Welcome to Leonardo A. Meza-Zepeda's project group

Mesenchymal Genomics

 

Proliferation and differentiation programs are highly controlled processes at the genetic and epigenetic level. Using the state of the art high-throughput technologies our group studies genome-wide and gene-centric events that govern mesenchymal biology in health and disease. Our work can be divided in two main areas of research:

Integrated analysis of genetic and epigenetic changes of human sarcomas
Using an integrative approach, we are unveiling pathways and transcriptional and gene networks in osteosarcomas (bone tumours) and the way these are controlled. Using different EuroBoNeT (European Network of Excellence for Bone Tumours) preclinical osteosarcoma panels (cell lines and xenografts) and a panel of normal controls, we are integrating mRNA and miRNA expression, DNA copy number and methylation data genome-wide. The combination of different levels of genome-wide data makes it possible to identify and explore interdependencies between genes and genetic and epigenetic events, as well as to identify recurrent pathways and gene networks that are altered in osteosarcomas. Preliminary work has identified specific pathways frequently targeted for inactivation by genetic and epigenetic alterations i.e. miRNA deregulation, amplifications and deletions, as well as CpG island methylation. Our analysis has identified the importance of epigenetic silencing in controlling gene expression.
The identified pathways, networks and regulatory genes will be validated using the EuroBoNeT panel of osteosarcomas clinical samples, and correlations between the molecular data and clinical variables will be investigated.

Genetic and epigenetic networks of mesenchymal stem cell differentiation
The progression from a stem cell state to a more differentiated progeny is determined by the specific activation of transcriptional programs, as a consequence of orchestrated epigenetic and genetic events. Our work aims to identify and characterise transcriptional programs active during osteogenic and adipogenic differentiation of mesenchymal stem cells. This information will help to better understand the balance between stemness and differentiation and its deregulation in cancer.
Using a telomerase-immortalised bone marrow derived mesenchymal stem cell line model, we study the differentiation process towards the osteogenic and adipogenic lineage. To better understand stemness and differentiation at the molecular and cellular level, different types of genome-wide data, i.e. chromatin remodeling, DNA methylation and expression data are being integrated to identify transcriptional and epigenetic networks that are activated and silenced during differentiation. The information gathered from osteogenic differentiation will be associated to gene networks active in osteosarcomas to molecularly categorise osteosarcomas based on their differentiation stage (molecular staging).
Using a genome-wide integrative approach, we aim to better understand transcriptional networks in mesenchymal stem cell biology, differentiation and malignant transformation of bone.

I'm also head of the Helse Sør-Øst and University of Oslo Microarray and Sequecing Core Facility