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From a very young age, I have always wanted to help improve other people’s lives. This motivated me to take BSc and MSc degrees in biomedical sciences at the University of Algarve to understand diseases' molecular mechanisms and potentially identify paths to new treatments. During this time, I discovered a deep interest in molecular and cellular biology and genetics. My career as a biomedical researcher started in 2012 with a short internship at the Faculty of Pharmacy University of Lisbon focused on the molecular diagnosis of neurometabolic disease. Later, as an MSc student, I studied the role of vitamin K-dependent proteins in ectopic calcification at the Centre of Marine Sciences (CCMAR-Algarve). After my MSc, I was offered a two-year research fellowship to keep developing the same research, which was crucial to improving my technical skills in the lab along with my critical thinking. As I have always been passionate about learning, in 2017 I decided to enroll in a Ph.D. program at the Faculty of Sciences University of Lisbon, Portugal, in collaboration with the University College Cork, Ireland. In this four-year program (the first two years were spent in Cork and the other two in Lisbon), I decided to broaden my horizons from diagnostics to characterizing disease mechanisms and exploring potential therapeutic strategies. Thus, I started working on Cystic Fibrosis and gene editing under the supervision of Carlos M. Farinha, Ph.D. and Patrick T. Harrison, Ph.D. My Ph.D. project focused on the development of state-of-the-art gene editing tools, first to develop new cell models carrying different CF-causing mutations to understand the effects of the different mutations on the transcriptome and proteome of the cells. This was crucial to get a better understanding of CF mechanisms, which can help predict disease severity, and, ultimately, uncover new drug targets. The second application was to use gene editing tools to develop novel strategies to correct the root cause of CF. After completing my PhD, I have focused my research on the W1282X-CFTR mutation, a nonsense mutation that is non-responsive to any of the currently approved CFTR modulator therapies. In 2021, we obtained initial funding from Cystic Fibrosis Foundation to work on the development of a base editing tool to correct W1282X-CFTR and understand which cells of the lung epithelia and how many of them we need to target to restore CFTR function in the lungs. From 2021 to 2023 in collaboration with University College Cork (where I spent one more year) and the Biosystems and Integrative Sciences Institute (BioISI), I developed a new cell model by gene editing carrying the W1282X-CFTR mutation on the BCi-NS1.1 background and patented a new base editing tool, called Split-ABE, which can correct W1282X-CFTR with minimal bystander effects (one of the major downsides of base editing). To continue expanding my knowledge and work towards the development of new therapies, in June 2023, I joined the Cell Line Development and Molecular Virology (CLD&MV) at iBET where I have been developing cell lines for viral vector manufacturing.
Identification

Personal identification

Full name
Lúcia Alexandra Rosa dos Santos

Citation names

  • Santos, Lúcia

Author identifiers

Ciência ID
1A10-41FE-21DA
ORCID iD
0000-0002-3748-3697

Knowledge fields

  • Natural sciences - Biological Sciences - Molecular Biology
  • Natural sciences - Biological Sciences - Cell Biology
  • Medical and Health Sciences - Medical Biotechnology - Gene-based Diagnostics and Therapeutic Interventions

Languages

Language Speaking Reading Writing Listening Peer-review
Portuguese (Mother tongue)
English Proficiency (C2) Proficiency (C2) Proficiency (C2) Proficiency (C2) Proficiency (C2)
Education
Degree Classification
2022
Concluded
Biologia (Doutoramento)
Major in Biologia de Sistemas
Universidade de Lisboa Faculdade de Ciências, Portugal
"Novel cell models to study Cystic Fibrosis – from disease mechanisms to new therapeutic approaches " (THESIS/DISSERTATION)
Aprovado com Distinção
2014
Concluded
Mestrado em Ciências Biomédicas (Mestrado)
Universidade do Algarve, Portugal
""Interaction studies of Gla-rich protein with bone morphogenetic proteins"" (THESIS/DISSERTATION)
17
2012
Concluded
Licenciatura em Ciências Biomédicas (Licenciatura)
Universidade do Algarve, Portugal
""Identificação e caracterização de déficites do Complexo da Piruvato Desidrogenase"" (THESIS/DISSERTATION)
14
Affiliation

