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8 results on '"Khan, Showkhin"'

1. Discovery of a highly potent, selective, orally bioavailable inhibitor of KAT6A/B histone acetyltransferases with efficacy against KAT6A-high ER+ breast cancer

Author

Sharma, Shikhar, Chung, Chi-Yeh, Uryu, Sean, Petrovic, Jelena, Cao, Joan, Rickard, Amanda, Nady, Nataliya, Greasley, Samantha, Johnson, Eric, Brodsky, Oleg, Khan, Showkhin, Wang, Hui, Wang, Zhenxiong, Zhang, Yong, Tsaparikos, Konstantinos, Chen, Lei, Mazurek, Anthony, Lapek, John, Kung, Pei-Pei, Sutton, Scott, Richardson, Paul F., Greenwald, Eric C., Yamazaki, Shinji, Jones, Rhys, Maegley, Karen A., Bingham, Patrick, Lam, Hieu, Stupple, Alexandra E., Kamal, Aileen, Chueh, Anderly, Cuzzupe, Anthony, Morrow, Benjamin J., Ren, Bin, Carrasco-Pozo, Catalina, Tan, Chin Wee, Bhuva, Dharmesh D., Allan, Elizabeth, Surgenor, Elliot, Vaillant, François, Pehlivanoglu, Havva, Falk, Hendrik, Whittle, James R., Newman, Janet, Cursons, Joseph, Doherty, Judy P., White, Karen L., MacPherson, Laura, Devlin, Mark, Dennis, Matthew L., Hattarki, Meghan K., De Silva, Melanie, Camerino, Michelle A., Butler, Miriam S., Dolezal, Olan, Pilling, Patricia, Foitzik, Richard, Stupple, Paul A., Lagiakos, H. Rachel, Walker, Scott R., Hediyeh-Zadeh, Soroor, Nuttall, Stewart, Spall, Sukhdeep K., Charman, Susan A., Connor, Theresa, Peat, Thomas S., Avery, Vicky M., Bozikis, Ylva E., Yang, Yuqing, Zhang, Ming, Monahan, Brendon J., Voss, Anne K., Thomas, Tim, Street, Ian P., Dawson, Sarah-Jane, Dawson, Mark A., Lindeman, Geoffrey J., Davis, Melissa J., Visvader, Jane E., and Paul, Thomas A.

Published
2023
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3. Asparagine bioavailability governs metastasis in a model of breast cancer

Author

Knott, Simon RV, Wagenblast, Elvin, Khan, Showkhin, Kim, Sun Y, Soto, Mar, Wagner, Michel, Turgeon, Marc-Olivier, Fish, Lisa, Erard, Nicolas, Gable, Annika L, Maceli, Ashley R, Dickopf, Steffen, Papachristou, Evangelia K, D’Santos, Clive S, Carey, Lisa A, Wilkinson, John E, Harrell, J Chuck, Perou, Charles M, Goodarzi, Hani, Poulogiannis, George, and Hannon, Gregory J

Subjects
Ecological Applications, Biomedical and Clinical Sciences, Environmental Sciences, Oncology and Carcinogenesis, Breast Cancer, Cancer, Animals, Asparaginase, Asparagine, Aspartate-Ammonia Ligase, Biological Availability, Breast Neoplasms, Cell Line, Tumor, Disease Models, Animal, Disease Progression, Epithelial-Mesenchymal Transition, Female, Humans, Lung Neoplasms, Male, Mice, Neoplasm Invasiveness, Neoplasm Metastasis, Prognosis, Prostatic Neoplasms, RNA Interference, Reproducibility of Results, General Science & Technology
Abstract

Using a functional model of breast cancer heterogeneity, we previously showed that clonal sub-populations proficient at generating circulating tumour cells were not all equally capable of forming metastases at secondary sites. A combination of differential expression and focused in vitro and in vivo RNA interference screens revealed candidate drivers of metastasis that discriminated metastatic clones. Among these, asparagine synthetase expression in a patient's primary tumour was most strongly correlated with later metastatic relapse. Here we show that asparagine bioavailability strongly influences metastatic potential. Limiting asparagine by knockdown of asparagine synthetase, treatment with l-asparaginase, or dietary asparagine restriction reduces metastasis without affecting growth of the primary tumour, whereas increased dietary asparagine or enforced asparagine synthetase expression promotes metastatic progression. Altering asparagine availability in vitro strongly influences invasive potential, which is correlated with an effect on proteins that promote the epithelial-to-mesenchymal transition. This provides at least one potential mechanism for how the bioavailability of a single amino acid could regulate metastatic progression.

Published
2018

5. Abstract 1130: First-in-class KAT6A/KAT6B inhibitor CTx-648 (PF-9363) demonstrates potent anti-tumor activity in ER+ breast cancer with KAT6A dysregulation

