Dr. Paulo A. Ferreira

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Duke University
Duke University Medical Center
Ophthalmology, and Molecular Genetics and Microbiology
Jules and Doris Stein Research to Prevent Blindness ProfessorAppointed: 2005
Professional Headshot of Paulo A. Ferreira

Mailing Address

Duke University Medical Center
Departments of Ophthalmology, and Molecular Genetics and Microbiology
DUEC 3802
Erwin Road
Durham, North Carolina 27710
United States

Contact Information

Phone: (919) 684-8457
paulo.ferreira@duke.edu
http://dukeeyecenter.duke.edu/modules/eyectr_rsrch_basic/index.php?id=17

Qualifications

Ph.D., Purdue University, Neuroscience, 1993.
B.Sc., Jacksonville State University, Biology, 1988.
Licenciatura, University of Porto, Biological Sciences, 1988.

Expertise and Research Interests

The focus of my research program is twofold. The first project aims at dissecting the cross-talk between molecular and subcellular signaling and trafficking pathways determining neuronal survival and function, and underlying several pathophysiological states in the human. Currently, we are probing the roles of the Ran-binding protein 2 (RanBP2), a large pleiotropic and vital protein, in cell function and disease processes promoting the degeneration of neurons upon multiple stress stimuli and aging conditions. RanBP2 mediates the dynamic assembly of a heterogeneous protein complex comprised of several partners implicated in nucleocytoplasmic and microtubule-based intracellular trafficking pathways, signaling processes, protein homeostasis, modulation of protein-protein interactions (e.g. sumoylation), and control of cell division. Emerging data support that RanBP2 acts as a "signal integrator" of pathways conveying signals between various subcellular compartments. Interdisciplinary approaches are employed to probe the physiological and pathological implications of selective cross-talk pathways mediated by RanBP2 and its partners, and unravel molecular, cellular, and disease processes, with genetically modified mice, cell-based and biochemical assays. Recent mouse models of RanBP2 generated in my laboratory support a critical physiological role of RanBP2 in modulating energy metabolism, mitochondria transport and function, regulation of protein homeostasis by the ubiquitin-proteasome system, and survival of neurons upon deleterious stressors, in the central nervous system. Hence, RanBP2 and its partners emerge as key players in determining the expression of metabolic, neurodegenerative and aging diseases. The second project aims at dissecting the molecular pathogenesis of X-linked retinitis pigmentosa type 3(XlRP3), a preponderant, congenital, progressive and severe neurodegenerative disorder, leading to blindness and linked to allelic-specific systemic disorders, and that serves also as a paradigm to other neurodegenerative diseases. We identified protein isoforms, RPGRIP1s, which interact in vivo and in vitro with the XlRP3 gene product, RPGR. RPGRIP1 assembles a signaling and multifunctional interactome, which directly underlies multiple diseases processes. Human mutations in RPGRIP1 were found also to lead to severe and selective degeneration of photosensory neurons. The RPGRIP1 interactome mediates nucleocytoplasmic trafficking and signaling pathways that are blocked and/or dysfunctional by human mutations in the cognate genes. Future work is directed at dissecting i) the biological role of these proteins in neuronal function and mouse models, ii) the molecular, cellular and pathophysiological bases of allelic-specific mutations and genetic heterogeneity of XlRP3, RPGRIP1 and allied disease loci, and iii) the development of therapeutic approaches to delay the onset or cure XlRP3 and allied maladies.

Other Expertise

2002 - Present, Ad Hoc Reviewer, Integrative Biology and Neuroscience, National Science Foundation
2002 - Present, Ad Hoc Reviewer, The Wellcome Trust (U.K.)
2003 - Present, Ad Hoc Reviewer, Molecular and Cellular Biosiences, National Science Foundation
2006 - Present, Ad Hoc Reviewer, U.S.-Israel Binational Science Foundation

Keywords

COS Keywords:

Biochemistry, Biological Sciences, Blindness, Cell Biology, Cell Physiology, Central Nervous System, Genetic Models, Genetics, Molecular Biology, Molecular Pathology, Neurobiology, Neurodegenerative Diseases, Neurology, Neuroscience, Pathobiology, Pharmacology, Proteins and Macromolecules, Retinitis Pigmentosa, Signal Transduction, Toxicology, Transgenic Animals, Vision.

Additional Terms:

Biochemistry, Blindness, Cell Biology, Central Nervous System, GTP-binding Proteins, GTPase Effectors, GTPase Modulators, Genetic Models, Genetics, Glucose Metabolism, Kinesins, Leber Congenital Amaurosis, Mitochondria, Molecular Biology, Molecular Pathology, Motor Proteins, Neurobiology, Neurodegenerative Diseases, Neuron, Nuclear Export, Nuclear Import, Nucleocytoplasmic Trafficking, Pathobiology, Pharmacology, Photoreceptor, Protein Biogenesis, Protein Kinesis, Protein Trafficking, RPGR, RPGRIP, Ran-Binding Proteins, RanBP2, RanGTPase, Retina, Retinitis Pigmentosa, Signal Transduction, Transgenic Animals, Vision.

