{"id":223,"date":"2015-11-13T15:02:59","date_gmt":"2015-11-13T20:02:59","guid":{"rendered":"https:\/\/med.virginia.edu\/pathology\/?page_id=223"},"modified":"2020-04-08T08:54:59","modified_gmt":"2020-04-08T12:54:59","slug":"mani-s-mahadevan-m-d","status":"publish","type":"page","link":"https:\/\/med.virginia.edu\/pathology\/contact\/mani-s-mahadevan-m-d\/","title":{"rendered":"Mani S. Mahadevan, M.D."},"content":{"rendered":"

\"Mani<\/a>
\nProfessor of Pathology<\/p>\n

EDUCATION:<\/h4>\n

Medical School:<\/strong> University of Ottawa, Ottawa, Canada. 1986
\nInternship:<\/strong> Victoria Hospital, London, Ontario, Canada. 1986-1987
\nResidency:<\/strong> University of Ottawa, Ottawa, Canada. 1987-1991
\nResearch Fellowship:<\/strong> Children’s Hospital of Eastern Ontario (CHEO), Ottawa, Canada. 1991-1995<\/p>\n

RESEARCH:<\/h4>\n

Our research is in the field of human genetics.\u00a0 Specifically, we are studying the molecular genetics and biology of myotonic dystrophy (DM), the most common inherited neuromuscular disorder in adults.\u00a0 We have previously cloned the gene for DM and identified the DM mutation as a CTG trinucleotide repeat expansion in the 3\u2019 untranslated region of a gene encoding a serine-threonine protein kinase (DMPK).\u00a0 The DM mutation was one of the first members of growing family of triplet repeat mutations causing human disease.\u00a0 However, the mechanism by which it causes disease is unknown.\u00a0 We are studying the effects of the DM mutation on gene expression and RNA metabolism.\u00a0 These studies involve the establishment of cell culture and transgenic mouse models of disease pathogenesis, the identification and characterization of RNA-binding proteins interacting with the DMPK transcript, and studying the role of the mutant DMPK 3\u2019UTR mRNA in inhibiting normal muscle development.\u00a0 Our data shows that the mutant DMPK 3\u2019UTR mRNA is trapped as distinct foci in the nucleus, and that its expression is sufficient to inhibit normal muscle differentiation. Our long-term goals are to understand the molecular mechanisms underlying DM and the establishment of model systems with which new approaches to therapeutic intervention could be developed and studied.\u00a0 Furthermore, the study of the DM mutation has led to an active research program in RNA processing, RNA transport and muscle development.<\/p>\n

REFERENCES:<\/h4>\n