Photo of Patrizia Casaccia

Patrizia Casaccia

  • PROFESSOR Neuroscience
  • PROFESSOR Genetics and Genomic Sciences
  • PROFESSOR Neurology
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Education

  • Skirball Institute for Biomolecular Medicine at NYU

  • Cornell Weill Medical Center

  • Policlinico A. Gemelli
    Neurology

  • Ph.D., SUNY-HSCB
    Neurobiology

  • M.D., Policlinico A. Gemelli
    Medicine

Biography

    Dr. Patrizia Casaccia is Professor of Neuroscience, Genetics and Genomics; and Neurology. Dr. Casaccia is the Chief of the Center of Excellence for Myelin Repair at the Friedman Brain Institute at Mount Sinai School of Medicine.

    She received her medical degree with Honors from the University of Rome, and a PhD degree in Neurobiology from State University of New York (SUNY) Health and Science Center Brooklyn.  She then trained at Cornell Weill Medical Center in New York and at the Skirball Institute for Molecular Medicine at NYU.

    Dr. Casaccia’s work adopts molecular and cellular techniques to find new therapies for multiple sclerosis. Her work includes translational research in regenerative and personalized medicine.  The laboratory focuses on myelin repair with a special emphasis on the effect of aging and gender differences. In addition, her research addresses the mechanism of neuronal damage in patients with MS leading to novel screening for the discovery of new therapies to protect the neurons and replace damaged myelin.

    The new methodologies leading to personalized medicine include the generation of neural stem cells from patients' skin, and the analysis of DNA and RNA from the blood of multiple sclerosis patients.  Her work is funded by grants from the National Institute for Neurological Disorders and Stroke and by the National Multiple Sclerosis Society.

    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 of Neural Repair for more information.

Research

Dr. Casaccia’s  lab  adopts state-of-the art molecular and cellular techniques to define key questions in developmental neurobiology and find new therapies for Multiple Sclerosis and several other disorders characterized by lost or damaged myelin (including premature babies, genetic disorders, traumatic brain injury).


Four Research Areas:

1. Epigenetic Regulation of Gene Expression

2. Developmental Neurobiology

3. Translational Research (Drug Discovery for Myelin Repair and preservation of Axonal function) 

4. Personalized Medicine of Demyelinating Disorders

 

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 (i.e. Multiple Sclerosis). 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 #1: Epigenetic Regulation of Gene Expression


Even though they all have the same DNA, each cell type expresses a set of specific genes and retains a precise “MOLECULAR MEMORY” of cell identity. This area of research in the lab is aimed to answering the following questions:

- How do distinct cells acquire their UNIQUE identity within an organism? (How does an oligodendrocyte “know to make myelin” rather than producing digestive enzymes?)

- What are the mechanisms that allow stability and homeostasis?

- Does AGE, or disease alter the mechanism regulating cell identity ?



Project #2: Developmental Neurobiology

How does a progenitor decide to become an oligodendrocyte ? What happens to the nuclear architecture during this transition? What is the relationship between proliferation and differentiation? Are progenitors intrinsically “biased” towards a myelinating or non-myelinating phenotype? Can this bias be modulated by the environment?

Project #3. 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. Because the clinical course of demyelinating diseases results from a disequilibrium between damage and repair we are tackling the problem from both ends: reduce damage and enhance repair by developing new drugs.   In collaboration with the group of Chemical Epigenomics at Mount Sinai, we are screening newly synthesized pharmacological compounds in brain cells  from rodents and humans, for their ability to form new myelin. The most promising molecules are then tested in mice for the ability to enhance recovery from experimentally induced demyelination.

Project #4. Personalized Medicine of Demyelinating Disorders

The overall idea that we are testing, in collaboration with the Corinne Goldsmith Center for Multiple Sclerosis is that each patient has a unique “signature” which results from the interplay of genes, environment, gender and age.  We believe that this signature modulates the course of the disease and the response to therapy and can be identified by analyzing DNA and RNA from MS patients, by adopting molecular and cellular techniques.