Languages

(Reading, Writing, Speaking)

Portuguese: (Fluent, Fluent, Fluent)
Spanish: (Fluent, Basic, Functional)
German: (Functional, Basic, Basic)

Memberships

American Society for Biochemistry and Molecular Biology
American Society for Cell Biology
Association for Research in Vision and Ophthalmology
Biochemical Society
Society for Experimental Biology and Medicine
Society for Neuroscience

Honors and Awards

2007, Editorial Board, Experimental Biology and Medicine
2007, Editorial Board, The Open Ophthalmology Journal
2005-2009, Jules and Doris Stein Research to Prevent Blindness Professorship Award, Research to Prevent Blindness
1998-1999, Research Award in Visual Sciences, The Karl Kirchgessner Foundation
1993-1994, Postdoctoral Science Fellowship, N.A.T.O.
1993, A.H. Ismail Interdisciplinary Program Doctoral Research Award, Purdue University
1991-1993, SCIENCE Predoctoral Fellowship (E.C.), E.C./F.C.T. (Portugal)
1989-1991, Predoctoral Science Fellowship, N.A.T.O.

Previous Positions

2001-2005, Associate Professor, Medical College of Wisconsin, Pharmacology and Toxicology
1997-2001, Assistant Professor, Medical College of Wisconsin, Pharmacology and Toxicology
1994-1997, Research Fellow, University of Texas Southwestern Medical Center at Dallas, Neuroscience
1994-1997, Instructor, University of Texas Southwestern Medical Center at Dallas, Neuroscience

Funding Received

  • The Karl Kirchgessner Foundation: , Unrestricted, Jun 1998 to Dec 1999.
  • Research to Prevent Blindness: Jules and Doris Stein Research to Prevent Blindness, 2005 to 2009.
  • National Institutes of Health (NIH): Molecular Pathogenesis of Retinitis Pigmentosa Type 3, 2001 to 2006.
  • National Institutes of Health (NIH): Structure-Function Analysis of RanBP2 in the Neuroretina, 1999 to 2007.

