons function, and memory circuits. Front Cell Neurosci. 7:59.

Farioli-Vecchioli S, Mattera A, Micheli L, Ceccarelli M, Leonardi L, Saraulli D, Costanzi M, Cestari V, Rouault J-P, Tirone F. (2014) Running rescues defective adult neurogenesis by shortening the length of the cell cycle of neural stem and progenitor cells. Stem Cells 32:1968-1982.

Farioli-Vecchioli S, Ceccarelli M, Saraulli D, Micheli L, Cannas S, D'Alessandro F, Scardigli R, Leonardi L, Cinà I, Costanzi M, Mattera A, Cestari V and Tirone F (2014). Tis21 is required for adult neurogenesis in the subventricular zone and for olfactory behavior regulating cyclins, BMP4, Hes1/5 and Ids. Front. Cell. Neurosci. 8:98.

Micheli M, Leonardi L, Conti F, Maresca G, Colazingari S, Mattei E, Lira SA, Farioli-Vecchioli S, Caruso M, Tirone F. (2011). PC4/Tis7/IFRD1 stimulates skeletal muscle regeneration and is involved in myoblast differentiation as a regulator of MyoD and NF-kB. J Biol Chem. 286:5691-5707.