Gender	Female
E-mail	patrizia.casaccia@mssm.edu
Education and Training	Ph.D., SUNY-HSCB
	M.D., Policlinico A. Gemelli
	Internship and Fellowship, Policlinico A. Gemelli
	Post-Doctoral Fellowship, Cornell Weill Medical Center
	Post-doctoral Research Associate, Skirball Institute for Biomolecular Medicine at NYU

Languages:
English
Spanish
Italian

Research Interests:
Epigenetic control of progenitor differentiation in development and diseases of the central nervous system
Myelin repair
Mechanism of axonal damage
Neural stem cells: mechanisms of proliferation and tumorigenesis

Approaches:
Genome-wide studies
Proteomics
ChIP
Confocal Analysis
In vivo imaging
Mouse models
Primary cultures from rodent brains
Human brain studies

Visit Dr. Patrizia Casaccia's Laboratory of Epigenetics in Demyelinating Disorders for more information.

Education and Training	Ph.D., SUNY-HSCB
	M.D., Policlinico A. Gemelli
	Internship and Fellowship, Policlinico A. Gemelli
	Post-Doctoral Fellowship, Cornell Weill Medical Center
	Post-doctoral Research Associate, Skirball Institute for Biomolecular Medicine at NYU

Research Interests
Epigenetic control of oligodendrocyte differentiation in development and disease
Myelin repair in demyelinating disorders
Mechanism of axonal damage in Multiple Sclerosis and demyelinating conditions
Neural stem cells: mechanisms of proliferation and differentiation. Implications for brain tumors

Project #1: Epigenetic Regulation of Progenitor Differentiation in the Developing and in the Aging Brain

Oligodendrocytes are the myelin-forming cells of the CNS and are essential for proper functioning of neural circuits. These cells are damaged by a wide variety of stimuli, ranging from prematurity in babies to ischemic or immunological attacks in adult brains. Using mouse and rat models, chromatin immunoprecipitation, proteomics, and genome-wide screens we are defining the mechanisms responsible for the differentiation of multipotential progenitors and neural stem cells into myelin-forming cells.  The goal of these studies is to understand how myelin-forming cells are generated during normal development in order to better understand mechanisms of de-regulated differentiation (i.e. cancer) and to design therapies for repairing aberrant or defective formation of oligodendrocytes in children (i.e. Canavan disease, etc.) and demyelination caused by stroke, inflammatory demyelination, spinal cord injury or trauma, in the adult brain.

Project #2: Molecular Mechanisms of Repair of Demyelinated Lesions

Multiple sclerosis is a disease characterized by clinical symptoms that are consequent to myelin damage.  Recovery of function can be obtained only after progenitors differentiate into myelinating oligodendrocytes and form new myelin.  We previously defined the critical role played by molecules called "histone deacetylases" (i.e. HDACs) in myelin formation during development and showed that administration of pharmacological inhibitors of HDAC to developing rats or fish inhibited developmental myelination. We have recently extended our work to the investigation of repair of damaged myelin in the adult brain. Using chromatin immunoprecipitation and confocal analysis of brain slices, we are characterizing the response of adult progenitors to toxic demyelination of white matter tracts in the mouse brain and spinal cord. We have also started to define whether similar changes occur in human derived cells. The long-term objective is to find molecular targets that are cell-specific and that can be used for the design of therapies directed towards promoting repair.

Project #3: Mechanisms of Regulation of Adult Neural Stem Cell

Although stem cell therapy has been proposed for repair, still relatively little is known about the behavior of these cells in the adult injured CNS. Our laboratory is interested in defining  the role of  p27Kip1 and p53, two crucial cell cycle regulators often mutated in brain tumors (i.e. glioblastomas).  Based on the results of proteomic and gene profiling studies, and transgenic mouse models, we are investigating molecular mechanisms integrating these two cell cycle genes within downstream signaling networks that modulate lineage determination and survival. The results of these studies will likely extend our current knowledge on the mechanisms of cell division and neoplastic transformation of adult SVZ cells. In addition, by addressing novel and unexplored roles for p27Kip and p53 as part of transcriptional networks and signaling pathways, they will also significantly impact several other fields, including developmental neurobiology and clinical neurobiology.

Visit Dr. Patrizia Casaccia's Laboratory of Epigenetics in Demyelinating Disorders for more information.

Shen S, Sandoval J, Swiss VA, Li J, Dupree J, Franklin RJ, Casaccia-Bonnefil P. Age-dependent epigenetic control of differentiation inhibitors is critical for remyelination efficiency (News and Views and Highlights in Nature Neuroscience Reviews). Nature Neurosci 2008;.

Li J, Ghiani CA, Kim JY, Liu A, Sandoval J, deVellis J, Casaccia-Bonnefil P. Inhibition of p53 transcriptional activity: a potential target for future development of therapeutic strategies for primary demyelination. J. Neurosci 2008; 28(24): 6118-6127.

He Y, Dupree J, Wang J, Sandoval J, Li J, Liu H, Shi Y, Nave KA, Casaccia-Bonnefil P. The transcription factor Yin Yang1 is essential for oligodendrocyte progenitor differentiation. Neuron 2007; 55(2): 217-230.

Liu A, Han R, Li J, Sun D, Ouyang M, Plummer M, Casaccia-Bonnefil P. The glial or neuronal fate choice of oligodendrocyte progenitors is modulated by their ability to acquire an epigenetic memory (COVER and Highlights in Nature Neuroscience Reviews). J. Neurosci 2007; 27(27): 7339-7343.

Mastronardi FG, Wood DD, Mei J, Raijmakers R, Tseveleki V, Dosch HM, Probert L, Casaccia-Bonnefil P, Moscarello MA. Increased citrullination of histone H3 in multiple sclerosis brain and animal models of demyelination: a role for tumor necrosis factor-induced peptidylarginine deiminase 4 translocation. J Neurosci 2006; 44: 11387-11396.

Liu A, Li J, Marin-Husstege M, Kageyama R, Fan Y, Gelinas C, Casaccia-Bonnefil P. A molecular insight of Hes5-dependent inhibition of myelin gene expression: old partners and new players . EMBO J 2006; 25(20): 4833-4842.

Cunliffe V, Casaccia-Bonnefil P. Histone deacetylase 1 is essential for oligodendrocyte specification in the zebrafish CNS. Mech. Devel 2006; 123: 24-30.

Gil-Perotin S, Verdugo JM, Li J, Marin-Husstege M, Soriano-Navarro M, Zindy F, Roussel M, Casaccia-Bonnefil P. Loss of p53 induces changes in the behaviour of subventricular zone cells: implications for the genesis of glial tumors. J. Neurosci 2006; 26: 1107-1116.

Shen S, Li J, Casaccia-Bonnefil P. Histone modifications affect timing of oligodendrocyte progenitor differentiation in the developing rat brain. J. Cell Biol 2005; 169: 577-589.

Liu A, Stadelman C, Mastronardi F, Moscarello M, Sobel A, Casaccia-Bonnefil P. Expression of stathmin, a developmentally controlled cytoskeleton regulating molecule, in demyelinating disorders. J. Neurosci 2005; 25: 737-747.