Jules and Doris Stein Research to Prevent Blindness Professor of Ophthalmology

Associate Professor of Molecular Genetics and Microbiology

Education

Purdue University, PhD, Neuroscience

UT Southwestern Medical Center, Postdoctoral Training

Phone

919-684-8457

Fax

919-684-3826

Email

ferre044@mc.duke.edu

Research Interests.

Paulo Ferreira, PhD, research interests include the molecular, cellular and genetic basis of retinal function, and pathogenesis of inherited retinopathies and allied diseases. Biological and pathological processes underlying trafficking and signaling pathways and neuronal cell death. 

Ferreira's research program has two key components. The first seeks to elucidate the molecular pathogenesis of X-linked retinitis pigmentosa type 3 (XlRP3) and allied diseases, such as Leber congenital amaurosis (LCA), that are often associated with systemic disorders. In particular, it aims at dissecting the biochemical and genetic network of biological and pathological processes underlying the function of the gene products encoded by the XlRP3 and LCA loci, and defining rational strategies to avert and/or delay the onset of the progressive death of selective retinal neurons. Emerging evidence supports that these diseases share pathological processes with other neurodegenerative disorders and thus, they may serve as paradigms in the understanding of neurodystrophies and the development of novel therapeutic approaches. The second research component seeks to determine the role of a large scaffold and pleiotropic protein, Ran-binding protein 2 (RanBP2), and its various interacting partners in biological and cellular processes underlying selective trafficking, signaling and metabolic pathways, and the molecular, genetic and (patho) physiological implications of these in non- and syndromic diseases of the retina. A wide array of biochemical, molecular, cellular and genetic approaches is employed to achieve these aims.

Representative Publications

1. Yi H, Friedman J, Ferreira PA. The cyclophilin-like domain of Ran-binding protein-2 modulates selectively the activity of the ubiquitin-proteasome system and protein biogenesis. J. Biol. Chem. 2007, in press

2. Cho KI, Cai Y, Yi H, Yeh A, Aslanukov A, Ferreira PA. Association of the Kinesin-Binding Domain of RanBP2 to KIF5B and KIF5C Determines Mitochondria Localization and Function. Traffic. 2007 Sep 20; in press

3. Moore DF, Gelderman MP, Ferreira PA, Fuhrmann SR, Yi H, Elkahloun A, Lix LM, Brady RO, Schiffmann R, Goldin E. Genomic abnormalities of the murine model of Fabry disease after disease-related perturbation, a systems biology approach. Proc Natl Acad Sci U S A. 2007 May 8;104(19):8065-70.

4. Aslanukov A, Bhowmick R, Guruju M, Oswald J, Raz D, Bush RA, Sieving PA, Lu X, Bock CB, Ferreira PA. RanBP2 modulates Cox11 and hexokinase I activities and haploinsufficiency of RanBP2 causes deficits in glucose metabolism. PLoS Genet. 2006 Oct;2(10):e177.

5. Lu X, Ferreira PA. Identification of novel murine- and human-specific RPGRIP1 splice variants with distinct expression profiles and subcellular localization. Invest Ophthalmol Vis Sci. 2005 Jun;46(6):1882-90.

6. Roepman R, Letteboer SJ, Arts HH, van Beersum SE, Lu X, Krieger E, Ferreira PA, Cremers FP. Interaction of nephrocystin-4 and RPGRIP1 is disrupted by nephronophthisis or Leber congenital amaurosis-associated mutations. Proc Natl Acad Sci U S A. 2005 Dec 20;102(51):18520-5.

7. Ferreira PA. Insights into X-linked retinitis pigmentosa type 3, allied diseases and underlying pathomechanisms. Hum Mol Genet. 2005 Oct 15;14 Spec No. 2:R259-67.

8. Lu X, Guruju M, Oswald J, Ferreira PA. Limited proteolysis differentially modulates the stability and subcellular localization of domains of RPGRIP1 that are distinctly affected by mutations in Leber's congenital amaurosis. Hum Mol Genet. 2005 May 15;14(10):1327-40.

9. Castagnet P, Mavlyutov T, Cai Y, Zhong F, Ferreira P. RPGRIP1s with distinct neuronal localization and biochemical properties associate selectively with RanBP2 in amacrine neurons. Hum Mol Genet. 2003 Aug 1;12(15):1847-63.

10 . Mavlyutov TA, Zhao H, Ferreira PA. Species-specific subcellular localization of RPGR and RPGRIP isoforms: implications for the phenotypic variability of congenital retinopathies among species. Hum Mol Genet. 2002 Aug 1;11(16):1899-907.