Daniel De Carvalho

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
Epigenetic regulation of nitric oxide synthase 2, inducible (Nos2) by NLRC4 inflammasomes involves PARP1 cleavage.
Sci Rep. 2017 Feb 02;7:41686
Buzzo CL, Medina T, Branco LM, Lage SL, Ferreira LC, Amarante-Mendes GP, Hottiger MO, De Carvalho DD, Bortoluci KR
Early-life antibiotic treatment enhances the pathogenicity of CD4+ T cells during intestinal inflammation.
J Leukoc Biol. 2016 Dec 29;:
Scheer S, Medina TS, Murison A, Taves MD, Antignano F, Chenery A, Soma KK, Perona-Wright G, Lupien M, Arrowsmith CH, De Carvalho DD, Zaph C
Integrated (epi)-Genomic Analyses Identify Subgroup-Specific Therapeutic Targets in CNS Rhabdoid Tumors.
Cancer Cell. 2016 Dec 12;30(6):891-908
Torchia J, Golbourn B, Feng S, Ho KC, Sin-Chan P, Vasiljevic A, Norman JD, Guilhamon P, Garzia L, Agamez NR, Lu M, Chan TS, Picard D, de Antonellis P, Khuong-Quang DA, Planello AC, Zeller C, Barsyte-Lovejoy D, Lafay-Cousin L, Letourneau L, Bourgey M,...
Mutant IDH1 Downregulates ATM and Alters DNA Repair and Sensitivity to DNA Damage Independent of TET2.
Cancer Cell. 2016 Jul 9;
Inoue S, Li WY, Tseng A, Beerman I, Elia AJ, Bendall SC, Lemonnier F, Kron KJ, Cescon DW, Hao Z, Lind EF, Takayama N, Planello AC, Shen SY, Shih AH, Larsen DM, Li Q, Snow BE, Wakeham A, Haight J, Gorrini C, Bassi C, Thu KL, Murakami K, Elford AR, Ueda...
Pharmacological DNA demethylation: Implications for cancer immunotherapy.
Oncoimmunology. 2016 Mar;5(3):e1090077
Roulois D, Yau HL, De Carvalho DD
Pre-neoplastic epigenetic disruption of transcriptional enhancers in chronic inflammation.
Oncotarget. 2016 Feb 19;
Planello AC, Singhania R, Kron KJ, Bailey SD, Roulois D, Lupien M, Line SR, de Souza AP, De Carvalho DD
DNA-Demethylating Agents Target Colorectal Cancer Cells by Inducing Viral Mimicry by Endogenous Transcripts.
Cell. 2015 Aug 27;162(5):961-73
Roulois D, Loo Yau H, Singhania R, Wang Y, Danesh A, Shen SY, Han H, Liang G, Jones PA, Pugh TJ, O'Brien C, De Carvalho DD
IL-17 promotes mammary tumor progression by changing the behavior of tumor cells and eliciting tumorigenic neutrophils recruitment.
Cancer Res. 2015 Jul 24;
Benevides L, da Fonseca DM, Donate PB, Tiezzi DG, de Carvalho DD, de Andrade JM, Martins GA, da Silva JS
Diacerein improves left ventricular remodeling and cardiac function by reducing the inflammatory response after myocardial infarction.
PLoS One. 2015;10(3):e0121842
Torina AG, Reichert K, Lima F, de Souza Vilarinho KA, de Oliveira PP, do Carmo HR, de Carvalho DD, Saad MJ, Sposito AC, Petrucci O
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
Planello AC, Ji J, Sharma V, Singhania R, Mbabaali F, Müller F, Alfaro JA, Bock C, De Carvalho DD, Batada NN

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Scientist, Princess Margaret Cancer Centre

Assistant Professor, Department of Medical Biophysics, University of Toronto