Science

Category
Host institution
Employer
2023/06/15 - Current Contracted Researcher (Research) Instituto de Biologia Experimental e Tecnológica, Portugal
2022 - 2023/06/12 Contracted Researcher (Research) Universidade de Lisboa Instituto de Biossistemas e Ciências Integrativas, Portugal
2021 - 2022 Contracted Researcher (Research) University College Cork BioSciences Institute, Ireland
2015/01/01 - 2016/12/31 Research Assistant (Research) Centro de Ciências do Mar, Portugal
2013 - 2014 Research Trainee (Research) Centro de Ciências do Mar, Portugal
2012 - 2012 Research Trainee (Research) Universidade de Lisboa Faculdade de Farmácia, Portugal

Others

Category
Host institution
Employer
2019 - 2021 PhD Student Universidade de Lisboa Instituto de Biossistemas e Ciências Integrativas, Portugal
2017 - 2019 PhD Student University College Cork BioSciences Institute, Ireland
Projects

Grant

Designation Funders
2017 - 2022 Novel cell models to study Cystic Fibrosis – from disease mechanisms to new therapeutic approaches
PD/BD/130969/2017
PhD Student Fellow
Universidade de Lisboa Faculdade de Ciências, Portugal
Concluded

Contract

Designation Funders
2015 - 2016 New insights into the mechanism of vascular calcification in chronic kidney disease (CKD): the role of GRP
PTDC/BIM-MEC/1168/2012
Research Fellow
Concluded
2012 - 2014 Insights into Gla-rich Protein (GRP) function and molecular mechanism of action in vascular calcification (BioGlaGRP)
Master Student Fellow
Universidade do Algarve Faculdade de Ciências e Tecnologia
Concluded
Outputs

