个人简介

Ph.D. (Doctor of Philosophy)

研究领域

Molecular Biology and Disease Genomics Proteomics and Bioinformatics

Cancer stem cells (CSCs) are rare cells required for tumor initiation and propagation in brain tumors. These cells are resistant to current therapies and constitute a reservoir that enables tumor recurrence. Our previous work has shown that CSCs are characterized by specific epigenomic states, which differentiate them from the other cells in the tumor bulk. Our goal is to define these CSC-specific epigenetic states and target them with next-generation epi-drugs. Project 1. We have previously shown that CSCs possess characteristic chromatin architecture determined by a few epigenetic regulators, including the histone variant H3.3. Disrupting this 3D chromatin structure causes cells to lose their "stemness" properties. We will use genome editing technologies to dissect the role of histone variants and chromatin architecture in determining CSC properties. Project 2. Our published work suggests that CSCs might have a special ability of eluding the patient's immune system. We will investigate the role of specific chromatin remodellers in enabling a cell to evade the immune system, using cutting-edge epigenomic techniques to look at nucleosome occupancy, chromatin openness and DNA methylation.

近期论文

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Gallo M*, Dirks PB* (2016) Global chromatin architecture defines functional cancer hierarchies. Cell Cycle 15: 2093-2094. 27247183. *Corresponding authors. Gallo M, Coutinho FJ, Vanner RJ, Gayden T, Mack SC, Murison A, Remke M, Li R, Takayama N, Desai K, Lee L, Lan X, Park NI, Barsyte-Lovejoy D, Smil D, Sturm D, Kushida M, Head R, Cusimano MD, Bernstein M, Clarke ID, Dick JE, Pfister SM, Rich JN, Arrowsmith CH, Taylor MD, Jabado N, Bazett-Jones D, Lupien M*, Dirks PB* (2015) MLL5 orchestrates a cancer self-renewal state by repressing the histone variant H3.3 and globally reorganizing chromatin. Cancer Cell 28: 1-15. PMID: 26626085. *Co-corresponding authors. Vanner RJ, Remke M, Gallo M, Selvadurai HJ, Coutinho FJ, Lee L, Kushida M, Head R, Morrissy S, Zhu X, Aviv T, Voisin V, Clarke ID, Li Y, Mungall AJ, Moore RA, Ma Y, Jones SJM, Marra MA, Malkin D, Northcott PA, Kool M, Pfister SM, Bader G, Hochedlinger K, Korshunov A, Taylor MD, Dirks PB (2014) Quiescent Sox2+ cells drive hierarchical growth and relapse in Sonic hedgehog subgroup medulloblastoma. Cancer Cell 26: 33-47. PMID: 24954133. Mack SC*, Witt H*, Piro RM, Gu L, Zuyderduyn S, Stütz AM, Wang X, Gallo M, Garzia L, Zayne K, Zhang X, Ramaswamy V, Jäger N, Jones DT, Sill M, Pugh TJ, Ryzhova M, Wani KM, Shih DJ, Head R, Remke M, Bailey SD, Zichner T, Faria CC, Barszczyk M, Stark S, Seker-Cin H, Hutter S, Johann P, Bender S, Hovestadt V, Tzaridis T, Dubuc AM, Northcott PA, Peacock J, Bertrand KC, Agnihotri S, Cavalli FM, Clarke I, Nethery-Brokx K, Creasy CL, Verma SK, Koster J, Wu X, Yao Y, Milde T, Sin-Chan P, Zuccaro J, Lau L, Pereira S, Castelo-Branco P, Hirst M, Marra MA, Roberts SS, Fults D, Massimi L, Cho YJ, Van Meter T, Grajkowska W, Lach B, Kulozik AE, von Deimling A, Witt O, Scherer SW, Fan X, Muraszko KM, Kool M, Pomeroy SL, Gupta N, Phillips J, Huang A, Tabori U, Hawkins C, Malkin D, Kongkham PN, Weiss WA, Jabado N, Rutka JT, Bouffet E, Korbel JO, Lupien M, Aldape KD, Bader GD, Eils R, Lichter P, Dirks PB, Pfister SM, Korshunov A**, Taylor MD** (2014) Epigenomic alterations define lethal CIMP positive ependymomas of infancy. Nature 506: 445-450. PMID: 24553142. *These authors contributed equally. **Co-corresponding authors. Kleinman CL, Gerges N, Papillon-Cavanagh S, Sin-Chan P, Pramatarova A, Khuong Quang D-A, Adoue V, Busche S, Caron M, Djambazian H, Bemmo A, Fontebasso AM, Spence T, Schwartzentruber J, Albrecht S, Hauser P, Garami M, Klekner A, Bognar L, Montes J-L, Staffa A, Montpetit A, Berube, P, Zakrzewska M, Zakrzewski K, Liberski PP, Dong Z, Siegel PM, Duchaine T, Perotti C, Fleming A, Faury D, Remke M, Gallo M, Dirks P, Taylor MD, Sladek R, Pastinen T, Chan JA, Huang A, Majewski J, Jabado N (2014) Fused transcripts of TTYH1 and the C19MC microRNA cluster reawaken expression of an early development brain-specific DNMT3B and characterize the embryonal brain tumour ETMR. Nature Genetics 46: 39-44. PMID: 24316981. Gallo M, Ho J, Coutinho FJ, Vanner R, Lee L, Head R, Ling EKM, Clarke ID, Dirks PB (2013) A tumorigenic MLL-Homeobox network in human glioblastoma stem cells. Cancer Research 73: 417-427. PMID: 23108137.