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19 results on '"Dirks, P"'

1. macroH2A2 antagonizes epigenetic programs of stemness in glioblastoma

Author

Nikolic, Ana, Maule, Francesca, Bobyn, Anna, Ellestad, Katrina, Paik, Seungil, Marhon, Sajid A., Mehdipour, Parinaz, Lun, Xueqing, Chen, Huey-Miin, Mallard, Claire, Hay, Alexander J., Johnston, Michael J., Gafuik, Christopher J., Zemp, Franz J., Shen, Yaoqing, Ninkovic, Nicoletta, Osz, Katalin, Labit, Elodie, Berger, N. Daniel, Brownsey, Duncan K., Kelly, John J., Biernaskie, Jeff, Dirks, Peter B., Derksen, Darren J., Jones, Steven J. M., Senger, Donna L., Chan, Jennifer A., Mahoney, Douglas J., De Carvalho, Daniel D., and Gallo, Marco

Published
2023
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3. Host-diet-gut microbiome interactions influence human energy balance: a randomized clinical trial

Author

Karen D. Corbin, Elvis A. Carnero, Blake Dirks, Daria Igudesman, Fanchao Yi, Andrew Marcus, Taylor L. Davis, Richard E. Pratley, Bruce E. Rittmann, Rosa Krajmalnik-Brown, and Steven R. Smith

Subjects
Science
Abstract

Abstract The gut microbiome is emerging as a key modulator of human energy balance. Prior studies in humans lacked the environmental and dietary controls and precision required to quantitatively evaluate the contributions of the gut microbiome. Using a Microbiome Enhancer Diet (MBD) designed to deliver more dietary substrates to the colon and therefore modulate the gut microbiome, we quantified microbial and host contributions to human energy balance in a controlled feeding study with a randomized crossover design in young, healthy, weight stable males and females (NCT02939703). In a metabolic ward where the environment was strictly controlled, we measured energy intake, energy expenditure, and energy output (fecal and urinary). The primary endpoint was the within-participant difference in host metabolizable energy between experimental conditions [Control, Western Diet (WD) vs. MBD]. The secondary endpoints were enteroendocrine hormones, hunger/satiety, and food intake. Here we show that, compared to the WD, the MBD leads to an additional 116 ± 56 kcals (P 0.05). Microbial 16S rRNA gene copy number (a surrogate of biomass) increases (P

Published
2023
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4. macroH2A2 antagonizes epigenetic programs of stemness in glioblastoma

Author

Ana Nikolic, Francesca Maule, Anna Bobyn, Katrina Ellestad, Seungil Paik, Sajid A. Marhon, Parinaz Mehdipour, Xueqing Lun, Huey-Miin Chen, Claire Mallard, Alexander J. Hay, Michael J. Johnston, Christopher J. Gafuik, Franz J. Zemp, Yaoqing Shen, Nicoletta Ninkovic, Katalin Osz, Elodie Labit, N. Daniel Berger, Duncan K. Brownsey, John J. Kelly, Jeff Biernaskie, Peter B. Dirks, Darren J. Derksen, Steven J. M. Jones, Donna L. Senger, Jennifer A. Chan, Douglas J. Mahoney, Daniel D. De Carvalho, and Marco Gallo

Subjects
Science
Abstract

Abstract Self-renewal is a crucial property of glioblastoma cells that is enabled by the choreographed functions of chromatin regulators and transcription factors. Identifying targetable epigenetic mechanisms of self-renewal could therefore represent an important step toward developing effective treatments for this universally lethal cancer. Here we uncover an epigenetic axis of self-renewal mediated by the histone variant macroH2A2. With omics and functional assays deploying patient-derived in vitro and in vivo models, we show that macroH2A2 shapes chromatin accessibility at enhancer elements to antagonize transcriptional programs of self-renewal. macroH2A2 also sensitizes cells to small molecule-mediated cell death via activation of a viral mimicry response. Consistent with these results, our analyses of clinical cohorts indicate that high transcriptional levels of this histone variant are associated with better prognosis of high-grade glioma patients. Our results reveal a targetable epigenetic mechanism of self-renewal controlled by macroH2A2 and suggest additional treatment approaches for glioblastoma patients.

