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

 

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."

 

Pathophysiology and Fate of Hepatocytes in a Mouse Model of Mitochondrial Hepatopathies.   Francisca Diaz, Sofia Garcia, Dayami Hernandez, Arie Regev, Adriana Rebelo, Jose Oca-Cossio and Carlos T. Moraes.   GUT 57:232-242 (2008) 

 

Transcriptional Co-expression and Co-regulation of Genes Coding for Components of the Oxidative Phosphorylation System.   Corina van Waveren and Carlos T. Moraes.   BMC Genomics, 9:18 (2008). 

 

A 3' UTR Modification of the Mitochondrial Rieske Iron Sulfur Protein in Mice Causes a Skin Pigmentation Phenotype.   Sofia Garcia, Francisca Diaz and Carlos T. Moraes.  J. Invest. Dermat. 128:2343-5 (2008). 

 

Activation of the PPAR/PGC-1a pathway prevents a bioenergetic deficit and effectively improves a mitochondrial mypathy phenotype.   Tina Wenz, Francisca Diaz, Bruce M. Spiegelman and Carlos T. Moraes.   Cell Metabolism  8:249-56 (2008). 

 

Mechanisms of formation and accumulation of mitochondrial DNA deletions in aging neurons.   Hirokazu Fukui and Carlos T. Moraes.   Human Molecular Genetics 18:1028-36 (2009).

 

Lack of cytochrome c in mouse fibroblasts disrupts assembly/stability of respiratory complexes I and IV.   Uma D. Vempati, Xianlin Han, Carlos T. Moraes.   Journal of Biological chemistry  284:4383-91 (2009). 

 

PGC-1 α/ β induced expression partially compensates for respiratory chain defects in cells from patients with mitochondrial disorders.   Sarika Srivastava, Francisca Diaz, Luisa Iommarini, Karine Aure, Anne Lombes and Carlos T. Moraes.   Human Molecular Genetics 18:1805-12 (2009). 

 

Endurance Exercise is Protective for Mice and Mitochondrial Myopathy.   Tina Wenz, Francisca Diaz, Dayami Hernandez and Carlos T. Moraes.   Journal of Applied Physiology 106:1712-1719 (2009).

 

Intra- and inter-molecular recombination of mitochondrial DNA after in vivo induction of multiple double-strand breaks.   Sandra R. Bacman, Sion L. Williams and Carlos T. Moraes.   Nucl. Acid Res. 37:4218-4226 (2009).

 

MTERF2 regulates oxidative phosphorylation by modulating mtDNA transcription.   Tina Wenz, Corneliu Luca, Alessandra Torraco and Carlos T. Moraes.   Cell Metabolism 9:499-511 (2009).

 

In vivo methylation of mtDNA reveals the dynamics of protein-mtDNA interactions.   Adriana Rebelo, Sion L. Williams and Carlos T. Moraes.   Nucl. Acid Res. in press (2009).