Our research focuses on the causes of resistance to endocrine therapies and the epigenetic basis of breast cancer. We use genomics techniques such as ChIPseq/MNaseI-seq and DHS-seq to study chromatin-transcription factors interactions. Currently, the lab is involved in 3 leading projects:
Role of non-coding mutations in breast cancer biology
Sung-Pil Hong, Neil Slaven, Seham Al-Shehri, Giacomo Corleone, Luca Magnani
The genome is vast and mostly under-explored. 95% of the genome does not code for genes but accumulate the majority of the mutations in cancers. One key focus of the lab is to systematically address the functional role of non-coding mutations in cancer. Recent work highlighted the role of noncoding regulatory regions in keeping the chromatin structure organized in discrete domains (topologically associating domain, TAD). TADs are highly enriched for the CTCF protein, which acts as insulator and enhancer facilitator element. Somatic regulatory mutations (SRMs) in breast cancer might alter CTCF binding affinity and reprogram the topological organization of cancer cells. Topological reprogramming might lead to favorable transcriptional programs and might be selected during tumor initiation or progression. In addition, recent studies showed that the transcription factor ZNF143 might be involved in gene expression by regulating in long-distance chromatin looping factors. The goal of this project is to investigate the involvement of ZNF143 and CTCF in chromatin looping in breast cancer and determine whether non-coding mutations on their binding site may promote the carcinogenesis.
Targeting cholesterol biosynthesis in breast cancer
Ylenia Perone, Luca Magnani
We have recently demonstrated that breast cancer cells adapt to therapy by turning on many biochemical pathways. Cholesterol biosynthesis was specifically activated in cells that acquire resistance to aromatase inhibitors, one of the major therapeutics for luminal breast cancer. This project will investigate how cholesterol biosynthesis is actually activated in these cell at the molecular level. This will reveal new strategies to antagonize the growth of drug-resistant breast cancer cells.
Epigenetic annotation of the breast cancer genome
Darren K Patten, Giacomo Corleone, Luca Magnani
The non-coding genome can be interpreted by using epigenetic annotations. Doing so, we can identify potential regulatory regions and gain a better understanding of the regulatory networks that drive gene expression in breast cancer. However, each cell type has its own epigenome (while each cell in the body shares essentially the same genome). We have now investigated the epigenome of more than 50 breast cancer patients. These data will help understanding how the epigenome influence breast cancer growth and progression.