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Your search keyword '"Darman, Rachel"' showing total 9 results
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9 results on '"Darman, Rachel"'

2. H3B-8800, an orally available small-molecule splicing modulator, induces lethality in spliceosome-mutant cancers

Author

Seiler, Michael, Yoshimi, Akihide, Darman, Rachel, Chan, Betty, Keaney, Gregg, Thomas, Michael, Agrawal, Anant A, Caleb, Benjamin, Csibi, Alfredo, Sean, Eckley, Fekkes, Peter, Karr, Craig, Klimek, Virginia, Lai, George, Lee, Linda, Kumar, Pavan, Lee, Stanley Chun-Wei, Liu, Xiang, Mackenzie, Crystal, Meeske, Carol, Mizui, Yoshiharu, Padron, Eric, Park, Eunice, Pazolli, Ermira, Peng, Shouyong, Prajapati, Sudeep, Taylor, Justin, Teng, Teng, Wang, John, Warmuth, Markus, Yao, Huilan, Yu, Lihua, Zhu, Ping, Abdel-Wahab, Omar, Smith, Peter G, and Buonamici, Silvia

Subjects
RNA splicing -- Health aspects, Gene mutation -- Health aspects, Carcinogenesis -- Genetic aspects, Biological sciences, Health
Abstract

Author(s): Michael Seiler [1]; Akihide Yoshimi [2]; Rachel Darman [1]; Betty Chan [1]; Gregg Keaney [1]; Michael Thomas [1]; Anant A Agrawal [1]; Benjamin Caleb [1]; Alfredo Csibi [1]; Eckley [...]

Published
2018
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3. Cancer-Associated SF3B1 Hotspot Mutations Induce Cryptic 3′ Splice Site Selection through Use of a Different Branch Point

Author

Darman, Rachel B., Seiler, Michael, Agrawal, Anant A., Lim, Kian H., Peng, Shouyong, Aird, Daniel, Bailey, Suzanna L., Bhavsar, Erica B., Chan, Betty, Colla, Simona, Corson, Laura, Feala, Jacob, Fekkes, Peter, Ichikawa, Kana, Keaney, Gregg F., Lee, Linda, Kumar, Pavan, Kunii, Kaiko, MacKenzie, Crystal, Matijevic, Mark, Mizui, Yoshiharu, Myint, Khin, Park, Eun Sun, Puyang, Xiaoling, Selvaraj, Anand, Thomas, Michael P., Tsai, Jennifer, Wang, John Y., Warmuth, Markus, Yang, Hui, Zhu, Ping, Garcia-Manero, Guillermo, Furman, Richard R., Yu, Lihua, Smith, Peter G., and Buonamici, Silvia

Published
2015
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4. Abstract 1185: H3B-8800, a novel orally available SF3b modulator, shows preclinical efficacy across spliceosome mutant cancers

Author

Buonamici, Silvia, primary, Yoshimi, Akihide, additional, Thomas, Michael, additional, Seiler, Michael, additional, Chan, Betty, additional, Caleb, Benjamin, additional, Csibi, Fred, additional, Darman, Rachel, additional, Fekkes, Peter, additional, Karr, Craig, additional, Keaney, Gregg, additional, Kim, Amy, additional, Klimek, Virginia, additional, Kumar, Pavan, additional, Kunii, Kaiko, additional, Lee, Stanley Chun-Wei, additional, Liu, Xiang, additional, MacKenzie, Crystal, additional, Meeske, Carol, additional, Mizui, Yoshiharu, additional, Padron, Eric, additional, Park, Eunice, additional, Pazolli, Ermira, additional, Prajapati, Sudeep, additional, Rioux, Nathalie, additional, Taylor, Justin, additional, Wang, John, additional, Warmuth, Markus, additional, Yao, Huilan, additional, Yu, Lihua, additional, Zhu, Ping, additional, Abdel-Wahab, Omar, additional, and Smith, Peter, additional

Published
2017
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5. H3B-8800, an Orally Bioavailable Modulator of the SF3b Complex, Shows Efficacy in Spliceosome-Mutant Myeloid Malignancies

Author

Buonamici, Silvia, primary, Yoshimi, Akihide, additional, Thomas, Michael, additional, Seiler, Michael, additional, Chan, Betty, additional, Caleb, Benjamin, additional, Darman, Rachel, additional, Fekkes, Peter, additional, Karr, Craig, additional, Keaney, Gregg F., additional, Klimek, Virginia M., additional, Kunii, Kaiko, additional, Lee, Linda, additional, Lee, Stanley Chun-Wei, additional, Liu, Xiang, additional, Meeske, Carol, additional, Mizui, Yoshiharu, additional, Padron, Eric, additional, Park, Eunice, additional, Pazolli, Ermira, additional, Prajapati, Sudeep, additional, Taylor, Justin, additional, Wang, John, additional, Warmuth, Markus, additional, Yu, Lihua, additional, Zhu, Ping, additional, Abdel-Wahab, Omar, additional, and Smith, Peter G, additional

