Epigenetics

"Epigenetic alterations are reversible and therefore the genes that regulate them are interesting targets for the development of new therapeutic strategies against cancer".

DR. XABIER AGIRRE ENA
RESEARCHER. EPIGENETICS RESEARCH GROUP

Alterations in epigenetic and epitranscriptomic mechanisms play an important role in the development of different human tumors, including hematological malignancies. Deciphering these alterations, the genes that regulate them and their functional impact is key both to improve diagnosis/prognosis and to develop new therapeutic strategies to improve the treatment and response of patients with these hematological malignancies.

The research of our group focuses on the study of the cell biology of Multiple Myeloma and Acute Myeloid Leukemia by analyzing the alterations that occur in epigenetic mechanisms (such as DNA methylation or histone modifications), the transcriptome (both coding and non-coding) or in the epitranscriptome. All this with the aim of using this knowledge both to improve the prognosis of patients by identifying key biomarkers and to develop new therapeutic strategies based on Epi-PROTACs or therapies against RNA. This research is carried out thanks to a multidisciplinary teamwork and in close collaboration with leading research groups, both from our own center or other national or international centers.

Research carried out in the group has allowed us to define that the Multiple Myeloma cell is characterized by DNA hypermethylation in intronic enhancer regions embedded in extensive DNA hypomethylation; a de novo activation of enhancer regions and promoters that regulate the expression of genes essential for Multiple Myeloma development, and the expression of a large number of long non-coding RNAs that participate even in chimeric transcripts and that are essential for the proliferation of Multiple Myeloma cells. 

In turn, the research carried out has allowed us to focus on the design and development of epigenetic therapies, based on small molecules, against different epigenetic enzymes. We have developed a dual inhibitor against the methyltransferase activity of G9a and DNMTs that has shown great efficacy in different hematological neoplasms (acute leukemia, lymphoma or multiple myeloma) or solid tumors (bladder cancer or hepatocarcinoma); new deacetylase inhibitors that lead to differentiation of the Acute Myeloid Leukemia tumor cell through changes in the acetylation of non-histone proteins.

Dr. Xabier Agirre Ena

GROUP LEADER

+34 948 194 700 | Ext. 81 1002
xaguirre@unav.es
Perfil investigador

Objectives of the Epigenetics Research Group


To discover the alterations occurring at the epigenome, transcriptome and epitranscriptome level in Multiple Myeloma and Acute Myeloid Leukemia..

To deepen the role that alterations in the epigenome, transcriptome and epitranscriptome may have both at the biomarker level, functionality, both in vitro and in vivo, and as a therapeutic target in Multiple Myeloma or Acute Myeloid Leukemia cells.


To develop novel therapeutic strategies to improve the response and quality of life of patients with these hematological malignancies.

Identifying alterations in Multiple Myeloma

Our main objective is to identify the alterations that occur at the epigenome, non-coding transcriptome and epitranscriptome level in Multiple Myeloma and to know their implication in this neoplasm with the mission of designing new therapeutic strategies to improve the response and quality of life of patients.

Lines of research

PI: Xabier Agirre

Our overall objective is to study and understand in depth both the altered epigenome (DNA methylation and histone modifications) and the aberrant regulation of the enzymes that regulate epigenetic mechanisms and the epitrasncriptome (specifically the role of the m6A modification and its regulatory genes) in Multiple Myeloma (MM) tumor cells. This objective pursues the aim of better understanding the disease and detecting new targets, for the development of new therapeutic strategies for the treatment and improvement of the quality of life of these patients.
Objectives

  • To identify the epigenetic mechanisms that present alterations and the epigenetic enzymes deregulated in MM.
  • To study the role of transcription factors in epigenetic dysregulation.
  • To define the functionality of altered and essential epigenetic genes in MM.
  • To analyze the mechanisms that alter the expression of m6A genes in MM and to study the role they play as biomarkers to improve the stratification of patients with MM, their functionality and potential as therapeutic targets. 
  • Synthesize and validate new small molecules and/or PROTACs directed against epigenetic and epitranscriptomic targets for the treatment of MM or other tumor types.

PI: Xabier Agirre

The general objective of this project is to identify the lncRNAs that present a specific expression in tumor plasma cells of patients with MM and to know their dynamism of expression within the context of terminal differentiation of B cells. The aim of this study is on the one hand to study the functional role that these altered lncRNAs may play in the pathogenesis of MM and on the other hand the development of new therapeutic strategies against these altered RNA transcripts in MM.

Objectives

  • Identify the lncRNAs expressed and altered in MM.
  • Detection and functional studies of lncRNAs in MM.
  • To design new therapeutic strategies against RNA molecules.

PI: Xabier Agirre

The general objective of this line of research is to infer the alterations that the metabolism of MM and AML tumor cells may undergo, based on an analysis of the transcriptome of the genes involved in this metabolism. 

Objectives

  • To identify the alterations at the transcriptome level that genes related to metabolism in MM and AML may undergo.
  • To study the role of metabolic transcriptome alterations as a biomarker for the diagnosis/prognosis of patients with MM or AML.
  • To study the functionality of metabolic genes altered in MM or AML. 
  • To design and validate new therapeutic strategies against altered metabolic genes for the treatment of MM or AML.

Meet the research team

Scientific activity of the
Epigenetics Research Group