Published
2023
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5. The transcriptional landscape of Shh medulloblastoma.

Author

Skowron, Patryk, Farooq, Hamza, Cavalli, Florence MG, Morrissy, A Sorana, Ly, Michelle, Hendrikse, Liam D, Wang, Evan Y, Djambazian, Haig, Zhu, Helen, Mungall, Karen L, Trinh, Quang M, Zheng, Tina, Dai, Shizhong, Stucklin, Ana S Guerreiro, Vladoiu, Maria C, Fong, Vernon, Holgado, Borja L, Nor, Carolina, Wu, Xiaochong, Abd-Rabbo, Diala, Bérubé, Pierre, Wang, Yu Chang, Luu, Betty, Suarez, Raul A, Rastan, Avesta, Gillmor, Aaron H, Lee, John JY, Zhang, Xiao Yun, Daniels, Craig, Dirks, Peter, Malkin, David, Bouffet, Eric, Tabori, Uri, Loukides, James, Doz, François P, Bourdeaut, Franck, Delattre, Olivier O, Masliah-Planchon, Julien, Ayrault, Olivier, Kim, Seung-Ki, Meyronet, David, Grajkowska, Wieslawa A, Carlotti, Carlos G, de Torres, Carmen, Mora, Jaume, Eberhart, Charles G, Van Meir, Erwin G, Kumabe, Toshihiro, French, Pim J, Kros, Johan M, Jabado, Nada, Lach, Boleslaw, Pollack, Ian F, Hamilton, Ronald L, Rao, Amulya A Nageswara, Giannini, Caterina, Olson, James M, Bognár, László, Klekner, Almos, Zitterbart, Karel, Phillips, Joanna J, Thompson, Reid C, Cooper, Michael K, Rubin, Joshua B, Liau, Linda M, Garami, Miklós, Hauser, Peter, Li, Kay Ka Wai, Ng, Ho-Keung, Poon, Wai Sang, Yancey Gillespie, G, Chan, Jennifer A, Jung, Shin, McLendon, Roger E, Thompson, Eric M, Zagzag, David, Vibhakar, Rajeev, Ra, Young Shin, Garre, Maria Luisa, Schüller, Ulrich, Shofuda, Tomoko, Faria, Claudia C, López-Aguilar, Enrique, Zadeh, Gelareh, Hui, Chi-Chung, Ramaswamy, Vijay, Bailey, Swneke D, Jones, Steven J, Mungall, Andrew J, Moore, Richard A, Calarco, John A, Stein, Lincoln D, Bader, Gary D, Reimand, Jüri, Ragoussis, Jiannis, Weiss, William A, Marra, Marco A, Suzuki, Hiromichi, and Taylor, Michael D

Subjects
Humans, Medulloblastoma, Cerebellar Neoplasms, Signal Transduction, Gene Expression Regulation, Neoplastic, Adolescent, Adult, Middle Aged, Child, Child, Preschool, Infant, Female, Male, Hedgehog Proteins, Gene Regulatory Networks, Genetic Variation, Young Adult, Transcriptome, Pediatric Research Initiative, Brain Cancer, Pediatric, Rare Diseases, Genetics, Pediatric Cancer, Clinical Research, Brain Disorders, Neurosciences, Biotechnology, Human Genome, Cancer, 2.1 Biological and endogenous factors
Abstract

Sonic hedgehog medulloblastoma encompasses a clinically and molecularly diverse group of cancers of the developing central nervous system. Here, we use unbiased sequencing of the transcriptome across a large cohort of 250 tumors to reveal differences among molecular subtypes of the disease, and demonstrate the previously unappreciated importance of non-coding RNA transcripts. We identify alterations within the cAMP dependent pathway (GNAS, PRKAR1A) which converge on GLI2 activity and show that 18% of tumors have a genetic event that directly targets the abundance and/or stability of MYCN. Furthermore, we discover an extensive network of fusions in focally amplified regions encompassing GLI2, and several loss-of-function fusions in tumor suppressor genes PTCH1, SUFU and NCOR1. Molecular convergence on a subset of genes by nucleotide variants, copy number aberrations, and gene fusions highlight the key roles of specific pathways in the pathogenesis of Sonic hedgehog medulloblastoma and open up opportunities for therapeutic intervention.