Publications

Conference poster
  1. Santos, Lúcia; Joana Alves; Carlos M. Farinha; Harrison, Patrick T.. "A precise adenine base editor corrects W1282X-CFTR without bystander effects.". Paper presented in 18th ECFS Basic Science Conference, 2023.
  2. Pankonien, Ines; Cláudia Rodrigues; Filipa B. Simões; Santos, Lúcia; Carlos M. Farinha; Margarida D. Amaral. "Role of CFTR in airway epithelial regeneration and repair: studies from novel human basal cell lines". Paper presented in 18th ECFS Basic Science Conference, 2023.
  3. Andreia Henriques; Santos, Lúcia; Carlos M. Farinha. "Signatures associated with differentially expressed genes and proteins in G542X-CFTR: clues to novel therapeutic targets?". Paper presented in North American Cystic Fibrosis Conference, 2023.
  4. Santos, Lúcia; Joana Alves; Carlos M. Farinha; Patrick T. Harrison. "Development of an improved adenine base editor to correct W1292X-CFTR with reduced bystander effects". Paper presented in North American Cystic Fibrosis Conference, 2023.
  5. Pankonien, Ines; Cláudia Rodrigues; Filipa B. Simões; Santos, Lúcia; Carlos M. Farinha; Margarida D. Amaral. "Role of CFTR in airway epithelial regeneration and repair: Studies from novel human basal cell lines". Paper presented in North American Cystic Fibrosis Conference, 2023.
  6. S. Ramalho, Sofia; Santos, Lúcia; Margarida D. Amaral; André O. Falcão; Carlos M. Farinha. "Exploring the endoplasmic reticulum retention mechanisms to rescue the rare CFTR mutation N1303K". Paper presented in 17th ECFS Basic Science Conference, 2022.
  7. Karen Mention; Kader Cavusoglu-Doran; Santos, Lúcia; David J. Sanz; Anya T. Joynt; Carlos M. Farinha; Neeraj Sharma; Patrick T. Harrison. "Correction of the W1282X CFTR variant by gene editing with two techniques alternative to homology-directed repair". Paper presented in 17th ECFS Basic Science Conference, 2022.
  8. Santos, Lúcia; Nascimento, Rui; Duarte, Aires; Patrick T. Harrison; Gama-Carvalho, Margarida; Carlos M. Farinha. "Transcriptomic and proteomic analysis identify changes associated with several prototypical cystic fibrosis-causing mutations". Paper presented in 17th ECFS Basic Science Conference, 2022.
  9. Santos, Lúcia; Carlos M. Farinha; Patrick T. Harrison. "Temporal-spatial CRISPR base editing to identify target cells for genetic-based therapies". Paper presented in North American Cystic Fibrosis Conference, 2022.
  10. Santos, Lúcia; Sanz, D. J.; Cavusoglu-Doran, K.; Mention, K.; Farinha, C. M.; Harrison, P. T. "Gene and Base Edited Cell Models of Cystic Fibrosis-causing Mutations". Paper presented in 16th ECFS Basic Science Conference, 2019.
  11. Santos, Lúcia; Sanz, D. J.; Cavusoglu-Doran, K.; Mention, K.; Farinha, C. M.. "Gene and Base Edited Cell Models of Cystic Fibrosis-causing Mutations". Paper presented in 22nd Annual Meeting American Society of Gene and Cell Therapy, 2019.
  12. Karen Mention; Kader Cavusoglu-Doran; Santos, Lúcia; David J. Sanz; Martina Scallan; Patrick T. Harrison. "Comparison of three genome editing techniques to correct the common W1282X mutation responsible for cystic fibrosis". Paper presented in 16th ECFS Basic Science Conference, 2019.
  13. Karen Mention; Kader Cavusoglu-Doran; Santos, Lúcia; David J. Sanz; Martina Scallan; Patrick T. Harrison. "Comparison of three genome editing techniques to correct the common W1282X mutation responsible for cystic fibrosis". Paper presented in ASGCT 22nd Annual Meeting, 2019.
  14. Santos, Lúcia; Sanz, D. J.; Cavusoglu-Doran, K.; Mention, K.; Farinha, C. M.; Harrison, P. T.. "Development Of Gene Edited Cell Models To Study Cystic Fibrosis". Paper presented in 15th ECFS Basic Science Conference, 2018.
  15. Santos, Lúcia; Rafael, Marta S.; Viegas, Carla S. B.; Simes, Dina C.. "Studies towards unveiling potential interaction partners of Gla-rich protein (GRP), a potential regulator of pathological calcification related diseases". Paper presented in XVIII Congress of the Portuguese Biochemical Society, 2014.
  16. Martins, A.; Santos, Lúcia; Gonçalves, R.. "ß-cells regeneration in diabetes type 1". Paper presented in 8º Encontro Internacional da Sociedade Portuguesa para as Células Estaminais e Terapia Celular, 2013.
Journal article
  1. Mention, Karen; Cavusoglu-Doran, Kader; Joynt, Anya T; Santos, Lúcia; Sanz, David; Eastman, Alice C; Merlo, Christian; et al. "Use of adenine base editing and homology-independent targeted integration strategies to correct the cystic fibrosis causing variant, W1282X". Human Molecular Genetics 32 23 (2023): 3237-3248. http://dx.doi.org/10.1093/hmg/ddad143.
