Molecular Mechanisms of Disease

Miguel Seabra2

Miguel Seabra

Principal Investigator

CV

Location:

CEDOC
Campus Sant'Ana
Pólo de Investigação, NMS, UNL
Rua Câmara Pestana, nº 6
1150-082 Lisboa, Portugal

Phone: (+351) 218 803 033
Fax: (+351) 218 851 920
E-mail: miguel.seabra(at)nms.unl.pt

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The main aim of our group is to understand fundamental cellular processes such as membrane traffic and how they contribute to human disease. We use a variety of research approaches, including cell culture, microscopy, molecular biology and mouse models. We aim at developing new molecular tools, testing biomarkers and uncovering new gene and cell-based treatments, in an effort to tackle genetic and chronic diseases.
 

Research Areas

Retinal Degeneration
- Cell and Molecular Biology of the Retinal Pigment Epithelium (RPE)
- Age-Related Macular Degeneration (AMD)
- Gene- and Cell-based therapies focusing on the RPE

Skin Pigmentation
- Mechanisms of pigment release by melanocytes
- Mechanisms of pigment uptake and processing by keratinocytes
- Melanocyte/keratinocyte cross-talk

Cancer Biomarkers
- Rab GTPases as novel markers in breast and oral cancer

:: Retinal Degeneration
Retinal degeneration disorders affect millions of people worldwide and constitute a set of incurable diseases that gradually progress to blindness. Current treatments focus mainly on symptom management, even though there are still large gaps in our knowledge regarding eye homeostasis and respective control mechanisms. 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.

:: Skin Pigmentation
Regulation of skin pigmentation relies on an intricate crosstalk between the pigment-producing cells – melanocytes – and pigment-recipient cells – keratinocytes. The specific molecular mechanisms, which induce melanocytes to produce and transfer pigment to keratinocytes are mostly unknown. Our group aims at decoding the dialogue between these two skin cell types so as to understand the molecular basis for baseline pigmentation and pigmentation disorders.

:: Cancer Biomarkers
Our work is based on a collaborative study with several Hospitals in the Lisbon area. We focus on developing novel early diagnostic tools and evaluation of disease progression for oral and breast cancer. Oral cancer has high incidence and prevalence rates, even though the oral cavity can be easily observed. Early diagnostic methods are crucial, in order to decrease morbidity and mortality associated to this disease. On the other hand, breast cancer is one of the most prevalent cancers worldwide. SInce Rab GTPases have been implicated in multiple cancers, our group focuses mainly on Rab25 and Rab27 as potential biomarkers of disease progression in these types of cancer.

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- “Molecular mechanisms of parasitophorous vacuole formation in malaria infection”
01/10/2007 – 31/03/2010
Fundação para a Ciência e Tecnologia

- “Molecular mechanisms of organelle motility”
01/01/2008 – 31/12/2010
Fundação para a Ciência e Tecnologia

- “Functional genomics studies of phagocytosis in retinal pigment epithelium”
01/02/2010 – 31/01/2013
Fundação para a Ciência e Tecnologia

- “Molecular dissection of the intracellular route of Plasmodium in macrophages and dendritic cells”
01/10/2010 – 30/09/2013
Fundação para a Ciência e Tecnologia

- “Subversion of the host endocytic pathway by Plasmodium sporozoites”
01/02/2010 – 31/01/2013
Fundação para a Ciência e Tecnologia

- “Regulation of retinal growth factors secretion by Rab GTPases
01/01/2010 – 31/12/2012
Fundação para a Ciência e Tecnologia

- “Molecular mechanisms of melanosome transfer and processing by keratinocytes
01/01/2011 –31/12/2013
Fundação para a Ciência e Tecnologia

- “Expression of Rab GTPases in Breast Cancer”
01/07/2010 – 30/06/2012
Bolsa Terry Fox / Liga Portuguesa contra o Cancro

  • Hendrix A, Maynard D, Pauwels P, Braems G, Denys H, Van den Broecke R, Belle SV, Cocquyt V, Gespach C, Bracke M, Seabra MC, Gahl WA, Wever OD, Westbroek W. The secretory small GTPase RAB27B regulates invasive tumor growth and metastasis through extracellular HSP90. J. Nat. Canc. Inst., in press (IF: 14.933)
  • Ostrowski M, Carmo NB, Krumeich S, Fanget I, Raposo G, Savina A, Moita CF, Schauer K, Hume AN, Freitas RP, Goud B, Benaroch P, Hacohen N, Fukuda M, Desnos C, Seabra MC, Darchen F, Amigorena S, Moita LF, Thery C. Rab27a and Rab27b control different steps of the exosome secretion pathway. Nature Cell Biol., 2010 Jan;12(1):19-30; sup pp 1-13. (IF: 17.776)
  • Figueiredo AC, Wasmeier C, Tarafder AK, Ramalho JS, Baron RA, Seabra MC. Rab3GEP is the non-redundant guanine nucleotide exchange factor for Rab27a in melanocytes. J Biol Chem. 2008 Aug 22;283(34):23209-16. (IF: 5.581)
  • Lopes VS, Ramalho JS, Owen DM, Karl MO, Strauss O, Futter CE, Seabra MC. The ternary Rab27a-Myrip-Myosin VIIa complex regulates melanosome motility in the retinal pigment epithelium. Traffic. 2007 May;8(5):486-99. (IF: 5.709 )
  • Tolmachova T, Abrink M, Futter CE, Authi KS, Seabra MC. Rab27b regulates number and secretion of platelet dense granules. Proc Natl Acad Sci U S A. 2007 Apr 3;104(14):5872-7. (IF: 9.380)

- Instituto Gulbenkian de Ciência - IGC, PT

- Imperial College London, UK

- Instituto Biomédico de Investigação da Luz e Imagem – IBILI, PT

- Institute of Ophthalmology, UCL, UK

- Institut Curie, FR

- University of Southern California, USA

- The Scripps Research Institute, USA

- MRC Laboratory for Molecular Cell Biology, UK

- University of Aberdeen, UK

- Arab Emirates University, UAE

- Ghent University Hospital, USA

- National Institutes of Health - NIH, USA

Miguel Seabra Group2