Published
2021

6. A brain precursor atlas reveals the acquisition of developmental-like states in adult cerebral tumours

Author

Akram A. Hamed, Daniel J. Kunz, Ibrahim El-Hamamy, Quang M. Trinh, Omar D. Subedar, Laura M. Richards, Warren Foltz, Garrett Bullivant, Matthaeus Ware, Maria C. Vladoiu, Jiao Zhang, Antony M. Raj, Trevor J. Pugh, Michael D. Taylor, Sarah A. Teichmann, Lincoln D. Stein, Benjamin D. Simons, and Peter B. Dirks

Subjects
Science
Abstract

The link between neural development and tumourigenesis in adult glioma remains unclear. Here, the authors monitor the developmental stages of Sox2 + /− stem cells from a mouse model using single-cell RNA sequencing and suggest the acquisition of embryonic-like states in the adult glioma development.

Published
2022
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7. Single-cell chromatin profiling of the primitive gut tube reveals regulatory dynamics underlying lineage fate decisions

Author

Ryan J. Smith, Hongpan Zhang, Shengen Shawn Hu, Theodora Yung, Roshane Francis, Lilian Lee, Mark W. Onaitis, Peter B. Dirks, Chongzhi Zang, and Tae-Hee Kim

Subjects
Science
Abstract

The primitive gut tube gives rise to all major internal organs, while underlying regulatory mechanisms are unclear. Here, the authors analyze its chromatin landscape at the single-cell level and define the epigenetic regulation of lineage fate decisions and plasticity in organ development and homeostasis.

Published
2022
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11. The white matter is a pro-differentiative niche for glioblastoma

Author

Lucy J. Brooks, Melanie P. Clements, Jemima J. Burden, Daniela Kocher, Luca Richards, Sara Castro Devesa, Leila Zakka, Megan Woodberry, Michael Ellis, Zane Jaunmuktane, Sebastian Brandner, Gillian Morrison, Steven M. Pollard, Peter B. Dirks, Samuel Marguerat, and Simona Parrinello

Subjects
Science
Abstract

Glioma stem cells (GSCs) retain the ability to partially differentiate, but it is unclear how the brain microenvironment may influence this response. Here the authors show that glioblastoma cells infiltrating into the white matter acquire pre-oligodendrocyte-like fate in a process that mimics myelin repair and results in tumour suppression

Published
2021
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12. The transcriptional landscape of Shh medulloblastoma

