Skip to main content

Paulo Alexandre Ferreira

Associate Professor in Ophthalmology
Ophthalmology, Vitreoretinal Diseases & Surgery
Duec 3802, 2351 Erwin Road, Durham, NC 27710
2351 Erwin Road, Duec 3802, Aeri Bldg, Room 5002, Durham, NC 27710

Overview


The long-term goal of our research program is twofold. The first is to understand the interplay between intracellular signaling, intracellular trafficking and proteostasis in health and disease; the second is to uncover molecular players and mechanisms partaking in such processes that are amenable to therapeutic intervention in a variety of disease states. Presently, our research efforts are centered on dissecting the roles of two disease-associated protein interactomes assembled by the Ran-binding protein 2 (RanBP2) and the retinitis pigmentosa GTPase regulator-interacting protein 1 (RPGRIP1) in several neuronal cell types of the retina and brain that often undergo neurodegeneration upon a multiplicity of diseases with distinct etiologies.

The RanBP2 is a large and modular 358 kDa protein scaffold, which assembles a large multifunctional complex and acts a signal integrator of molecular and subcellular signaling and trafficking pathways critical to neuronal survival or function. Mutations or deficits in RanBP2 are linked to a variety of diseases processes ranging from neurodegeneration and necrosis to stress signaling and cancer. RanBP2 modulates the assembly or disassembly of several protein complexes with apparent disparate functions and implicated in molecular processes, such as nucleocytoplasmic and microtubule-based intracellular trafficking of proteins or organelles, protein homeostasis and biogenesis, modulation of protein-protein interactions (e.g. sumoylation), and control of cell division. Interdisciplinary approaches ranging from single molecule analysis to cell-based assays and genetically modified mouse models are employed to dissect selective cell type-dependent roles of proteins modulated dynamically by RanBP2 and underlying mechanisms in healthy and disease states.

The RPGRIP1 is also a modular protein, which associates directly with molecular partners, such as the retinitis pigmentosa GTPase regulator (RPGR) and nephrocystin-4 (NPHP4). Human mutations in the genes encoding RPGRIP1, RPGR and NPHP4 lead to severe ocular-renal, syndromic and non-syndromic retinal or renal diseases. These lead ultimately to blindness, loss of kidney function or both. Emerging data from our laboratory implicate the RPGRIP1 interactome in the regulation of the tethering, targeting, exiting and/or transport of selective retinal-renal and pre-ciliary components from the endoplasmic reticulum compartment to cilia. These processes serve as molecular determinants to the formation of subcellular structures/compartments that are critical to photoreceptor or tubular kidney cell functions . Current work is directed at dissecting: i) the biological and pathological roles of components of the RPGRIP1 interactome in retinal and kidney functions; ii) the molecular, cellular and pathophysiological bases of allelic-specific mutations and genetic heterogeneity affecting components of the RPGRIP1 interactome; iii) the identification of therapeutic targets and mechanisms dependent on the functions of the RPGRIP1 assembly complex and therapeutic approaches to delay the onset or progression of degeneration of photoreceptor, tubular kidney cells or both.

Current Appointments & Affiliations


Associate Professor in Ophthalmology · 2005 - Present Ophthalmology, Vitreoretinal Diseases & Surgery, Ophthalmology
Associate Professor in Pathology · 2010 - Present Pathology, Clinical Science Departments

Education, Training & Certifications


Purdue University · 1993 Ph.D.