FMUL News
Pfizer Awards distinguish two IMM Teams in the Areas of HIV and Cancer
Clinical Immunology Unit team coordinated by Professor Ana Espada de Sousa (Rita Cavaleiro, first author of the work, fifth from right).
The winners of both the 2008 Pfizer Prizes, attributed every year to research works in medicine, are researchers at the IMM. The awards, worth twenty thousand euros each, were awarded respectively to works carried out in the IMM’s Clinical Immunology Unit and Cancer Biology Unit.
Rita Cavaleiro is the first author of the work “Monocyte-mediated T cell suppression by HIV-2 envelope proteins” (authors: Rita Cavaleiro, Gregory J. Brunn, Adriana S. Albuquerque, Rui M. M. Victorino, Jeffrey L. Platt and Ana E. Sousa), awarded the Pfizer Clinical Research Prize and initially published in the magazine European Journal of Immunology. The study shows that the envelope proteins of the HIV-2 virus limit the lymphocyte activation of the infection, resulting in a more benign evolution of the disease when compared to HIV-1 infection, and opens up prospects in the development of new therapies based on the properties of the proteins present in the HIV-2 envelope.
The work that received the Pfizer 2008 Prize for Basic Research was published in the Journal of Clinical Investigation, and is titled: “PTEN Posttranslational Inactivation and Hyperactivation of the PI3K/Akt Pathway Sustain Primary T Cell Leukemia Viability” (authors: Ana Silva, J. Andrés Yunes, Bruno A. Cardoso, Leila R. Martins, Patrícia Y. Jotta, Miguel Abecasis, Alexandre E. Nowill, Nick R. Leslie, Angelo A. Cardoso, and Joao T. Barata).
The study was carried out at the IMM Cancer Biology Unit in partnership with foreign teams, and is the result of research into a T type of leukaemia, which particularly affects children and young adults.
The work focused specifically on the study of the PTEN protein, which acts inside human cells as an obstacle to the development of tumours. Until now it was thought that inactivation of PTEN, and the consequent developing of tumours, would essentially take place on the level of genes; that is, that genetic mutations led to the production of dysfunctional PTEN. What the researchers show in the award-winning work is that even in cells where PTEN production is normal the inactivation of the protein may occur due to the action of another protein, called CK2.
“We analysed the expression of PTEN in the cells of patients with acute T-cell lymphoblastic leukaemia. When this protein is no longer present in the cell there is a tendency for the tumour to be developed”, explains João Taborda Barata, director of the IMM Cancer Biology Unit and head of the present research action. However, after verifying that “in this type of tumour, the suppressor (PTEN) is present in the cells with normal levels” the team tried to discover this paradox.
The researchers studied leukemic cells taken from patients with T leukaemia, and saw that in these cells the CK2 chemically modifies the normal PTEN normal, adding a phosphate group to it. They also saw that this chemical modification leads to the inactivation of the PTEN. The study also recorded that in these leukemic cells there is an increase in oxygen radicals, which does not take place in normal cells and which also contributes to the inactivation of the PTEN.
“What happens is that there is inactivation of the PTEN by mechanisms that affect the activity of the protein. The final consequence is exactly the same as the genetic mutation of the PTEN: the activation of a tumour path, which takes place in the great majority of the cases of T leukaemia”, points out Ana Silva, first author of the work.
“With our results we also managed to reveal potential new therapeutic targets against T leukaemia. For example the use of pharmacological CK2 inhibitors might lead to the death of malign T cells without affecting the patients’ normal cells”, João Taborda Barata makes clear. This path might make it possible to diminish the side effects resulting from cancer treatments, such as chemotherapy, for example.
The Pfizer Prizes began in 1956, as a result of a partnership with the Lisbon Society of Medical Sciences (SCML), responsible for the assessing and choice of the award-winning works.
Cheila Almeida
Marta Agostinho (marta-elisa@fm.ul.pt)
Communication and Training Unit
Institute of Molecular Medicine
http://www.imm.ul.pt