    10.1093/hmg/ddad143
  2. Santos, Lúcia; Nascimento, Rui; Duarte, Aires; Railean, Violeta; Amaral, Margarida D.; Harrison, Patrick T.; Gama-Carvalho, Margarida; Farinha, Carlos M.. "Mutation-class dependent signatures outweigh disease-associated processes in cystic fibrosis cells". Cell & Bioscience 13 1 (2023): http://dx.doi.org/10.1186/s13578-023-00975-y.
    10.1186/s13578-023-00975-y
  3. Santos, Lúcia. "CRISPR/Cas9, a decade of genome editing tools to fix the DNA". Science Reviews. Biology 1 1 (2022): 16-23. http://dx.doi.org/10.57098/scirevs.biology.1.1.3.
    10.57098/scirevs.biology.1.1.3
  4. Lúcia Santos; Karen Mention; Kader Cavusoglu-Doran; David J. Sanz; Mafalda Bacalhau; Miquéias Lopes-Pacheco; Patrick T Harrison; Carlos M Farinha. "Comparison of Cas9 and Cas12a CRISPR editing methods to correct the W1282X-CFTR mutation". Journal of Cystic Fibrosis (2022): https://doi.org/10.1016/j.jcf.2021.05.014.
    10.1016/j.jcf.2021.05.014
  5. Mention, Karen; Santos, Lúcia; Harrison, Patrick T.. "Gene and Base Editing as a Therapeutic Option for Cystic Fibrosis—Learning from Other Diseases". Genes 10 5 (2019): 387. http://dx.doi.org/10.3390/genes10050387.
    10.3390/genes10050387
  6. Viegas, Carla S.B.; Santos, Lúcia; Macedo, Anjos L.; Matos, António A.; Silva, Ana P.; Neves, Pedro L.; Staes, An; et al. "Chronic Kidney Disease Circulating Calciprotein Particles and Extracellular Vesicles Promote Vascular Calcification". Arteriosclerosis, Thrombosis, and Vascular Biology 38 3 (2018): 575-587. http://dx.doi.org/10.1161/atvbaha.117.310578.
    10.1161/atvbaha.117.310578
  7. Viegas, Carla S. B.; Costa, Rúben M.; Santos, Lúcia; Videira, Paula A.; Silva, Zélia; Araújo, Nuna; Macedo, Anjos L.; et al. "Gla-rich protein function as an anti-inflammatory agent in monocytes/macrophages: Implications for calcification-related chronic inflammatory diseases". PLOS ONE 12 5 (2017): e0177829. http://dx.doi.org/10.1371/journal.pone.0177829.
    10.1371/journal.pone.0177829
  8. Viegas, Carla; Santos, Lúcia; Macedo, Anjos; Morais, Rute; Silva, Ana; Neves, Pedro; Matos, António; Vermeer, Cees; Simes, Dina. "MO055CIRCULATING CALCIPROTEIN PARTICLES AND EXTRACELLULAR VESICLES AS NOVEL PLAYERS IN CHRONIC KIDNEY DISEASE VASCULAR CALCIFICATION. A ROLE FOR GLA-RICH PROTEIN". Nephrology Dialysis Transplantation 32 suppl_3 (2017): iii67-iii68. http://dx.doi.org/10.1093/ndt/gfx123.mo055.
    10.1093/ndt/gfx123.mo055
  9. Viegas, Carla S. B.; Macedo, Anjos L.; Morais, Rute; Santos, Lúcia; Matos, António P. A.; Silva, Ana P.; Neves, Pedro; Simes, Dina C.. "Dysregulated fetuin–mineral complexes are linked to vascular calcification in chronic kidney disease: The role of Gla-rich protein". Ultrastructural Pathology 41 1 (2017): 78-80. http://dx.doi.org/10.1080/01913123.2016.1269490.
    10.1080/01913123.2016.1269490
Thesis / Dissertation
  1. "Novel cell models to study Cystic Fibrosis – from disease mechanisms to new therapeutic approaches". PhD, Universidade de Lisboa, 2022.
  2. Santos, Lúcia. "Interaction studies of Gla-rich protein with bone morphogenetic proteins". Master, Universidade do Algarve - Campus de Gambelas, 2014.
  3. Santos, Lúcia. "Identificação e caracterização de déficites do Complexo da Piruvato Desidrogenase". Degree, Universidade do Algarve - Campus de Gambelas, 2012.

Intellectual property

Patent
  1. Harrison, Patrick T.; Santos, Lúcia. 2022. "CRISPR split Adenine Base Editor and uses thereof.".
    Pending
Activities

Oral presentation

Presentation title Event name
Host (Event location)
2023 A precise adenine base editor corrects W1282X-CFTR without bystander effects. 18th ECFS Basic Science Conference
European Cystic Fibrosis Society (Dubrovnik, Croatia)
2023 Mutation class dependent signatures outweigh disease associated processes in cystic fibrosis cells 46th European Cystic Fibrosis Conference
(Vienna, Austria)
2023 Development of an improved adenine base editor to correct W1282X-CFTR with reduced bystander effects North American Cystic Fibrosis Conference
(Phoenix, United States)
2022 Transcriptomic and proteomic analysis identify changes associated with several prototypical cystic fibrosis-causing mutations. 17th ECFS Basic Science Conference
European Cystic Fibrosis Society (Albufeira, Portugal)
Distinctions

Award

2023 The Gerd Döring Award
European Cystic Fibrosis Society, Denmark