Our group studies the molecular mechanisms involved in chronic retinal diseases with the aim of developing new genetic and pharmacological therapeutic strategies
The Retinal Pigment Epithelium (RPE) is a highly specialized layer of cells, representing a fundamental component of the visual unit. In many retinal disorders, photoreceptor degeneration occurs as a consequence of RPE dysfunction.
Our group combines expertise in retinal cell biology, both in normal and pathological conditions. For the latter, we have focused our studies on Choroideremia, an X-linked form of retinal degeneration. We are now extending our studies to dissect the role of the RPE in AMD. Furthermore, we are using differentiation methods to derive RPE from human ES and iPS cells. Our RPE in vitro system will be used for fundamental studies as well as for potential translational applications to treat retinal degeneration.
Diabetic retinopathy is a complication of diabetes and a leading cause of vision loss in the working age population worldwide. There are no effective treatments for preventing DR onset or progression to severe late stages. Our goal is to develop new genetic and pharmacological therapeutic strategies to overcome syn loss of function and gain of toxic function, taking advantage of the privileged status of the eye for both therapies.
Projects
- 2022-2025 - “NRF2 as a novel therapeutic target in early and intermediate age-related macular degeneration-NASCENT”
HR22-00569 ”la Caixa” Foundation; PL: Miguel Seabra; PI: Antonio Cuadrao, UAM, ES
KNOW MORE
- 2022-2023 - “The role of necroptosis in Choroideremia”
FCT EXPL/MED-OUT/0599/2021
PI: Pedro Antas
- 2021-2022 - "Modelling hyperglycemia through human retinal organoids: a 3D model of early Diabetic retinopathy for drug discovery"
iNOVA4Health.
PI: Sandra Tenreiro; Co-PIs: Gabriela Silva (CEDOC) and Cláudia Nunes dos Santos (CEDOC).
- 2021-2022 - "Exosomes in transcellular proteostasis and Age-Related Macular Degeneration"
iNOVA4Health.
Co-PI: Sandra Tenreiro;PI: João Ferreira (CEDOC).
- 2021-2022 - "Mechanisms of Cell Death in Chroideremia"
Fight for Sight UK
PI: Miguel Seabra
- 2018-2019 - "Correction of lysosomal dysfunction in Retinal Pigmented Epithelial (RPE) cells"
Boehringer Ingelheim
PI: Miguel Seabra
- 2018-2019 - "How CHM Defect Affects Cross Talk Between Organelles and Cellular Functions such as Mitochondria, Lysosome, Autophagy, and Proteostasis"
Choroideremia Research Foundation, USA
PI: Miguel C. Seabra
- 2019-2020 - "Mechanisms in Cell Death in Choroideremia"
Choroideremia Research Foundation, USA
PI: Miguel C. Seabra
- 2018-2021- “Lysosome dysfunction in age-related diseases”
Project 30385 (IC&DT – AAC n.º 02/SAICT/2017)
PI: Miguel C. Seabra
- 2018-2021- "Recovering neuronal function and promoting neuroprotection in diabetic retinopathy”
Project 29656 (IC&DT – AAC n.º 02/SAICT/2017)
PI: Sandra Tenreiro
- 2017-2020 - "Biomembrane: Bioengineered in vitro model of retinal pigmented epithelium of human eye"
M-ERA.NET 2/0005/2016 funded by FP7 EU programme
PI: Prof. Giovanni Vozzi, University of Pisa, Italy
- 01/01/2011 –31/12/2013 - “Molecular mechanisms of melanosome transfer and processing by keratinocytes"
Fundação para a Ciência e Tecnologia
PI: Miguel C. Seabra
- 01/10/2010 – 30/09/2013 - “Molecular dissection of the intracellular route of Plasmodium in macrophages and dendritic cells”
Fundação para a Ciência e Tecnologia
PI: Miguel C. Seabra
- 01/02/2010 – 31/01/2013 -“Subversion of the host endocytic pathway by Plasmodium sporozoites”
Fundação para a Ciência e Tecnologia
PI: Miguel C. Seabra
- 01/02/2010 – 31/01/2013- “Functional genomics studies of phagocytosis in retinal pigment epithelium”
Fundação para a Ciência e Tecnologia
PI: Miguel C. Seabra
- 01/01/2010 – 31/12/2012 - “Regulation of retinal growth factors secretion by Rab GTPases"
Fundação para a Ciência e Tecnologia
PI: Miguel C. Seabra
- 01/07/2010 – 30/06/2012 -“Expression of Rab GTPases in Breast Cancer”
Bolsa Terry Fox / Liga Portuguesa contra o Cancro
PI: Miguel C. Seabra
- 01/01/2008 – 31/12/2010 - “Molecular mechanisms of organelle motility”
Fundação para a Ciência e Tecnologia
PI: Miguel C. Seabra
- 01/10/2007 – 31/03/2010 - “Molecular mechanisms of parasitophorous vacuole formation in malaria infection”
Fundação para a Ciência e Tecnologia
PI: Miguel C. Seabra
Publications
- Dias SB, de Lemos L, Sousa L, Bitoque DB, Silva GA, Seabra MC, Tenreiro S. 2023. Age-Related Changes of the Synucleins Profile in the Mouse Retina. Biomolecules. 2023 Jan 15;13(1):180. doi: 10.3390/biom13010180.
