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IL-7/IL-7R signaling networks in health and malignancy

Objective

Deregulation of signal transduction is a feature of tumor cells and signaling therapies are gaining importance in the growing arsenal against cancer. However, their full potential can only be achieved once we overcome the limited knowledge on how signaling networks are wired in cancer cells. Interleukin 7 (IL7) and its receptor (IL7R) are essential for normal T-cell development and function. However, they can also promote autoimmunity, chronic inflammation and cancer. We showed that patients with T-cell acute lymphoblastic leukemia (T-ALL), an aggressive hematological cancer, can display IL7R gain-of-function mutations leading to downstream signaling activation and cell transformation. Despite the biological relevance of IL7 and IL7R, the characterization of their signaling effectors remains limited. Here, we propose to move from the single molecule/pathway-centered analysis that has characterized the research on IL7/IL7R signaling, into a ‘holistic’ view of the IL7/IL7R signaling landscape. To do so, we will employ a multidisciplinary strategy, in which data from complementary high throughput analyses, informing on different levels of regulation of the IL7/IL7R signaling network, will be integrated via a systems biology approach, and complemented by cell and molecular biology experimentation and state-of-the-art in vivo models. The knowledge we will generate should have a profound impact on the understanding of the fundamental mechanisms by which IL7/IL7R signaling promotes leukemia and reveal novel targets for fine-tuned therapeutic intervention in T-ALL. Moreover, the scope of insights gained should extend beyond leukemia. Our in-depth, systems-level characterization of IL7/IL7R signaling will constitute a platform with extraordinary potential to illuminate the molecular role of the IL7/IL7R axis in other cancers (e.g. breast and lung) and pathological settings where IL7 has been implicated, such as HIV infection, multiple sclerosis and rheumatoid arthritis.

Field of science

  • /natural sciences/biological sciences/genetics and heredity/mutation
  • /natural sciences/biological sciences/molecular biology
  • /medical and health sciences/basic medicine/neurology/multiple sclerosis
  • /medical and health sciences/clinical medicine/oncology/cancer
  • /medical and health sciences/clinical medicine/oncology/leukemia
  • /medical and health sciences/clinical medicine/oncology/cancer/breast cancer

Call for proposal

ERC-2014-CoG
See other projects for this call

Funding Scheme

ERC-COG - Consolidator Grant

Host institution

INSTITUTO DE MEDICINA MOLECULAR JOAO LOBO ANTUNES
Address
Avenida Prof Egas Moniz
1649 028 Lisboa
Portugal
Activity type
Research Organisations
EU contribution
€ 1 988 125

Beneficiaries (1)

INSTITUTO DE MEDICINA MOLECULAR JOAO LOBO ANTUNES
Portugal
EU contribution
€ 1 988 125
Address
Avenida Prof Egas Moniz
1649 028 Lisboa
Activity type
Research Organisations