Throughout my research career, I have focused on studying epigenetic dysregulation, especially its importance in cancer development and treatment. I earned my PhD in 2016 from the University of Milan in collaboration with SEMM, European School of Molecular Medicine, and then joined Dr. De Carvalho’s lab at the University Health Network (UHN), Princess Margaret Cancer Centre in Toronto to pursue my postdoctoral study. In October 2021, I joined the Ludwig Institute for Cancer Research at the University of Oxford to start my own independent research programme.
The Mehdipour research group at Ludwig Oxford seeks to:
- Study the translational role of immunogenic double-stranded RNAs (dsRNAs) as biomarkers for predicting and monitoring the response of cancer cells to cancer therapies.
- Understand the mechanisms by which the mammalian innate immune system discriminates endogenous from exogenous nucleic acids and exploit this to improve the cancer treatment.
- Identify novel candidates for therapeutic targeting in cancer.
Many research efforts focus largely on the DNA coding sequences, but the majority of the human genome is composed of dormant repeat elements that are evolutionary conserved. In my post-doctoral research, we found that DNA hypomethylating agents induce dsRNAs transcribed from SINE repeat elements (specifically, inverted Alus). These accumulated dsRNAs are immunogenic: mimicking viral dsRNAs, they bind to a pattern recognition receptor (such as MDA5) and activate the innate immune system, which fights against cancer cells. This was a crucial finding for understanding how epigenetic therapy induces viral mimicry in cancer cells. We also found that inhibition of the adenosine deaminase ADAR1 synergises with DNA hypomethylating agents in induction of innate immune responses.
My lab is exploring new ways in which epigenetic regulation and RNA modifications can be exploited to improve cancer treatment.
PRMT inhibition induces a viral mimicry response in triple-negative breast cancer.
Wu Q. et al, (2022), Nature chemical biology, 18, 821 - 830
The next generation of DNMT inhibitors
Mehdipour P. et al, (2021), Nature Cancer, 2, 1000 - 1001
DNA hypomethylating agents increase activation and cytolytic activity of CD8+ T cells
Loo Yau H. et al, (2021), Molecular Cell, 81, 1469 - 1483.e8
Epigenetic therapy induces transcription of inverted SINEs and ADAR1 dependency
Mehdipour P. et al, (2020), Nature, 588, 169 - 173
The role of DNA-demethylating agents in cancer therapy
Mehdipour P. et al, (2020), Pharmacology & Therapeutics, 205, 107416 - 107416