Author

Patryk Skowron, Hamza Farooq, Florence M. G. Cavalli, A. Sorana Morrissy, Michelle Ly, Liam D. Hendrikse, Evan Y. Wang, Haig Djambazian, Helen Zhu, Karen L. Mungall, Quang M. Trinh, Tina Zheng, Shizhong Dai, Ana S. Guerreiro Stucklin, Maria C. Vladoiu, Vernon Fong, Borja L. Holgado, Carolina Nor, Xiaochong Wu, Diala Abd-Rabbo, Pierre Bérubé, Yu Chang Wang, Betty Luu, Raul A. Suarez, Avesta Rastan, Aaron H. Gillmor, John J. Y. Lee, Xiao Yun Zhang, Craig Daniels, Peter Dirks, David Malkin, Eric Bouffet, Uri Tabori, James Loukides, François P. Doz, Franck Bourdeaut, Olivier O. Delattre, Julien Masliah-Planchon, Olivier Ayrault, Seung-Ki Kim, David Meyronet, Wieslawa A. Grajkowska, Carlos G. Carlotti, Carmen de Torres, Jaume Mora, Charles G. Eberhart, Erwin G. Van Meir, Toshihiro Kumabe, Pim J. French, Johan M. Kros, Nada Jabado, Boleslaw Lach, Ian F. Pollack, Ronald L. Hamilton, Amulya A. Nageswara Rao, Caterina Giannini, James M. Olson, László Bognár, Almos Klekner, Karel Zitterbart, Joanna J. Phillips, Reid C. Thompson, Michael K. Cooper, Joshua B. Rubin, Linda M. Liau, Miklós Garami, Peter Hauser, Kay Ka Wai Li, Ho-Keung Ng, Wai Sang Poon, G. Yancey Gillespie, Jennifer A. Chan, Shin Jung, Roger E. McLendon, Eric M. Thompson, David Zagzag, Rajeev Vibhakar, Young Shin Ra, Maria Luisa Garre, Ulrich Schüller, Tomoko Shofuda, Claudia C. Faria, Enrique López-Aguilar, Gelareh Zadeh, Chi-Chung Hui, Vijay Ramaswamy, Swneke D. Bailey, Steven J. Jones, Andrew J. Mungall, Richard A. Moore, John A. Calarco, Lincoln D. Stein, Gary D. Bader, Jüri Reimand, Jiannis Ragoussis, William A. Weiss, Marco A. Marra, Hiromichi Suzuki, and Michael D. Taylor

Subjects
Science
Abstract

Sonic Hedgehog medulloblastoma (Shh-MB) comprises four subtypes each with distinct clinical traits. Here the authors characterize the genome, transcriptome, and methylome of Shh-MB subtypes, revealing a complex fusion landscape and the molecular convergence of MYCN and cAMP signaling pathways.

Published
2021
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13. PRMT5 inhibition disrupts splicing and stemness in glioblastoma

Author

Patty Sachamitr, Jolene C. Ho, Felipe E. Ciamponi, Wail Ba-Alawi, Fiona J. Coutinho, Paul Guilhamon, Michelle M. Kushida, Florence M. G. Cavalli, Lilian Lee, Naghmeh Rastegar, Victoria Vu, María Sánchez-Osuna, Jasmin Coulombe-Huntington, Evgeny Kanshin, Heather Whetstone, Mathieu Durand, Philippe Thibault, Kirsten Hart, Maria Mangos, Joseph Veyhl, Wenjun Chen, Nhat Tran, Bang-Chi Duong, Ahmed M. Aman, Xinghui Che, Xiaoyang Lan, Owen Whitley, Olga Zaslaver, Dalia Barsyte-Lovejoy, Laura M. Richards, Ian Restall, Amy Caudy, Hannes L. Röst, Zahid Quyoom Bonday, Mark Bernstein, Sunit Das, Michael D. Cusimano, Julian Spears, Gary D. Bader, Trevor J. Pugh, Mike Tyers, Mathieu Lupien, Benjamin Haibe-Kains, H. Artee Luchman, Samuel Weiss, Katlin B. Massirer, Panagiotis Prinos, Cheryl H. Arrowsmith, and Peter B. Dirks

Subjects
Science
Abstract

The arginine methyltransferase PRMT5 is over-expressed in cancer and has a role in the maintenance of stem cells. Here, the authors show that PRMT5 inhibitors can block the growth of patient derived glioblastoma stem cell cultures in vitro and in vivo, suggesting that PRMT5 inhibition may be a useful therapeutic strategy

Published
2021
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14. GLUT1 inhibition blocks growth of RB1-positive triple negative breast cancer

Author

Qin Wu, Wail ba-alawi, Genevieve Deblois, Jennifer Cruickshank, Shili Duan, Evelyne Lima-Fernandes, Jillian Haight, Seyed Ali Madani Tonekaboni, Anne-Marie Fortier, Hellen Kuasne, Trevor D. McKee, Hassan Mahmoud, Michelle Kushida, Sarina Cameron, Nergiz Dogan-Artun, WenJun Chen, Yan Nie, Lan Xin Zhang, Ravi N. Vellanki, Stanley Zhou, Panagiotis Prinos, Bradly G. Wouters, Peter B. Dirks, Susan J. Done, Morag Park, David W. Cescon, Benjamin Haibe-Kains, Mathieu Lupien, and Cheryl H. Arrowsmith

Subjects
Science
Abstract

Triple negative breast cancer is a deadly form of breast cancer with limited therapeutic options. Here the authors show the efficacy of GLUT1 pharmacological inhibition against a subset of tumors expressing RB1, thereby identifying RB1 protein level as a biomarker of sensitivity to anti-GLUT1 therapy.

