Page 23 - Hormel Institute Annual Report 2021-22

cell lines under different treatment conditions and determined that high expression of SIRT3 may promote endocrine therapy resistance by altering mitochondrial functions. Further, we will identify other members of SIRT signaling module by using gene network modeling tools in our cell lines and patient transcriptome data sets.
Role of de-novo purine synthesis in endocrine therapy resistance: The aim
of this project is to study the critical
role of adenylosuccinate lyase (ADSL) enzyme, which is involved in de-novo synthesis of GMP and AMP, in endocrine therapy resistant breast cancer cells. We have observed that siRNA mediated depletion of ADSL in ER+, endocrine
therapy resistant breast cancer cells lead to severe inhibition of growth. To further determine the mechanism, we will investigate the involvement of cell cycle machinery and mitochondrial function in ADSL depleted cells and if it can be rescued by the products (metabolites) of ADSL enzymatic reaction.
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Recent Publications:
• Jones, B. C., Pohlmann, P. R., Clarke, R., & Sengupta, S. (2022). Treatment against glucose-dependent cancers through metabolic PFKFB3 targeting of glycolytic flux. Cancer Metastasis Rev, 41(2), 447-458.
• Lu, Y., Wu, C. T., Parker, S. J., Cheng, Z., Saylor, G., Van Eyk, J. E., Yu, G., Clarke, R., Herrington, D. M., & Wang, Y. (2022). COT: an efficient and accurate method for detecting marker genes among many subtypes. Bioinform Adv, 2(1), vbac037.
• Clarke, R., Jones, B. C., Sevigny, C. M., Hilakivi-Clarke, L. A., & Sengupta, S. (2021). Experimental models of endocrine responsive breast cancer: strengths, limitations, and use. Cancer Drug Resist, 4(4), 762-783.
• Shi, X., Wang, X., Neuwald, A. F., Halakivi-Clarke, L., Clarke, R., & Xuan, J. (2021). A Bayesian approach for accurate de novo transcriptome assembly. Sci Rep, 11(1), 17663.
• Chen, X., Neuwald, A. F., Hilakivi-Clarke, L., Clarke, R., & Xuan, J. (2021). ChIP-GSM: Inferring active transcription factor modules to predict functional regulatory elements. PLoS Comput Biol, 17(7), e1009203.
• Chen, X., Gu, J., Neuwald, A. F., Hilakivi-Clarke, L., Clarke, R., & Xuan, J. (2021). Identifying intracellular signaling modules and exploring pathways associated with breast cancer recurrence. Sci Rep, 11(1), 385.
• Chen, L., Lu, Y., Wu, C. T., Clarke, R., Yu, G., Van Eyk, J. E., Herrington, D. M., & Wang, Y. (2021). Data-driven detection of subtype-specific differentially expressed genes. Sci Rep, 11(1), 332.
• Perrotti, E., Acchioni, M., Orsatti, R., Acchioni, C., Battistini, A., Clarke, R., & Marsili, G. (2020). IκB kinase-ε-mediated phosphorylation triggers IRF-1 degradation in breast cancer cells. Neoplasia, 22(10), 459-469.
• Fan, M., Xia, P., Clarke, R., Wang, Y., & Li, L. (2020). Radiogenomic signatures reveal multiscale intratumour heterogeneity associated with biological functions and survival in breast cancer. Nat Commun, 11(1), 4861.
ORCID iD: https://orcid.org/0000-0002-9278-0854