Publications

  • Won J, Gifford E, Smith RS, Yi H, Ferreira PA, Li T, Naggert JK, Nishina PM (Aug 2009) RPGRIP1 is essential for normal rod photoreceptor outer segment elaboration and morphogenesis., Human molecular genetics Abstract
  • Walsh MM, Yi H, Friedman J, Cho KI, Tserentsoodol N, McKinnon S, Searle K, Yeh A, Ferreira PA (Aug 2009) Gene and protein expression pilot profiling and biomarkers in an experimental mouse model of hypertensive glaucoma., Experimental biology and medicine (Maywood, N.J.), 234 (8), 918-30 Abstract
  • Cho KI, Yi H, Desai R, Hand AR, Haas AL, Ferreira PA (May 2009) RANBP2 is an allosteric activator of the conventional kinesin-1 motor protein, KIF5B, in a minimal cell-free system., EMBO reports, 10 (5), 480-6 Abstract
  • Cho KI, Yi H, Yeh A, Tserentsoodol N, Cuadrado L, Searle K, Hao Y, Ferreira PA (Feb 2009) Haploinsufficiency of RanBP2 is neuroprotective against light-elicited and age-dependent degeneration of photoreceptor neurons., Cell death and differentiation, 16 (2), 287-97 Abstract
  • Cho KI, Cai Y, Yi H, Yeh A, Aslanukov A, Ferreira PA (Dec 2007) Association of the kinesin-binding domain of RanBP2 to KIF5B and KIF5C determines mitochondria localization and function., Traffic (Copenhagen, Denmark), 8 (12), 1722-35 Abstract
  • Yi H, Friedman JL, Ferreira PA (Nov 2007) The cyclophilin-like domain of Ran-binding protein-2 modulates selectively the activity of the ubiquitin-proteasome system and protein biogenesis., The Journal of biological chemistry, 282 (48), 34770-8 Abstract
  • Moore DF, Gelderman MP, Ferreira PA, Fuhrmann SR, Yi H, Elkahloun A, Lix LM, Brady RO, Schiffmann R, Goldin E (May 2007) Genomic abnormalities of the murine model of Fabry disease after disease-related perturbation, a systems biology approach., Proceedings of the National Academy of Sciences of the United States of America, 104 (19), 8065-70 Abstract
  • Aslanukov A, Bhowmick R, Guruju M, Oswald J, Raz D, Bush RA, Sieving PA, Lu X, Bock CB, Ferreira PA (Oct 2006) RanBP2 modulates Cox11 and hexokinase I activities and haploinsufficiency of RanBP2 causes deficits in glucose metabolism., PLoS genetics, 2 (10), e177 Abstract
  • Roepman R, Letteboer SJ, Arts HH, van Beersum SE, Lu X, Krieger E, Ferreira PA, Cremers FP (Dec 2005) Interaction of nephrocystin-4 and RPGRIP1 is disrupted by nephronophthisis or Leber congenital amaurosis-associated mutations., Proceedings of the National Academy of Sciences of the United States of America, 102 (51), 18520-5 Abstract
  • Ferreira PA (Oct 2005) Insights into X-linked retinitis pigmentosa type 3, allied diseases and underlying pathomechanisms., Human molecular genetics, 14 Spec No. 2, R259-67 Abstract
  • Lu X, Ferreira PA (Jun 2005) Identification of novel murine- and human-specific RPGRIP1 splice variants with distinct expression profiles and subcellular localization., Investigative Ophthalmology & Visual Science, 46 (6), 1882-90 Abstract
  • Lu X, Guruju M, Oswald J, Ferreira PA (May 2005) Limited proteolysis differentially modulates the stability and subcellular localization of domains of RPGRIP1 that are distinctly affected by mutations in Leber's congenital amaurosis., Human Molecular Genetics, 14 (10), 1327-40 Abstract
  • 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, Human Molecular Genetics, 12(15), 1847-63, August 2003 Abstract
  • Mavlyutov TA, Cai Y, Ferreira PA, Identification of RanBP2- and kinesin-mediated transport pathways with restricted neuronal and subcellular localization, Traffic (copenhagen, Denmark), 3(9), 630-40, September 2002 Abstract
  • 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, Human Molecular Genetics, 11(16), 1899-907, Aug 2002 Abstract
  • Cai Y, Singh BB, Aslanukov A, Zhao H, Ferreira PA, The docking of kinesins, KIF5B and KIF5C, to Ran-binding protein 2 (RanBP2) is mediated via a novel RanBP2 domain, Journal of Biological Chemistry, 276(45), 41594-602, November 2001 Abstract
  • Fauser S, Aslanukov A, Roepman R, Ferreira PA, Genomic organization, expression, and localization of murine Ran-binding protein 2 (RanBP2) gene, Mammalian Genome : Official Journal of the International Mammalian Genome Society, 12(6), 406-15, June 2001 Abstract
  • Roepman R, Bernoud-Hubac N, Schick DE, Maugeri A, Berger W, Ropers HH, Cremers FP, Ferreira PA, The retinitis pigmentosa GTPase regulator (RPGR) interacts with novel transport-like proteins in the outer segments of rod photoreceptors, Human Molecular Genetics, 9(14), 2095-105, September 2000 Abstract
  • Roepman R, Schick D, Ferreira PA, Isolation of retinal proteins that interact with retinitis pigmentosa GTPase regulator by interaction trap screen in yeast, Methods in Enzymology, 316, 688-704, 2000 Abstract
  • Ferreira PA, Characterization of RanBP2-associated molecular components in neuroretina, Methods in Enzymology, 315, 455-68, 2000 Abstract
  • Singh BB, Patel HH, Roepman R, Schick D, Ferreira PA, The zinc finger cluster domain of RanBP2 is a specific docking site for the nuclear export factor, exportin-1, Journal of Biological Chemistry, 274(52), 37370-8, 1999 Abstract
  • Ferreira PA, Yunfei C, Schick D, Roepman R, The cyclophilin-like domain mediates the association of Ran-binding protein 2 with subunits of the 19 S regulatory complex of the proteasome, Journal of Biological Chemistry, 273(38), 24676-82, 1998 Abstract
  • Ferreira PA, Nakayama TA, Travis GH, Interconversion of red opsin isoforms by the cyclophilin-related chaperone protein Ran-binding protein 2, Proceedings of the National Academy of Sciences (USA), 94(4), 1556-61, 1997 Abstract
  • Ferreira PA, Nakayama TA, Pak WL, Travis GH, Cyclophilin-related protein RanBP2 acts as chaperone for red/green opsin, Nature, 383(6601), 637-40, 1996 Abstract
  • Ferreira PA, Hom JT, Pak WL, Retina-specifically expressed novel subtypes of bovine cyclophilin, Journal of Biological Chemistry, 270(39), 23179-88, 1995 Abstract
  • Ferreira PA, Pak WL, Bovine phospholipase C highly homologous to the norpA protein of Drosophila is expressed specifically in cones, Journal of Biological Chemistry, 269(5), 3129-31, 1994 Abstract
  • Ferreira PA, Shortridge RD, Pak WL, Distinctive subtypes of bovine phospholipase C that have preferential expression in the retina and high homology to the norpA gene product of Drosophila, Proceedings of the National Academy of Sciences (USA), 90(13), 6042-6, 1993 Abstract

Profile Details

Last Updated: 8/25/2009

COS Expertise ID #1036234
Reference this profile directly: http://myprofile.cos.com/pferreira