Published
2020
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15. The white matter is a pro-differentiative niche for glioblastoma

Author

Brooks, Lucy J., Clements, Melanie P., Burden, Jemima J., Kocher, Daniela, Richards, Luca, Devesa, Sara Castro, Zakka, Leila, Woodberry, Megan, Ellis, Michael, Jaunmuktane, Zane, Brandner, Sebastian, Morrison, Gillian, Pollard, Steven M., Dirks, Peter B., Marguerat, Samuel, and Parrinello, Simona

Published
2021
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16. PRMT5 inhibition disrupts splicing and stemness in glioblastoma

Author

Sachamitr, Patty, Ho, Jolene C., Ciamponi, Felipe E., Ba-Alawi, Wail, Coutinho, Fiona J., Guilhamon, Paul, Kushida, Michelle M., Cavalli, Florence M. G., Lee, Lilian, Rastegar, Naghmeh, Vu, Victoria, Sánchez-Osuna, María, Coulombe-Huntington, Jasmin, Kanshin, Evgeny, Whetstone, Heather, Durand, Mathieu, Thibault, Philippe, Hart, Kirsten, Mangos, Maria, Veyhl, Joseph, Chen, Wenjun, Tran, Nhat, Duong, Bang-Chi, Aman, Ahmed M., Che, Xinghui, Lan, Xiaoyang, Whitley, Owen, Zaslaver, Olga, Barsyte-Lovejoy, Dalia, Richards, Laura M., Restall, Ian, Caudy, Amy, Röst, Hannes L., Bonday, Zahid Quyoom, Bernstein, Mark, Das, Sunit, Cusimano, Michael D., Spears, Julian, Bader, Gary D., Pugh, Trevor J., Tyers, Mike, Lupien, Mathieu, Haibe-Kains, Benjamin, Artee Luchman, H., Weiss, Samuel, Massirer, Katlin B., Prinos, Panagiotis, Arrowsmith, Cheryl H., and Dirks, Peter B.

Published
2021
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17. Miniaturised interaction proteomics on a microfluidic platform with ultra-low input requirements

Author

Cristina Furlan, René A. M. Dirks, Peter C. Thomas, Robert C. Jones, Jing Wang, Mark Lynch, Hendrik Marks, and Michiel Vermeulen

Subjects
Science
Abstract

Affinity purification-mass spectrometry (AP-MS) can identify endogenous protein interactions but the need for high amounts of input material still limits its applicability. Here, the authors present a microfluidic-based AP-MS workflow that can capture protein interactions from 50─100-fold less input material than conventional approaches.

Published
2019
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19. GLUT1 inhibition blocks growth of RB1-positive triple negative breast cancer

Author

Wu, Qin, ba-alawi, Wail, Deblois, Genevieve, Cruickshank, Jennifer, Duan, Shili, Lima-Fernandes, Evelyne, Haight, Jillian, Tonekaboni, Seyed Ali Madani, Fortier, Anne-Marie, Kuasne, Hellen, McKee, Trevor D., Mahmoud, Hassan, Kushida, Michelle, Cameron, Sarina, Dogan-Artun, Nergiz, Chen, WenJun, Nie, Yan, Zhang, Lan Xin, Vellanki, Ravi N., Zhou, Stanley, Prinos, Panagiotis, Wouters, Bradly G., Dirks, Peter B., Done, Susan J., Park, Morag, Cescon, David W., Haibe-Kains, Benjamin, Lupien, Mathieu, and Arrowsmith, Cheryl H.

Published
2020
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