Daniel De Carvalho

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.
  • Epigenetic reprogramming in cancer
    Epigenetic 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 therapy
    A 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.

Related Links

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...
Oncoimmunology. 2016 Mar;5(3):e1090077
Roulois D, Yau HL, De Carvalho DD
Oncotarget. 2016 Feb 19;
Planello AC, Singhania R, Kron KJ, Bailey SD, Roulois D, Lupien M, Line SR, de Souza AP, De Carvalho DD
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
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
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
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
Cancer Cell. 2014 Oct 13;26(4):577-90
Yang X, Han H, De Carvalho DD, Lay FD, Jones PA, Liang G
PLoS One. 2014;9(6):e99484
Fukumasu H, Rochetti AL, Pires PR, Silva ER, Mesquita LG, Strefezzi RF, De Carvalho DD, Dagli ML



Assistant Professor, Department of Medical Biophysics, University of Toronto