For each patient we want to create a “personalized” disease-model in a dish, using the latest induced Pluripotent Stem Cell technology.

Once this model is established, hundreds of commercially available and newly synthesized pharmacological agents can be screened using robotic technology, to define novel personalized strategies that will decrease disability and enhance repair.



Publications

Magri L, Gacias M, Wu M, Swiss VA, Janssen WG, Casaccia P. c-Myc-dependent transcriptional regulation of cell cycle and nucleosomal histones during oligodendrocyte differentiation. Neuroscience 2014 Feb;.

Magri L, Swiss VA, Jablonska B, Lei L, Pedre X, Walsh M, Zhang W, Gallo V, Canoll P, Casaccia P. E2F1 coregulates cell cycle genes and chromatin components during the transition of oligodendrocyte progenitors from proliferation to differentiation. The Journal of neuroscience : the official journal of the Society for Neuroscience 2014 Jan; 34(4).

Huynh JL, Garg P, Thin TH, Yoo S, Dutta R, Trapp BD, Haroutunian V, Zhu J, Donovan MJ, Sharp AJ, Casaccia P. Epigenome-wide differences in pathology-free regions of multiple sclerosis-affected brains. Nature neuroscience 2014 Jan; 17(1).

Vidaurre OG, Haines JD, Katzsand I, Adula KP, Huynh JL, Sotirchos E, McGraw C, Zhang F, Varghese M, Pasinetti G, Zhang W, Inglese M, Haughey NJ, Calabresi PA, Gang W, Miller AE, Lublin FD, Casaccia P. Bioenergetic failure induced by lipids in the cerebrospinal fluid of Multiple Sclerosis patients.. Brain 2014;.

Dutta DJ, Zhang J, Zamee A, Asp L, Huynh JL, Mahase S, Argaw AT, Mitiku N, Mariani J, Casaccia P, Hayot F, Bottinger EP, Chester CW, John GR. Synergistic actions of Tgfβ ligands and Activin B promote oligodendrocyte development.. Development 2014;.

Gacias-Monserrat M, Gerona-Navarro G, Plotnikov AN, Zhang G, Zeng L, Kaur J, Moy G, Rusinova E, Rodriguez Y, Matikainen B, Vincek A, Joshua J, Casaccia P, Zhou M. Selective Chemical Modulation of Gene Transcription Favors OligodendrocyteLineage Progression. Chemistry Biology 2014;.

Huynh JL, Garg P, Thin TH, Yoo S, Dutta R, Trapp BD, Haroutunian V, Zhu J, Donovan MJ, Sharp AJ, Casaccia P. Epigenome-wide differences in pathology-free regions of multiple sclerosis-affected brains. Nature neuroscience 2014 Jan; 17(1).

Gacias M, Casaccia P. Promoting return of function in multiple sclerosis: An integrated approach. Multiple sclerosis and related disorders 2013 Oct; 2(4).

Wu M, Hernandez M, Shen S, Sabo JK, Kelkar D, Wang J, O'Leary R, Phillips GR, Cate HS, Casaccia P. Differential modulation of the oligodendrocyte transcriptome by sonic hedgehog and bone morphogenetic protein 4 via opposing effects on histone acetylation. The Journal of neuroscience : the official journal of the Society for Neuroscience 2012 May; 32(19).

Gacias M, Casaccia P. Promoting Return of Function in Multiple Sclerosis: an integrated approach. MS and Related Disorders 2013;.

Magri L, Swiss V, Jablonska B, Lei L, Pedre X, Walsh M, Zhang W, Gallo V, Canoll P, Casaccia P. E2F1 co-regulates cell cycle genes and chromatin components during the transition of oligodendrocyte progenitors from proliferation to differentiation. J. Neurosci 2013;.

Vidaurre OG, Liu J, Haines J, Sandoval J, Nowakowski R, Casaccia P. An integrated approach to design novel therapeutic interventions for demyelinating disorders. The European journal of neuroscience 2012 Jun; 35(12).

