Our research focuses on understanding the epigenetic mechanisms  underlying tumorigenesis and the translation of this knowledge into more efficient approaches for epigenetic therapy. We use a truly multi-disciplinary approach to discover what mechanisms are driving the cancer-specific epigenetic alterations and to translate this knowledge towards application. To achieve this goal, we combine advanced molecular and cellular biology techniques with Next Generation Sequencing (NGS), epigenomics and computational biology.
  • Epigenetic therapy
    Epigenetic aberrations have been casually associated with cancer. Recent advancements in the rapidly evolving field of cancer epigenetics have shown extensive reprogramming of every component of the epigenetic machinery in cancer. Currently, drugs acting on DNA methyltransferase and histone deacetylase enzymes have already been FDA approved. This  provides validation that pharmacological alteration of chromatin modifications has tangible clinical benefit. A new generation of drugs acting on a broad range of epigentic enzymes that act as writers, erasers and readers of the epigenome are currently in clinical and pre-clinical evaluation. Our lab is interested in understanding their biological mechanism of action in the cancer cell and on the immune system.
  • Immunotherapy
    Studying the potential to modulate the immune response against tumor cells is one of the most rapidly moving and exciting areas in clinical oncology today. Over the last two decades, we have significantly improved our understanding of how the immune system interacts with cancer cells and how cancer can evade the immune response. This knowledge has led to the development of novel immunotherapy protocols, such as immune checkpoint blockade, with increasingly better clinical results. However, there is still a large proportion of patients that do not respond to cancer immunotherapy alone. Recent work from our lab suggests that DNA demethylating drugs can induce an innate immune activation on cancer  cells, a process we named ‘viral mimicry’. This process may prime cancer  cells for an immune response, highlighting the potential to combine epigenetic therapy with immunotherapy.
  • Cancer-initiating cells
    Many tumor types are organized as a cellular hierarchy sustained by a  subpopulation of cancer-initiating cells (CICs). These CICs possess unique features, including long-term self-renewal, the ability to initiate tumor growth in xenograft models, and the ability to  differentiate into the bulk of the tumor mass. CICs are believed to play a major role in tumor relapse and patient survival, suggesting that therapeutic strategies targeting this cell population would be highly  beneficial to patient outcome. Our lab recently published that DNA demethylating agents can target colorectal CICs, highlighting the potential use of epigenetic therapy to prevent tumor relapse.

Related Links

Lab Website
GCN2 drives macrophage and MDSC function and immunosuppression in the tumor microenvironment.
Sci Immunol. 2019 Dec 13;4(42):
Halaby MJ, Hezaveh K, Lamorte S, Ciudad MT, Kloetgen A, MacLeod BL, Guo M, Chakravarthy A, Medina TDS, Ugel S, Tsirigos A, Bronte V, Munn DH, Pugh TJ, De Carvalho DD, Butler MO, Ohashi PS, Brooks DG, McGaha TL
Methods to detect endogenous dsRNA induction and recognition.
Methods Enzymol. 2019;629:35-51
Ettayebi I, Yau HL, De Carvalho DD
The role of DNA-demethylating agents in cancer therapy.
Pharmacol Ther. 2019 Oct 15;:107416
Mehdipour P, Murphy T, De Carvalho DD
Pervasive H3K27 Acetylation Leads to ERV Expression and a Therapeutic Vulnerability in H3K27M Gliomas.
Cancer Cell. 2019 Sep 16;36(3):338-339
Krug B, De Jay N, Harutyunyan AS, Deshmukh S, Marchione DM, Guilhamon P, Bertrand KC, Mikael LG, McConechy MK, Chen CCL, Khazaei S, Koncar RF, Agnihotri S, Faury D, Ellezam B, Weil AG, Ursini-Siegel J, De Carvalho DD, Dirks PB, Lewis PW, Salomoni P,...
Heart defibrillation: relationship between pacing threshold and defibrillation probability.
Biomed Eng Online. 2019 Sep 13;18(1):96
Antoneli PC, Goulart JT, Bonilha I, de Carvalho DD, de Oliveira PX
Preparation of cfMeDIP-seq libraries for methylome profiling of plasma cell-free DNA.
Nat Protoc. 2019 Aug 30;:
Shen SY, Burgener JM, Bratman SV, De Carvalho DD
DNA methylation as a robust classifier of epithelial ovarian cancer.
Clin Cancer Res. 2019 Jul 23;:
Ishak CA, Lheureux S, De Carvalho DD
Correction to: Toward a comprehensive view of cancer immune responsiveness: a synopsis from the SITC workshop.
J Immunother Cancer. 2019 Jul 04;7(1):167
Bedognetti D, Ceccarelli M, Galluzzi L, Lu R, Palucka K, Samayoa J, Spranger S, Warren S, Wong KK, Ziv E, Chowell D, Coussens LM, De Carvalho DD, DeNardo DG, Galon J, Kaufman HL, Kirchhoff T, Lotze MT, Luke JJ, Minn AJ, Politi K, Shultz LD, Simon R,...
The Mitochondrial Transacylase, Tafazzin, Regulates AML Stemness by Modulating Intracellular Levels of Phospholipids.
Cell Stem Cell. 2019 Jun 06;24(6):1007
Seneviratne AK, Xu M, Aristizabal Henao JJ, Fajardo VA, Hao Z, Voisin V, Xu GW, Hurren R, Kim S, MacLean N, Wang X, Gronda M, Jeyaraju D, Jitkova Y, Ketela T, Mullokandov M, Sharon D, Thomas G, Chouinard-Watkins R, Hawley JR, Schafer C, Yau HL, Khuchua...
Toward a comprehensive view of cancer immune responsiveness: a synopsis from the SITC workshop.
J Immunother Cancer. 2019 May 22;7(1):131
Bedognetti D, Ceccarelli M, Galluzzi L, Lu R, Palucka K, Samayoa J, Spranger S, Warren S, Wong KK, Ziv E, Chowell D, Coussens LM, De Carvalho DD, DeNardo DG, Galon J, Kaufman HL, Kirchhoff T, Lotze MT, Luke JJ, Minn AJ, Politi K, Shultz LD, Simon R,...

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Senior Scientist, Princess Margaret Cancer Centre

Assistant Professor, Department of Medical Biophysics, University of Toronto