Page 23 - Hormel Report 2023

sensors of, and responders to energy changes induced by endocrine therapies in endocrine sensitive and resistant ER+ breast cancer cells. To achieve the goals of this project we will first measure expression of SIRTS 1-7 in different
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.
ORCID iD: https://orcid.org/0000-0002-9278-0854
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PUBLICATION HIGHLIGHT:
• Chen, L. L., Wu, C. T., Lin, C. H., Dai, R. J., Liu, C. Y., Clarke, R., Yu, G. Q., Van Eyk, J. E., Herrington, D. M., & Wang, Y. (2022). swCAM: estimation of subtype- specific expressions in individual samples with unsupervised sample-wise deconvolution. Bioinformatics, 38(5), 1403-1410.
• Andrade, F. D. O., Jin, L., Clarke, R., Wood, I., Dutton, M., Anjorin, C., Rubin,
G., Gao, A., Sengupta, S., FitzGerald, K., & Hilakivi-Clarke, L. (2023). Social Isolation Activates Dormant Mammary Tumors, and Modifies Inflammatory and Mitochondrial Metabolic Pathways in the Rat Mammary Gland. Cells, 12(6), 961.
• de Oliveira, K. A., Sengupta, S., Yadav, A. K., & Clarke, R. (2023). The complex nature of heterogeneity and its roles in breast cancer biology and therapeutic responsiveness. Frontiers in Endocrinology, 14, 1083048.
• Srinivasan, M., Clarke, R., & Kraikivski, P. (2022). Mathematical Models of Death Signaling Networks. Entropy, 24(10), 22.
• 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. Bioinformatics Advances, 2(1), vbac037.
• Clarke, R. (2023). Introduction: Cancer Systems and Integrative Biology. Methods Mol Biol, 2660, 1-11.