Home > Faculty > Dr. Carlos T. Moraes

 

 

Carlos T. Moraes, Ph.D.

Professor of Neurology and Cell Biology & Anatomy
1095 NW 14th Terrace
Telephone: (305)243-5858
FAX: (305)243-3914
cmoraes@med.miami.edu
Molecular Bioenergetics Lab Page

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Curriculum Vitae

B.S., Escola Paulista de Medicina  1983
M.S.,Escola Paulista de Medicina  1987
Ph.D., Columbia University 1993
Assistant Professor, University of Miami 1993-1997
Associate Professor, University of Miami 1997-2005
Professor, University of Miami 2005-present

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Research Interests

The human mtDNA is a compact circular genome (16.6 kb) coding for components of the ATP-producing oxidative phosphorylation system. The contribution of the mitochondrial genome to cellular respiration, though vital, is not sufficient. Dozens of nuclear DNA (nDNA) coded proteins synthesized in the cytoplasm are imported into mitochondria and assembled with mitochondrially-synthesized proteins to form a functional oxidative phosphorylation system.

Mutations of either mtDNA or nDNA have been associated with devastating clinical syndromes. Organs with high energy requirements such as brain and muscle are preferentially affected. Symptoms include: seizures, strokes, muscle weakness, blindness, diabetes, and hearing loss. In addition to defining novel mtDNA abnormalities in patients with mitochondrial disorders, we are interested in understanding the molecular pathogenesis of these mutations and developing novel approaches to therapy. We use a full array of molecular and cell biology techniques for these studies.

Currently we have four major funded projects:

1) Development of genetic therapies for mitochondrial diseases. We are focusing on altering the ratio of mutant/wild-type mtDNA by the use of mitochondria-targeted endonucleases.

2) Development of animal models to study the pathogenesis of mitochondrial disorders. We are studying the molecular pathogenesis of several mitochondrial disorders with the help of genetically engineered mouse models.

3) The role of cytochrome c in apoptosis and development. WE have developed genetically modified mice with a defect in cytochrome c in various tissues. We are using this model to study the role of cytochrome c in apoptosis.

4) Compensating for a defect in oxidative phosphorylation by increasing mitochondrial biogenesis. We have found that the transcription coactivator PGC-1alpha, a major regulator of mitochondrial biogenesis, can compensate for partial mitochondrial defects when overexpressed.

 

A recombinant mitochondria-targeted restriction endonuclease was expressed in mouse skeletal muscle with the use of an adenovirus vector. The restriction endonuclease localized to muscle mitochondria (green). Because the restriction enzyme used (ApaLI) could digest a specific type of mtDNA sequence, subsequent analysis of the ratio "mutant"/wild-type mtDNA showed a marked reduction in the "mutant."

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Recent Publications

Cytochrome c Association with the Mitochondrial Inner Membrane is Impaired in the Central Nervous System of G93A-SOD1 Mice
Ilias G. Kirkinezos, Sandra R. Bacman, Dayami Hernandez, Jose Oca-Cossio, Laura J. Arias, Miguel A. Perez-Pinzon, Walter G. Bradley, and Carlos T. Moraes*
J. Neurosc. 25:164 –172 (2005)

Fast Adaptive Co-evolution of Nuclear and Mitochondrial Subunits of ATP Synthetase in Orangutan
Maria Pilar Bayona-Bafaluy, Stefan Müller, Carlos T. Moraes*
Mol. Biol. Evol. 22:716-724 (2005)

Double-Strand Breaks of Mouse Muscle mtDNA Promote Large-Deletions Similar to mtDNA Multiple Deletions in Humans
Sarika Srivastava and Carlos T. Moraes*
Hum. Mol. Genet. 14:893-902 (2005)

Mice lacking COX10 in skeletal muscle recapitulate the phenotype of progressive mitochondrial myopathies associated with cytochrome c oxidase deficiency
Francisca Diaz, Christine K. Thomas, Sofia Garcia, Dayami Hernandez and Carlos T. Moraes*
Hum. Mol. Genet. 14: 2737–2748 (2005)

Rapid Directional Shift of Mitochondrial DNA Heteroplasmy in Animal Tissues by a Mitochondrially-Targeted Restriction Endonuclease
Maria Pilar Bayona-Bafaluy, Bas Blits, Brendan Battersby, Eric A. Shoubridge, and Carlos T. Moraes*.
Proc. Natl. Acad. Sci. USA 102: 14392–14397 (2005)

Oxidative phosphorylation dysfunction modulates expression of extracellular matrix-remodeling genes and invasion
Corina van Waveren, Yubo Sun, Herman S. Cheung, and Carlos T. Moraes*
Carcinogenesis 27:409-418 (2006)

Cytochrome c Oxidase is Required for the Assembly/Stability of Respiratory Complex I in Mouse Fibroblasts
Francisca Diaz, Hirokazu Fukui, Sofia Garcia and Carlos T. Moraes*
Molecular and Cellular Biology 26:4872-4881 (2006)

Loss of Mcl-1 protein and inhibition of electron transport chain together induce anoxic cell death.
Brunelle JK, Shroff EH, Perlman H, Strasser A, Moraes CT, Flavell RA, Danial NN, Keith B, Thompson CB, Chandel NS.
Mol Cell Biol. 27:1222-35 (2007)

The Role of Cytochrome c in Apoptosis: Increased Sensitivity to TNF- α is Associated with Respiratory Defects But Not with Lack of Cytochrome c Release.
Uma D. Vempati, Francisca Diaz, Antoni Barrientos, Sonoko Narisawa, Abdul M. Mian, José Luis Millán, Lawrence H. Boise and Carlos T. Moraes*
Mol Cell Biol. 27:1771-1783 (2007)

Extended polyglutamine repeats trigger a feedback loop involving the mitochondrial complex III, the proteasome, and huntingtin aggregates.
Hirokazu Fukui1 and Carlos T. Moraes*
Human Molecular Genetics16:783-797 (2007)

PGC-1 α/ β Upregulation is Associated with Improved Oxidative Phosphorylation in Cells Harboring Nonsense mtDNA Mutations
Sarika Srivastava, John N. Barrett, and Carlos T. Moraes*
Human Molecular Genetics 16:993-1005 (2007)

Modulating mtDNA heteroplasmy by mitochondria-targeted restriction endonucleases in a “differential multiple cleavage-site” model.
Sandra R. Bacman, Sion L. Williams, Dayami Hernandez1 and Carlos T. Moraes*
Gene Therapy, in press Jun 28; [Epub ahead of print] (2007)

Cytochrome c Oxidase Deficiency in Neurons Decreases both Oxidative Stress and Amyloid Formation in a Mouse Model of Alzheimer’s Disease.
Hirokazu Fukui, Francisca Diaz, Sofia Garcia, Carlos T. Moraes*
Proc Natl. Acad. Sci. USAin press (2007)

View published research articles by Dr. Moraes in the National Library of Medicine

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