Huynh JL, Casaccia P. Epigenetic mechanisms in multiple sclerosis: implications for pathogenesis and treatment. Lancet neurology 2013 Feb; 12(2).

Liu J, Dietz K, DeLoyht JM, Pedre X, Kelkar D, Kaur J, Vialou V, Lobo MK, Dietz DM, Nestler EJ, Dupree J, Casaccia P. Impaired adult myelination in the prefrontal cortex of socially isolated mice. Nature neuroscience 2012 Dec; 15(12).

Bharadwaj R, Jiang Y, Mao W, Jakovcevski M, Dincer A, Krueger W, Garbett K, Whittle C, Tushir JS, Liu J, Sequeira A, Vawter MP, Gardner PD, Casaccia P, Rasmussen T, Bunney WE, Mirnics K, Futai K, Akbarian S. Conserved chromosome 2q31 conformations are associated with transcriptional regulation of GAD1 GABA synthesis enzyme and altered in prefrontal cortex of subjects with schizophrenia. The Journal of neuroscience : the official journal of the Society for Neuroscience 2013 Jul; 33(29).

Huynh JL, Casaccia P. Epigenetic mechanisms in multiple sclerosis: implications for pathogenesis and treatment. Lancet neurology 2013 Feb; 12(2).

Liu J, Dietz K, DeLoyht JM, Pedre X, Kelkar D, Kaur J, Vialou V, Lobo MK, Dietz DM, Nestler EJ, Dupree J, Casaccia P. Impaired adult myelination in the prefrontal cortex of socially isolated mice. Nature neuroscience 2012 Dec; 15(12).

Pedre X, Mastronardi F, Bruck W, López-Rodas G, Kuhlmann T, Casaccia P. Changed histone acetylation patterns in normal-appearing white matter and early multiple sclerosis lesions. The Journal of neuroscience : the official journal of the Society for Neuroscience 2011 Mar; 31(9).

Vidaurre OG, Liu J, Haines J, Sandoval J, Nowakowski R, Casaccia P. An integrated approach to design novel therapeutic interventions for demyelinating disorders. The European journal of neuroscience 2012 Jun; 35(12).

Haines JD, Inglese M, Casaccia P. Axonal damage in multiple sclerosis. The Mount Sinai journal of medicine, New York; 78(2).

Wu M, Hernandez M, Shen S, Sabo JK, Kelkar D, Wang J, O'Leary R, Phillips GR, Cate HS, Casaccia P. Differential modulation of the oligodendrocyte transcriptome by sonic hedgehog and bone morphogenetic protein 4 via opposing effects on histone acetylation. The Journal of neuroscience : the official journal of the Society for Neuroscience 2012 May; 32(19).

Inglese M, Oesingmann N, Casaccia P, Fleysher L. Progressive multiple sclerosis and gray matter pathology: an MRI perspective. The Mount Sinai journal of medicine, New York; 78(2).

Swiss VA, Nguyen T, Dugas J, Ibrahim A, Barres B, Androulakis IP, Casaccia P. Identification of a gene regulatory network necessary for the initiation of oligodendrocyte differentiation. PloS one 2011; 6(4).

Casaccia P. Anti-TANKyrase weapons promote myelination. Nature neuroscience 2011 Aug; 14(8).

DiNieri JA, Wang X, Szutorisz H, Spano SM, Kaur J, Casaccia P, Dow-Edwards D, Hurd YL. Maternal cannabis use alters ventral striatal dopamine D2 gene regulation in the offspring. Biological psychiatry 2011 Oct; 70(8).

Gil-Perotin S, Haines JD, Kaur J, Marin-Husstege M, Spinetta MJ, Kim KH, Duran-Moreno M, Schallert T, Zindy F, Roussel MF, Garcia-Verdugo JM, Casaccia P. Roles of p53 and p27(Kip1) in the regulation of neurogenesis in the murine adult subventricular zone. The European journal of neuroscience 2011 Oct; 34(7).

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.

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.

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.

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

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.