Published
2016
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6. Heterozygous Hotspot SF3B1 Mutations Found in Myelodysplastic Syndromes Downregulate Genes Involved in Differentiation of Erythroid Cells

Author

Buonamici, Silvia, primary, Darman, Rachel, additional, Perino, Samantha, additional, Agrawal, Anant, additional, Peng, Shouyong, additional, Seiler, Michael, additional, Lim, Kian Huat, additional, Bhavsar, Erica B., additional, Feala, Jacob, additional, Obeng, Esther A., additional, Bailey, Suzanna, additional, Chan, Betty, additional, Fekkes, Peter, additional, Keaney, Gregg F., additional, Kumar, Pavan, additional, Kunii, Kaiko, additional, Lee, Linda, additional, Mackenzie, Crystal, additional, Matijevic, Mark, additional, Mizui, Yoshiharu, additional, Myint, Khin, additional, Park, Eunice, additional, Pazolli, Ermira, additional, Thomas, Michael, additional, Wang, John, additional, Warmuth, Markus, additional, Yu, Lihua, additional, Zhu, Ping, additional, Furman, Richard R., additional, Ebert, Benjamin L, additional, and Smith, Peter G, additional

Published
2015
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7. Abstract B125: Mutant SF3B1 downregulates proteins involved in differentiation, including ABCB7

Author

Darman, Rachel B., primary, Perino, Samantha A., additional, Seiler, Michael, additional, Peng, Shouyong, additional, Feala, Jacob, additional, Fekkes, Peter, additional, Keaney, Gregg F., additional, Kunii, Kaiko, additional, Lee, Linda, additional, Lim, Kian Huat, additional, Oda, Yoshiya, additional, Myint, Khin, additional, Obeng, Esther A., additional, Pazolli, Ermira, additional, Park, Eun Sun, additional, Wang, John Yuan, additional, Warmuth, Markus, additional, Yu, Lihua, additional, Zhu, Ping, additional, Mizui, Yoshiharu, additional, Ebert, Benjamin L., additional, Smith, Peter G., additional, and Buonamici, Silvia, additional

Published
2015
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8. Abstract 2040: Mutations in SF3B1 lead to aberrant splicing through cryptic 3′ splice site selection and impair hematopoietic cell differentiation

Author

Buonamici, Silvia, primary, Perino, Samantha, additional, Lim, Kian Huat, additional, Feala, Jacob, additional, Darman, Rachel, additional, Obeng, Esther, additional, Furman, Richard R., additional, Bailey, Suzanna, additional, Keaney, Gregg, additional, Kumar, Pavan, additional, Mizui, Yoshiharu, additional, Park, Eunice, additional, Wang, John, additional, Warmuth, Markus, additional, Yu, Lihua, additional, Zhu, Ping, additional, Ebert, Benjamin L., additional, and Smith, Peter, additional

Published
2015
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9. The R882H DNMT3A hot spot mutation stabilizes the formation of large DNMT3A oligomers with low DNA methyltransferase activity.

Author

Tuong-Vi Nguyen, Shihua Yao, Yahong Wang, Rolfe, Alan, Selvaraj, Anand, Darman, Rachel, Jiyuan Ke, Warmuth, Markus, Smith, Peter G., Larsen, Nicholas A., Lihua Yu, Ping Zhu, Fekkes, Peter, Vaillancourt, Frédéric H., and Bolduc, David M.

Subjects
*MUTANT proteins, *HEMATOPOIETIC stem cells, *DNA methyltransferases, *OLIGOMERS, *CATALYTIC domains, *CELL differentiation
Abstract

DNMT3A (DNA methyltransferase 3A) is a de novo DNA methyltransferase responsible for establishing CpG methylation patterns within the genome. DNMT3A activity is essential for normal development, and its dysfunction has been linked to developmental disorders and cancer. DNMT3A is frequently mutated in myeloid malignancies with the majority of mutations occurring at Arg-882, where R882H mutations are most frequent. The R882H mutation causes a reduction in DNA methyltransferase activity and hypomethylation at differentially-methylated regions within the genome, ultimately preventing hematopoietic stem cell differentiation and leading to leukemo-genesis. Although the means by which the R882H DNMT3A mutation reduces enzymatic activity has been the subject of several studies, the precise mechanism by which this occurs has been elusive. Herein, we demonstrate that in the context of the full-length DNMT3A protein, the R882H mutation stabilizes the formation of large oligomeric DNMT3A species to reduce the overall DNA methyltransferase activity of the mutant protein as well as the WT-R882H complex in a dominant-negative manner. This shift in the DNMT3A oligomeric equilibrium and the resulting reduced enzymatic activity can be partially rescued in the presence of oligomer-disrupting DNMT3L, as well as DNMT3A point mutations along the oligomer-forming interface of the catalytic domain. In addition to modulating the oligomeric state of DNMT3A, the R882H mutation also leads to a DNA-binding defect, which may further reduce enzymatic activity. These findings provide a mechanistic explanation for the observed loss of DNMT3A activity associated with the R882H hot spot mutation in cancer. [ABSTRACT FROM AUTHOR]

Published
2019
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