- Cabral D, Ramtohul P, Kaden TR, Tenreiro S, Seabra MC, Freund KB.Eye (Lond). 2022. Hyperpigmented epiretinal membrane in macular telangiectasia type 2: imaging characteristics and correlation with transretinal pigment migration. 2022 Sep 22. doi: 10.1038/s41433-022-02260-7. Online ahead of print.
- Cabral D, Fradinho AC, Pereira T, Ramakrishnan MS, Bacci T, An D, Tenreiro S, Seabra MC, Balaratnasingam C, Freund KB.Transl Vis Sci Technol. 2022. Macular Vascular Imaging and Connectivity Analysis Using High-Resolution Optical Coherence Tomography. 2022 Jun 1;11(6):2. doi: 10.1167/tvst.11.6.2.
- Flores R, Carneiro Â, Neri G, Fradinho AC, Quenderra B, Barata MJ, Tenreiro S, Seabra MC. Diagnostics (Basel). 2022. Choroidal Vascular Impairment in Intermediate Age-Related Macular Degeneration. 2022 May 22;12(5):1290. doi: 10.3390/diagnostics12051290.
- Rita Flores, Angela Carneiro, Sandra Tenreiro, Miguel C Seabra. 2021. Retinal Progression Biomarkers of Early and Intermediate Age-Related Macular Degeneration. Life. Doi: 10.3390/life12010036. Online ahead of print. Review
- Escrevente E, Falcão AS, Hall MJ, Lopes-da-Silva M, Antas P, Mesquita MM, Ferreira IS, Cardoso MH, Fradinho AC, Futter CE, Tenreiro S, Seabra MC. Formation of lipofuscin-like autofluorescent granules in the retinal pigment epithelium requires lysosome dysfunction. IOVS 2021 (in press).
- Flores R, Carneiro Â, Vieira M, Tenreiro S, Seabra MC. Age-Related Macular Degeneration: Pathophysiology, Management, and Future Perspectives.Ophthalmologica. 2021 Jun 15. doi: 10.1159/000517520. Online ahead of print.
- Flores R, Carneiro A, Serra J, Gouveia N, Pereira T, Mendes JM, Coelho PS, Tenreiro S, Seabra MC. Correlation study between drusen morphology and fundus autofluorescence . Retina. 2021 Mar 1;41(3):555-562. doi: 10.1097/IAE.0000000000002881.
- Escrevente E, Falcão AS, Hall MJ, Lopes-da-Silva M, Antas P, Mesquita MM, Ferreira IS, Cardoso MH, Fradinho AC, Futter CE, Tenreiro S, Seabra MC. Formation of lipofuscin-like autofluorescent granules in the retinal pigment epithelium requires lysosome dysfunction. BioRxiv February 2021. doi: https://doi.org/10.1101/2021.02.23.432539.
- Meschede IP, Burgoyne T, Tolmachova T, Seabra MC, Futter CE. Chronically shortened rod outer segments accompany photoreceptor cell death in Choroideremia. PLoS One. 2020 Nov 17;15(11):e0242284. doi: 10.1371/journal.pone.0242284. eCollection 2020.
PMID: 33201897
- Gross T, Wack G, Syhr KMJ, Tolmachova T, Seabra MC, Geisslinger G, Niederberger E, Schmidtko A, Kallenborn-Gerhardt W. Rab27a Contributes to the Processing of Inflammatory Pain in Mice. Cells. 2020 Jun 18;9(6):1488. doi: 10.3390/cells9061488.
PMID: 3257093
- Fernández-Messina L, Rodríguez-Galán A, de Yébenes VG, Gutiérrez-Vázquez C, Tenreiro S, Seabra MC, Ramiro AR, Sánchez-Madrid F. Transfer of extracellular vesicle-microRNA controls germinal center reaction and antibody production. EMBO Rep. 2020 Apr 3;21(4):e48925. doi: 10.15252/embr.201948925. Epub 2020 Feb 19.PMID: 32073750
- Moreiras H, Pereira FJC, Neto MV, Bento-Lopes L, Festas TC, Seabra MC, Barral DC. The exocyst is required for melanin exocytosis from melanocytes and transfer to keratinocytes. Pigment Cell Melanoma Res. 2020 Mar;33(2):366-371. doi: 10.1111/pcmr.12840. Epub 2019 Nov 19.