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, 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.

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.

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.

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;.

Huynh JL, Casaccia P. Defining the chromatin landscape in demyelinating disorders [review]. Neurobiol Dis 2009 Jul; 39(1): 47-52.

Kim JY, Casaccia-Bonnefil P. Interplay of hormones and p53 in modulating gender dimorphism of subventricular zone cell number. J Neurosci Res 2009 Nov; 87(15): 3297-3305.

Copray S, Huynh JL, Sher F, Casaccia-Bonnefil P, Boddeke E. Epigenetic mechanisms facilitating oligodendrocyte development, maturation, and aging. Glia 2009 Nov; 57(15): 1579-1587.

He Y, Kim JY, Dupree J, Tewari A, Melendez-Vasquez C, Svaren J, Casaccia P. Yy1: a molecular link between neuregulin and transcriptional modulation of peripheral myelination. Nature Neurosci 2010;.

Liu J, Sandoval J, Lopez-Rodas G, Doh S, Cai L, Casaccia P. Epigenetic Modifiers Are Necessary but Not Sufficient for Reprogramming Non-Myelinating cells into Myelin Gene-expressing Cells. PlosONE 2010;.

Kim JY, Casaccia P. HDAC1 in axonal degeneration : a matter of subcellular localization. Cell Cycle 2010;.

Swiss VA, Casaccia P. Cell-context specific role of the E2F/Rb pathway in development and disease [review]. Glia 2010 Mar; 58(4): 3.

Kim JY, Shen S, Dietz K, He Y, Howell O, Reynolds R, Casaccia P. HDAC1 nuclear export induced by pathological conditions is essential for the onset of axonal damage. Nat Neurosci 2010 Feb; 13(2): 180-189.

Germano L, Swiss V, Casaccia P. Primary brain tumors, neural stem cell, and brain tumor cancer cells: where is the link? [review]. Neuropharmacology 2010 May; 58(6): 903-910.

Dietz KC, Casaccia P. HDAC inhibitors and neurodegeneration: at the edge between protection and damage [review]. Pharmacol Res 2010 Jul; 62(1): 11-17.

Yu Y, Casaccia P, Lu QR. Shaping the oligodendrocyte identity by epigenetic control [review]. Epigenetics 2010 Feb; 5(2): 124-128.

Liu J, Casaccia P. Epigenetic regulation of oligodendrocyte identity [review]. Trends Neurosci 2010 Apr; 33(4): 193-201.

Kerns D, Vong GS, Barley K, Dracheva S, Katsel P, Casaccia P, Haroutunian V, Byne W. Gene expression abnormalities and oligodendrocyte deficits in the internal capsule in schizophrenia. Schizophr Res 2010 Jul; 120((1-3)): 150-158.

Mattan NS, Ghiani CA, Lloyd M, Matalon R, Bok D, Casaccia P, de Vellis J. J.Aspartoacylase deficiency affects early postnatal development of oligodendrocytes and myelination . Neurobiol Dis 2010 Jul;.

Industry Relationships

Physicians and scientists on the faculty of the Icahn School of Medicine at Mount Sinai often interact with pharmaceutical, device and biotechnology companies to improve patient care, develop new therapies and achieve scientific breakthroughs. In order to promote an ethical and transparent environment for conducting research, providing clinical care and teaching, Mount Sinai requires that salaried faculty inform the School of their relationships with such companies.

Dr. Casaccia did not report having any of the following types of financial relationships with industry during 2012 and/or 2013: consulting, scientific advisory board, industry-sponsored lectures, service on Board of Directors, participation on industry-sponsored committees, equity ownership valued at greater than 5% of a publicly traded company or any value in a privately held company. Please note that this information may differ from information posted on corporate sites due to timing or classification differences.

Mount Sinai's faculty policies relating to faculty collaboration with industry are posted on our website at http://icahn.mssm.edu/about-us/services-and-resources/faculty-resources/handbooks-and-policies/faculty-handbook. Patients may wish to ask their physician about the activities they perform for companies.

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