Our research focuses on understanding the epigenetic mechanisms underlying tumourigenesis and translating this knowledge into more efficient approaches for epigenetic therapy. We use a truly multi-disciplinary approach to investigate what mechanisms are driving the cancer-specific epigenetic alterations and to translate this knowledge into more efficient epigenetic interventions. To achieve this goal, we combine traditional molecular and cellular biology techniques with functional genomics screening, Next Generation Sequencing and computational biology.
Daniel De Carvalho
- Epigenetic reprogramming in cancerEpigenetic modifications are heritable, yet reversible, modifications that do not involve changes to the underlying DNA sequence. During the tumour development, extensive reprogramming of every component of the epigenetic machinery is observed. However, despite all the knowledge accumulated in the cancer epigenetics field, little is known about the pathways and the molecules involved in driving this epigenetic reprogramming.
- Epigenetic therapyA few drugs acting on DNA methyltransferase and histone deacetylase enzymes have already received FDA approval, providing validation that pharmacological alteration of epigenetic modifications has tangible clinical benefit. However, the current generation of epigenetic drugs acts by inhibiting chromatin-modifying enzymes and, consequently, has nonspecific, pan-genomic effects. This is associated with a significant dose-limiting toxicity. Our lab is trying to identify the molecules and pathways driving cancer-specific epigenetic modifications. We expect that future generations of cancer epigenetic therapies will target these driver molecules and pathways, instead of the core epigenetic machinery itself (that are necessary to establish and maintain the epigenetic landscape of normal cells). The identification of these drug targets will allow more rational cancer epigenetic therapies, with increased efficiency and with fewer risks associated with the reactivation of developmental genes.
Mutant IDH1 Downregulates ATM and Alters DNA Repair and Sensitivity to DNA Damage Independent of TET2.
Cancer Cell. 2016 Jul 9;
Oncoimmunology. 2016 Mar;5(3):e1090077
Oncotarget. 2016 Feb 19;
DNA-Demethylating Agents Target Colorectal Cancer Cells by Inducing Viral Mimicry by Endogenous Transcripts.
Cell. 2015 Aug 27;162(5):961-73
IL-17 promotes mammary tumor progression by changing the behavior of tumor cells and eliciting tumorigenic neutrophils recruitment.
Cancer Res. 2015 Jul 24;
Diacerein improves left ventricular remodeling and cardiac function by reducing the inflammatory response after myocardial infarction.
PLoS One. 2015;10(3):e0121842
Aberrant DNA methylation reprogramming during induced pluripotent stem cell generation is dependent on the choice of reprogramming factors.
Cell Regen (Lond). 2014;3(1):4
Cancer Cell. 2014 Oct 13;26(4):577-90
High-throughput DNA analysis shows the importance of methylation in the control of immune inflammatory gene transcription in chronic periodontitis.
Clin Epigenetics. 2014;6(1):15
Scientist, Princess Margaret Cancer Centre
Assistant Professor, Department of Medical Biophysics, University of Toronto