Author

Sharma, Shikhar, primary, Chung, Jay, additional, Uryu, Sean, additional, Rickard, Amanda, additional, Nady, Natalie, additional, Khan, Showkhin, additional, Wang, Zhenxiong, additional, Zhang, Yong, additional, Zhang, Haikuo, additional, Kung, Pei-Pei, additional, Greenwald, Eric, additional, Maegley, Karen, additional, Bingham, Patrick, additional, Lam, Hieu, additional, Bozikis, Ylva E., additional, Falk, Hendrik, additional, Allan, Elizabeth, additional, Avery, Vicky M., additional, Butler, Miriam S., additional, Camerino, Michelle A., additional, Carrasco-Pozo, Catalina, additional, Charman, Susan A., additional, Davis, Melissa J., additional, Dawson, Mark A., additional, Sarah-Jane, Dawson, additional, de Silva, Melanie, additional, Dennis, Matthew L., additional, Dolezal, Olan, additional, Lagiakos, Rachel, additional, Lindeman, Geoffrey J., additional, MacPherson, Laura, additional, Nuttall, Stewart, additional, Peat, Thomas S., additional, Ren, Bin, additional, Stupple, Alexandra E., additional, Surgenor, Elliot, additional, Tan, Chin Wee, additional, Thomas, Tim, additional, Visvader, Jane E., additional, Voss, Anne K., additional, Vaillant, Francois, additional, White, Karen L., additional, Whittle, James, additional, Yang, Yuqing, additional, Hediyeh-Zadeh, Soroor, additional, Stupple, Paul A., additional, Street, Ian P., additional, Monahan, Brendon J., additional, and Paul, Thomas, additional

Published
2021
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6. Asparagine bioavailability governs metastasis in a model of breast cancer.

Author

Knott, Simon, Knott, Simon, Wagenblast, Elvin, Khan, Showkhin, Kim, Sun, Soto, Mar, Wagner, Michel, Turgeon, Marc-Olivier, Fish, Lisa, Erard, Nicolas, Gable, Annika, Maceli, Ashley, Dickopf, Steffen, Papachristou, Evangelia, DSantos, Clive, Carey, Lisa, Wilkinson, John, Harrell, J, Perou, Charles, Poulogiannis, George, Hannon, Gregory, Goodarzi, Hani, Knott, Simon, Knott, Simon, Wagenblast, Elvin, Khan, Showkhin, Kim, Sun, Soto, Mar, Wagner, Michel, Turgeon, Marc-Olivier, Fish, Lisa, Erard, Nicolas, Gable, Annika, Maceli, Ashley, Dickopf, Steffen, Papachristou, Evangelia, DSantos, Clive, Carey, Lisa, Wilkinson, John, Harrell, J, Perou, Charles, Poulogiannis, George, Hannon, Gregory, and Goodarzi, Hani

Abstract

Using a functional model of breast cancer heterogeneity, we previously showed that clonal sub-populations proficient at generating circulating tumour cells were not all equally capable of forming metastases at secondary sites. A combination of differential expression and focused in vitro and in vivo RNA interference screens revealed candidate drivers of metastasis that discriminated metastatic clones. Among these, asparagine synthetase expression in a patients primary tumour was most strongly correlated with later metastatic relapse. Here we show that asparagine bioavailability strongly influences metastatic potential. Limiting asparagine by knockdown of asparagine synthetase, treatment with l-asparaginase, or dietary asparagine restriction reduces metastasis without affecting growth of the primary tumour, whereas increased dietary asparagine or enforced asparagine synthetase expression promotes metastatic progression. Altering asparagine availability in vitro strongly influences invasive potential, which is correlated with an effect on proteins that promote the epithelial-to-mesenchymal transition. This provides at least one potential mechanism for how the bioavailability of a single amino acid could regulate metastatic progression.

Published
2018

7. Erratum: Asparagine bioavailability governs metastasis in a model of breast cancer

Author

Knott, Simon R. V., Wagenblast, Elvin, Khan, Showkhin, Kim, Sun Y., Soto, Mar, Wagner, Michel, Turgeon, Marc-Olivier, Fish, Lisa, Erard, Nicolas, Gable, Annika L., Maceli, Ashley R., Dickopf, Steffen, Papachristou, Evangelia K., DSantos, Clive S., Carey, Lisa A., Wilkinson, John E., Harrell, J. Chuck, Perou, Charles M., Goodarzi, Hani, Poulogiannis, George, and Hannon, Gregory J.

Subjects
High performance liquid chromatography, Asparagine, Breast cancer, Cancer metastasis, Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

Author(s): Simon R. V. Knott; Elvin Wagenblast; Showkhin Khan; Sun Y. Kim; Mar Soto; Michel Wagner; Marc-Olivier Turgeon; Lisa Fish; Nicolas Erard; Annika L. Gable; Ashley R. Maceli; Steffen Dickopf; [...]

Published
2018
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8. Using Cultured Mammalian Neurons to Study Cellular Processes and Neurodegeneration: A Suite of Undergraduate Lab Exercises.

Author

Catlin R, Taylor A, Ditchek L, Burnett S, Khan S, Todd O, Adams M, Touhey E, Wynkoop A, and Ryan J

Abstract

Cell culture is a powerful tool for exploring cellular function. Culturing primary neurons has revealed how neurons communicate in learning and memory (Kandel, 2006) and provided insights into the mechanisms of neurodegenerative diseases such as Parkinson's and Alzheimer's disease (Alberio et al., 2012; Trinchese, et al., 2004). Here we describe a series of four modular laboratory exercises to integrate this neuroscience technique in undergraduate teaching laboratories. First, we describe the modular approach. Then we provide educators with simple techniques for culturing rat primary neurons, performing immunohistochemistry to label cellular components, and illustrating neurodegeneration caused by reactive oxygen species. We describe teaching exercises that culminate in student-generated research projects. Finally, we describe potential barriers students may face when integrating modern cell culture experiments into teaching laboratories.

Published
2016

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