Bioinformatics & Population Genetics for Multiple Sclerosis

In collaboration with:
Italian Superior Health Institute, Rome, RM, 00161, Italy.
Neurology and Department of Neurosciences, Mental Health and Sensory Organs, “Sapienza” University of Rome, S. Andrea Hospital-site, RM, 00189, Italy.
Institute of Biomembrane and Bioenergetics, Bari, BA, 70126, Italy.
Center for Experimental Neurological Therapies, Rome, Italy.

Multiple sclerosis is primarily an inflammatory disorder of the brain and spinal cord in which focal lymphocytic infiltration leads to damage of myelin and axons. Initially, inflammation is transient and remyelination occurs but is not durable. Hence, the early course of disease is characterised by episodes of neurological dysfunction that usually recover. However, over time the pathological changes become dominated by widespread microglial activation associated with extensive and chronic neurodegeneration, the clinical correlate of which is progressive accumulation of disability. Paraclinical investigations show abnormalities that indicate the distribution of inflammatory lesions and axonal loss (MRI); interference of conduction in previously myelinated pathways (evoked electrophysiological potentials); and intrathecal synthesis of oligoclonal antibody (examination by lumbar puncture of the cerebrospinal fluid); cf. pathology states : Multiple sclerosis is triggered by environmental factors in individuals with complex genetic-risk profiles. Licensed disease modifying agents reduce the frequency of new episodes but do not reverse fixed deficits and have questionable e-ects on the long-term accumulation of disability and disease progression. Future studies in multiple sclerosis will provide a new taxonomy on the basis of mechanisms rather than clinical empiricism, and so inform strategies for improved treatment at all stages of the disease.
Where Multiple Sclerosis is concerned, my research is focused on: Bioinformatics analysis, post-sequencing statistics, population genetics, and Genome Wide Association Studies (GWAS).

Papers:

1. [2011, article]
   R. Calabrese, M. Zampieri, R. Mechelli, V. Annibali, T. Guastafierro, F. Ciccarone, G. Coarelli, R. Umeton, M. Salvetti, and P. Caiafa, "Methylation-dependent PAD2 upregulation in multiple sclerosis peripheral blood," Multiple Sclerosis Journal, p. I, 2011.
   @ARTICLE{ salvetti-umeton2011ms,
  AUTHOR = {Roberta Calabrese and Michele Zampieri and Rosella Mechelli and Viviana Annibali and Tiziana Guastafierro and Fabio Ciccarone and Giulia Coarelli and Renato Umeton and Marco Salvetti and Paola Caiafa},
  TITLE = {Methylation-dependent {PAD2} upregulation in multiple sclerosis peripheral blood},
  JOURNAL = {Multiple Sclerosis Journal},
  PUBLISHER = {SAGE},
  YEAR = {2011},
  PAGES = {In Press},
  URL = {http://dx.doi.org/10.1177/1352458511421055},
  ABSTRACT = {Background: Peptidylarginine deiminase 2 (PAD2) and peptidylarginine deiminase 4 (PAD4) are two members of PAD family which are over-expressed in the multiple sclerosis (MS) brain. Through its enzymatic activity PAD2 converts myelin basic protein (MBP) arginines into citrullines - an event that may favour autoimmunity - while peptidylarginine deiminase 4 (PAD4) is involved in chromatin remodelling. Objectives: Our aim was to verify whether an altered epigenetic control of PAD2, as already shown in the MS brain, can be observed in peripheral blood mononuclear cells (PBMCs) of patients with MS since some of these cells also synthesize MBP. Methods: The expression of most suitable reference genes and of PAD2 and PAD4 was assessed by qPCR. Analysis of DNA methylation was performed by bisulfite method. Results: The comparison of PAD2 expression level in PBMCs from patients with MS vs. healthy donors showed that, as well as in the white matter of MS patients, the enzyme is significantly upregulated in affected subjects. Methylation pattern analysis of a CpG island located in the PAD2 promoter showed that over-expression is associated with promoter demethylation. Conclusion: Defective regulation of PAD2 in the periphery, without the immunological shelter of the blood-brain barrier, may contribute to the development of the autoimmune responses in MS.}
}
2. [2011, misc]
   C. Eleuteri, C. Veroni, R. Umeton, M. Salvetti, and C. Agresti, An extensive in vitro and ex vivo screening of registered drugs to identify new enhancer of endogenous remyelination, 2011.
   @MISC{ umeton2011posterms2,
  AUTHOR = {Eleuteri, C. and Veroni, C. and Umeton, R. and Salvetti, M. and Agresti, C.},
  TITLE = {An extensive in vitro and ex vivo screening of registered drugs to identify new enhancer of endogenous remyelination},
  HOWPUBLISHED = {Poster at 10th Europeglia Meeting on Glial Cells in Health and Diseases (GLIA) Prague, Czech Republic, 13-17 September 2011},
  Month = {September},
  YEAR = {2011},
  URL = {http://www.umeton.com/papers/Eleuteri-GLIA11.pdf}
}
3. [2011, misc]
   R. Umeton, V. Annibali, D. Vittori, R. Mechelli, S. Romano, C. Policano, G. Coarelli, C. Mattei, G. Ristori, and M. Salvetti, MicroRNA expression profile of B lymphocytes in Multiple Sclerosis, 2011.
   @MISC{ umeton2011posterms1,
  AUTHOR = {Umeton, R. and Annibali, V. and Vittori, D. and Mechelli, R. and Romano, S. and Policano, C. and Coarelli, G. and Mattei, C. and Ristori, G. and Salvetti, M.},
  TITLE = {MicroRNA expression profile of B lymphocytes in Multiple Sclerosis},
  HOWPUBLISHED = {Poster at 21st Conference of the Italian Neuroimmunology Society (AINI) Pollenzo, CN, Italy, 22-25 September 2011},
  Month = {September},
  YEAR = {2011},
  URL = {http://www.umeton.com/papers/Umeton-AINI11.pdf}
}
4. [2011, misc]
   R. Umeton, R. Pizzolato, G. Nicosia, and C. F. Dewey, OREMPdb, System Overview and First Queries in the Neurology Field, 2011.
   @MISC{ umeton2011posterb,
  AUTHOR = {Umeton, Renato and Pizzolato, Raffaella and Nicosia, Giuseppe and {Dewey},
  {C.F}},
  TITLE = {OREMPdb, System Overview and First Queries in the Neurology Field},
  HOWPUBLISHED = {Poster at 3rd Int. Workshop on Bio-Design Automation (IWBDA) San Diego, CA, USA, 5-9 June 2011},
  Month = {June},
  YEAR = {2011},
  URL = {http://wiki.bu.edu/ece-cidar/index.php/IWBDA_2011}
}