Mani S. Mahadevan, M.D.
Mani S. Mahadevan, M.D. Faculty Profile
Mani S. Mahadevan, M.D.
Professor of Pathology
Medical Director of Molecular
Medical School: University of
Ottawa, Ottawa, Canada. 1986
Internship: Victoria Hospital, London, Ontario,
Residency: University of Ottawa, Ottawa, Canada.
Research Fellowship: Children's Hospital of Eastern
Ontario (CHEO), Ottawa, Canada. 1991-1995
Our research is in the field of human
genetics. Specifically, we are studying the molecular genetics
and biology of myotonic dystrophy (DM), the most common inherited
neuromuscular disorder in adults. We have previously cloned the
gene for DM and identified the DM mutation as a CTG trinucleotide
repeat expansion in the 3’ untranslated region of a gene encoding a
serine-threonine protein kinase (DMPK). The DM mutation was one
of the first members of growing family of triplet repeat mutations
causing human disease. However, the mechanism by which it causes
disease is unknown. We are studying the effects of the DM
mutation on gene expression and RNA metabolism. 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’UTR mRNA in inhibiting normal muscle
development. Our data shows that the mutant DMPK 3’UTR 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. Furthermore, the
study of the DM mutation has led to an active research program in RNA
processing, RNA transport and muscle development.
Mahadevan M.S., R.S. Yadava, Q. Yu, S.
Balijepalli, C.D. Frenzel-McCardell, T.D. Bourne and L.H. Phillips
(2006). Reversible model of RNA toxicity and cardiac conduction defects
in myotonic dystrophy. Nat. Genet. 2006 Sept;
Mahadevan MS, Benson PV. Factor V null
mutation affecting the Roche LightCycler factor V Leiden assay.
Clin Chem. 2005 Aug;51(8):1533-5. No abstract
Mastroyiannopoulos NP, Feldman ML, Uney JB, Mahadevan
MS, Phylactou LA. Woodchuck post-transcriptional element
induces nuclear export of myotonic dystrophy 3' untranslated region
transcripts. EMBO Rep. 2005
Silverman LM, Mahadevan MS. Genotype-phenotype
correlations: assessing the influence of sequence variants on the
clinical phenotype. Clin Chem. 2005
Jan;51(1):8. No abstract available.
Amack JD, Mahadevan MS. Myogenic defects in
myotonic dystrophy. Dev Biol. 2004 Jan
A more complete list of Dr. Mahadevan's publications can be obtained