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Department of Neurology

Houston, Texas

BCM neurologists see patients through the Baylor Clinic and some of the world's leading specialty clinics.
Department of Neurology
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Paolo Moretti, M.D.

Dr. Paolo Moretti

Assistant Professor
of Neurology and Molecular & Human Genetics

Adjunct Assistant Professor
of Biochemistry and Cell Biology, Rice University

 

Medical School

M.D. (1990) University of Padua School of Medicine, Padua, Italy

Residency

Neurology, University of Michigan, Ann Arbor, MI

Fellowship

University of Padua School of Medicine, Italy
Columbia University, New York, NY
Clinical Genetics, Baylor College of Medicine, Houston, TX

Research Interests

The overall goal of my research program is to elucidate genetic and biochemical pathways of neuronal function and gene-environment interactions in the brain and to apply this knowledge to neurological disorders caused by dysfunction in these pathways. As model systems, we study Parkinson’s disease, a common neurodegenerative disorder that causes progressive motor disability in adults, and Rett syndrome, an autism spectrum disorder that generally affects 1-2 year-old girls.

Parkinson’s disease is a multifactorial neurological disorder. Several genes have been implicated in its pathogenesis and environmental factors have been shown to either cause parkinsonism (post-encephalitic parkinsonism and MPTP) or to be associated with an increased risk of Parkinson’s disease (rural living, pesticide use, well-water consumption and certain occupations). Lipid and vesicle dynamics, the ubiquitin–proteasome system, MAPKKK signaling, oxidative stress, mitochondrial function and microtubule stability have all been implicated in the pathogenesis of Parkinson’s disease. However, the relationships between these pathways remain to be elucidated. Furthermore, the molecular interactions between genetic and environmental factors are largely unknown, a key issue considering that the majority of Parkinson’s disease cases occur sporadically. We have taken a system-wide genetic approach to identify the interrelationship between pathways of molecular dysfunction in Parkinson’s disease. Our aim is the elucidation of the molecular pathogenesis of Parkinson’s disease and the design of preventative or neuroprotective treatment strategies.

Rett syndrome is an X-linked dominant neurodevelopmental disorder caused by mutations in the gene encoding Methyl-CpG binding protein 2 (MeCP2). Affected children have cognitive impairment, autistic manifestations and motor dysfunction. We have identified abnormalities in all three of these domains in Mecp2 308 mutant mice, demonstrating that these animals represent a faithful model of the human disorder. We are now pursuing the elucidation of genetic and cellular pathways affected by MeCP2 dysfunction and the identification of epigenetic strategies for modification of disease severity in Rett syndrome. MeCP2 is a DNA methylation-dependent transcriptional repressor and methyl donors such as folate and betaine modulate metastable DNA methylation. We have shown that dietary methyl donors modify disease severity in Mecp2 mutant mice improving general health, neurological function and survival. Studies are ongoing to reveal the mechanisms of pathogenesis and epigenetic modification of disease severity using a combination of genetic and molecular approaches.

Publications

Contact Information

Paolo Moretti, M.D.
Department of Neurology
Baylor College of Medicine
One Baylor Plaza, MS NB302
Houston, Texas 77030

Tel: 713-798-7573
Fax: 713-798-2723
Email: