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If clinical practice and contact with patients are the charm of medicine, why do research?!

By etavares On 31 May, 2013 Research and Advanced Education | 2013 Comments Off on If clinical practice and contact with patients are the charm of medicine, why do research?! No tags

Project GAPIC/Gulbenkian: Dissecting the signaling mechanisms of IL-7-mediated autophagy regulation in T-cell acute lymphoblastic leukemia 

I have always had this secret ambition to find out what it is like “to do research”.

In my view, which I believe is shared by most students for whom medicine is a passion, clinical practice, diagnosis discussion and the contact with patients constitute the real charms of exercising the profession. Studying medicine and looking after patients is a brilliant exercise of integrating knowledge, prior experiences and the latest advances in science.

Being a doctor means, amongst other things, possessing the maximum scientific information about advances in medicine and having the opportunity to apply it. So, why do research? Why this ambition?

I believe that research experience is very rewarding in our training and can be a fantastic experience for students. It makes us tackle problems in a different way, think about them from a different perspective, direct our thoughts in a different direction, and it awakens our critical minds, which is essential to the practice of our future profession. Doing research means raising questions, investigating them, thinking about ways of acting upon them and shaping them. Basically, it is the beauty of being able to understand the essence of human biology in a different manner.

Whereas to me clinical practice means the art of knowing how to apply science, doing research is the opportunity to do science. Accordingly, as a student, it made sense to experience this other side of medicine as a complement of my training and personal experience. It then became apparent to me that I would like to conduct my Master’s Final Project in laboratory research, and I ended up choosing immune-oncology, an area which has always fascinated me because it is so promising. So I ended up being welcomed at the Cancer Biology Unit in the IMM. I say “welcomed” because, due to prior experience, I believe that feeling welcomed at a laboratory is essential to adapt, enjoy the work and feel part of the routines of the lab and of the actual team, which in turn has an impact on how seriously we pick up and conduct the work. I was also very pleased to submit the project to the GAPIC (Office for the Support of Scientific and Technological Research)/Gulbenkian programme, which approved and supported it. I then joined a project at the UBCA with Daniel Ribeiro, a researcher and PhD student, which aims to dissect and get to know the signalling mechanisms of IL-7 mediated autophagy regulation in T-cell acute lymphoblastic leukaemia.

Project Rationale
Acute lymphoblastic leukaemia (ALL) is the most common malignant neoplasm in children. The T cell phenotype (T-ALL), albeit less frequent, is the one that is associated with greater risk and poorer diagnosis, for which reason therapies targeting the signalling pathways in target cells involved in the tumour process are particularly promising. The IL-7 is an interleukin that induces the proliferation, differentiation and survival of normal T cells which is also present in the T-ALL microenvironment, having the potential to modulate the growth of leukaemia. Our lab has demonstrated in vivo that the IL-7 can accelerate the development of T-ALL in humans. It has also demonstrated that PI3K is a major effector in inducing T-ALL viability and proliferation by IL-7 through the activation of the PI3K/Akt/mTOR signalling pathway, with the mTOR serine threonine kinase being a key negative regulator of autophagy.

Autophagy is an intracellular process that promotes the degradation of cytoplasmic compartments that occurs at basal levels in normal cells. It is activated by nutrient deprivation as a compensatory mechanism. On the other hand, rapid proliferation cells, such as tumour cells, can activate autophagy as a survival mechanism, that is, as a pro-oncogenic mechanism. However, when persistent, it stops protecting tumour cells and leads to cell death, acquiring the role of tumour suppressor. A previous work of our laboratory conducted under the GAPIC-09-2012 project generated preliminary data that suggest that the IL-7 can inhibit autophagy in TAIL7 cells, which is a T-ALL cell strand very similar to the primary cells of patients. We also demonstrated that the IL-7 negatively regulates the lipidation and cleavage of LC3, a characteristic of the induction of autophagy, with a functional impact on the viability and activation of malignant T-cells.

Thus, the current project aims to further study the molecular mechanisms through which the IL-7 modulates autophagy in T-ALL cells and their functional consequences, so that new potential targets for future therapeutic intervention can be identified.

Working at the UBCA with an amazing group of people always willing to help me (specifically on this project) has been a very big asset. I have acquired and developed several skills that will certainly be very useful in my future life. It is interesting to realize that sometimes the results we obtain are not what we anticipated, but that does not render them less interesting. Thinking about and discussing these results becomes the biggest challenge and a great incentive for future work or strands within the same task. Although I am aware that my role in the lab is pretty small in the scope of the work that is conducted there, it has played a major role in my academic experience, for which reason I could not possibly be happier about my decision. I take the opportunity to thank my supervisor Professor João Barata for accepting me at the UBCA, the entire team, especially Daniel Ribeiro, for the time they have always had for me, and finally the GAPIC/Gulbenkian programme for accepting, supporting and funding the project.

Maria Inês Felizardo Lopes,
year 5 student of the Integrated Master Degree in Medicine, FMUL;
Final Master Degree Project conducted at the Cancer Biology Unit, Institute of Molecular Medicine.
Project Supervisor: Professor João Taborda Barata, UBCA, IMM.

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Index - News # 34 | mai. 2013
 Long Live the University of Lisbon | Prof. Fernandes e Fernandes
 Professor José Fernandes e Fernandes appointed as Honorary Member and Distinguished Fellow
 New UTL and UL MSc in Microbiology
 Constitution of the General Council and Senate Members – Election Results
 Eleições para os Órgãos Sociais da AEFML 2013/2014 | Resultados Eleitorais
 Professor Fausto Pinto appointed Honorary Member of the Hungarian Society of Cardiology
 Isabel do Carmo launches new book
 Ángel Bayo Prize awarded to Portuguese article
 Knowing in order to Intervene – Research and Teaching: what tensions? what challenges?
 Professor Francisco Pulido Valente 2013 Teaching Award – 20 years anniversary
 Cultura.ul.pt
 PhDs, Masters and Specialization Courses | FMUL 2013/2014
 Oncology and Cancer – Angiogenesis Unit| Prof. Susana Constantino
 Scientific Research Projects in Oncology, Prof. Sérgio Dias
 Oncology and Cancer – Cancer Biology Unit | Prof. João Taborda Barata
 If clinical practice and contact with patients are the charm of medicine, why do research?!
 Development and characterization of a cellular model of acquired resistance to cetuximab in colorectal cancer KRAS – and BRAF-wt human cell lines
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 FATAL | 2013 Edition
 Movie and Medicine, featured by Dr. António Pais de Lacerda
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 Indicadores do 16.º Programa “Educação pela Ciência” | Bolsas Gulbenkian/FMUL – 2012/2013
 IMM Rheumatology Series | 4 de Junho
 VI Forum de Projectos de Prevenção da Obesidade | 21 e 22 de Junho
 Crise e Saúde – Riscos e Oportunidades | 21 de Junho
 Curso de Introdução às Revisões Sistemáticas e Meta-análises | 28 e 29 de Junho
 IX Edição dos Prémios Hospital do Futuro | Candidaturas até 13 de Setembro
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100 AnosPropriedade e Edição: Faculdade de Medicina da Universidade de Lisboa NIPC: 502662875  Periodicidade: Mensal  Diretor: Prof. Doutor Fausto J. Pinto Conselho Editorial: Prof. Doutor Fausto J. Pinto, Profª. Doutora Ana Sebastião, Prof. Doutor Mamede de Carvalho, Prof. Doutor António Vaz Carneiro, Prof. Doutor Miguel Castanho, Dr. Luís Pereira  Equipa Editorial:  Ana Raquel Moreira, Cristina Bastos, Isabel Varela, Joana Sousa, Maria de Lurdes Barata, Rui Gomes, Sónia Teixeira  Colaboração:  Gabinete de Relações Públicas, Internacionais e Comunicação  Versão Inglesa: AP|PORTUGAL- Language Services  Conceção: Metatexto, Lda. e-mail: news@medicina.ulisboa.pt  Sede do Editor e Sede da Redação: Avenida Prof. Egas Moniz, 1649-028 Lisboa Estatuto Editorial Anotado na ERC 

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