Functional genomics and system biology approaches to define radiation response signatures

Project Code: 

Precision medicine holds the promise that the treatment of cancer will be based on individual assessment of risk and selection of optimal therapy. On the other hand, there is an increasing body of evidence to suggest that molecular and genomic differences can affect the response to radiation, and thus the outcome of therapy.

The aim of this project is to elucidate the pathways affecting the response to radiation in different cancer types and under different tumor microenvironmental conditions, and to question how these pathways might be altered with drug combinations to improve efficacy of radiotherapy.

The project will generate high-throughput genomics and transcriptomics data in a panel of cancer cell lines, and will analyse data from in vivo models and samples from large clinical cohorts. Using advanced computational and bioinformatics approaches developed in our lab (see references below) we will integrate these data, and will investigate how the genetic and molecular characteristics of the cancer and its surrounding microenvironment determine the response to radiation.

  1. Haider S, McIntyre A, van Stiphout RG, Winchester LM, Wigfield S, Harris AL, Buffa FM. Genomic alterations underlie a pan-cancer metabolic shift associated with tumour hypoxia. Genome Biol. 2016 Jun 29;17(1):140. PMID: 27358048
  2. Masiero M, Simões FC, Han HD, Snell C, Peterkin T, Bridges E, Mangala LS, Wu SY, Pradeep S, Li D, Han C, Dalton H, Lopez-Berestein G, Tuynman JB, Mortensen N, Li JL, Patient R, Sood AK, Banham AH, Harris AL, Buffa FM. A core human primary tumor angiogenesis signature identifies the endothelial orphan receptor ELTD1 as a key regulator of angiogenesis. Cancer Cell. 2013 Aug 12;24(2):229-41. PMID: 23871637
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