PMID: 31665827.
- Meschede IP, Ovenden NC, Seabra MC, Futter CE, Votruba M, Cheetham ME, Burgoyne T. Symmetric arrangement of mitochondria:plasma membrane contacts between adjacent photoreceptor cells regulated by Opa1. Proc Natl Acad Sci U S A. 2020 Jul 7;117(27):15684-15693. doi: 10.1073/pnas.2000304117.
- Flores R, Carneiro A, Serra J, Gouveia N, Pereira T, Mendes JM, Coelho PS, Tenreiro S, Seabra MC.Correlation study between mprphology and fundus autofluorescence. Retina. 2020 Jun 26. doi: 10.1097/IAE.0000000000002881. Online ahead of print. PMID: 32604342
- Hayes MJ, Burgoyne T, Wavre-Shapton ST, Tolmachova T, Seabra MC, Futter CE. Remodeling of the Basal Labyrinth of Retinal Pigment Epithelial Cells With Osmotic Challenge, Age, and Disease. Invest Ophthalmol Vis Sci. 2019 Jun 3;60(7):2515-2524. doi: 10.1167/iovs.19-26784.
- Storck EM, Morales-Sanfrutos J, Serwa RA, Panyain N, Lanyon-Hogg T, Tolmachova T, Ventimiglia LN, Martin-Serrano J, Seabra MC, Wojciak-Stothard B, Tate EW. Dual chemical probes enable quantitative system-wide analysis of protein prenylation and prenylation dynamics. Nat Chem. 2019 Jun;11(6):552-561. doi: 10.1038/s41557-019-0237-6. Epub 2019 Apr 1.
- Sanzà P, Evans RD, Briggs DA, Cantero M, Montoliu L, Patel S, Sviderskaya EV, Itzen A, Figueiredo AC, Seabra MC, Hume AN. Nucleotide exchange factor Rab3GEP requires DENN and non-DENN elements for activation and targeting of Rab27a. J Cell Sci. 2019 Apr 30;132(9). pii: jcs212035. doi: 10.1242/jcs.212035.
- Moreiras H, Lopes-da-Silva M, Seabra MC, Barral DC. Melanin processing by keratinocytes: A non-microbial type of host-pathogen interaction? Traffic. 2019 Apr;20(4):301-304. doi: 10.1111/tra.12638.
Prizes and Awards
- 2015 - Grande Prémio BIAL de Medicina
Fundação Bial, Portugal
- 2006 - Entrepreneurship Prize, Neotec
Agência Nacional de Inovação SA, Portugal
- 1997 - Blind Research Award
Matilda Ziegler Foundation for the Blind Inc, USA
Open Positions
2 PhD Research Opportunities @ Molecular Mechanisms of Disease Lab
Contract for PhD Holder @ Molecular Mechanisms of Disease
Pursuant to the provisions of article 11, paragraph 2, of Decree-Law no. 57/2016, of August 29, it becomes public that by Dean’s decree of February 10, 2022, the opening of an international selection competition procedure was authorized for the completion of a PhD holder job vacancy for the exercise of scientific research activities financed by the Programa Operacional Regional de Lisboa in its FEDER component and by the Fundação para a Ciência e Tecnologia in its national component, under an uncertain fixed-term employment contract under the Labor Code in the Faculdade de Ciências Médicas|NOVA Medical School, Universidade NOVA de Lisboa.
Application deadline: March 25th 2022
PhD Opportunities @ Miguel Seabra Lab
Colaborations
- Clare Futter, Institute of Ophthalmology, UCL, London, UK
- Graça Raposo, Institut Curie, Paris, France
- Giovanni Vozzi, Università di Pisa – Centro di Ricerca “E. Piaggio”, Pisa, Italy
- Wojciech Swieszkowski, Warsaw University of Technology, Warsaw, Poland
- Eugene Smit, SNC Fibers, South Africa
- Miguel Veja, Allinky Biopharma, Spain
- Davida Gamm, Un. Wisconsin, Madison, USA
- Antonio Cuadrao, UAM, ES
- Lino Ferreira, CNC & CIBB, Universidade de Coimbra
- Susana Simões, Centro de Neurociências da Universidade de Coimbra
- Lino Ferreira, Centro de Neurociências da Universidade de Coimbra
- Nuno Matela, Instituto de Biofísica e Eng. Biomédica, Faculdade de Ciências da Universidade de Lisboa