Leukemia and immuno-oncology
Josep Carreras Leukaemia Research Institute
Can Ruti Campus - Ctra de Can Ruti, Camí de les Escoles s/n
08916 Badalona, Barcelona
Our research is focused on the study of the molecular mechanisms driving leukemogenesis and on the identification of new therapeutic targets that can potentially translate into novel strategies for the treatment of leukemia patients. More specifically, one of our main interests is to identify and characterize non-coding genetic alterations that can induce aberrant enhancer activity, and function as drivers of leukemia transformation or contribute to leukemia progression through other means.
In addition, we are interested on the specific role of the immune system in developing antitumor responses. In particular, we will focus on the molecular characterization of the beneficial and deleterious responses induced by the use of immune-checkpoint inhibitors for the treatment of different tumor types.
1) Molecular pathways and targeted therapies in Juvenile Myelomonocytic Leukemia (JMML)
Juvenile myelomonocytic leukemia (JMML) is a pediatric myeloproliferative disorder characterized by the constitutive activation of the RAS signaling pathway. Most of the patients with JMML experience an aggressive clinical course of the disease and require hematopoietic stem cell transplantation (HSCT), which is currently the only therapeutic option to achieve long-term remission. However, this treatment entails a significant risk of transplant-related mortality in these patients and still, the overall survival at five years remains at 64%. In spite of the progresses made in the last years on the genetic and epigenetic characterization of JMML, this disease is still a clinical challenge due to its heterogeneity, difficult diagnosis, poor prognosis and the lack of alternative treatment options other than HSCT.
Our overarching goal is to integrate different methods in epigenetics, systems biology, functional genomics and biochemistry to address critical questions about the origin and progression of JMML, and to identify new therapeutic targets for the treatment of this disease. The specific aims of our research are:
- To establish a JMML working group in Spain and create a centralized JMML sample repository.
- To develop a comprehensive molecular analysis of JMML patients to define accurate diagnostic and stratification criteria and identify new potential therapeutic targets.
- To develop molecular- and cell-based therapies for the treatment of JMML.
2) Molecular mechanisms driving immune checkpoint inhibitor (ICI) antitumoral and toxic effects
The immune system is regulated by a number of inhibitory pathways that are essential to maintain self-tolerance and prevent immune-mediated tissue damage. During tumor progression, cancer cells develop strategies that allow them to hijack these immunological checkpoints in order to evade immune attack. Therapies based on immune checkpoint inhibitors (ICIs) targeting immune-escape mechanisms have been a major breakthrough for cancer treatment and are currently being used in a broad range of tumor types. However, immune deregulation in the context of ICI therapies is frequently associated with the development of immune-related adverse events (irAEs), a wide espectrum of autoimmune toxicities that in some cases result in premature termination of the therapy and that can be fatal in a low but significant proportion of the patients.
Here, we will integrate different methods in immunology, genetics, molecular biology and functional genomics to dissect the mechanisms that control therapeutic and adverse ICI-driven immune responses. Our specific aims are:
- To characterize the distinct molecular cues that govern anti-tumor and autoimmune responses induced by ICI immunotherapy.
- To identify and validate immune modulators as therapeutic targets to maximize the antitumor activity of ICIs while minimizing their acute and long term toxic side effects.
2019 Early Career International Award
(European School of Haematology)
2019 Acute Leukemia Forum Young Investigator Award
2018 ASH Abstract Achievement Award
(American Society of Hematology)
2011 VI Biogen-Idec Award for Young Investigators
|Laura Belver||Group Leaderfirstname.lastname@example.org|
|Claudia Fiñana Oroñez||PhD Studentemail@example.com|
|Noel Gómez Molina||PhD Studentfirstname.lastname@example.org|
|Sandra Alonso Moreno||Technicianemail@example.com|
|Anna Campagnari||Research Assistantfirstname.lastname@example.org|
|Anastasiia Novikova||Lab Technicianemail@example.com|
RHOA G17V Induces T Follicular Helper Cell Specification and Promotes LymphomagenesisCancer Cell. 2018; 33, 259-273. , .
The genetics and mechanisms of T-cell acute lymphoblastic leukemiaNat Rev Cancer. 2016; 16, 494-507. , .
Non-coding recurrent mutations in chronic lymphocytic leukaemiaNature. 2015; 526, 519-524 , .
Metabolic reprogramming induces resistance to anti-NOTCH1 therapies in T cell acute lymphoblastic leukemiaNat Med. 2015; 21, 1182-1189. , .
|Project leader:||Laura Belver|