Page 33 - Hormel Institute Annual Report 2021-22

Combined effects of anti-estrogens and gut microbiota modification with plant-derived compounds on anti-PD1 therapy response. We are studying if inhibiting estrogen receptor (ER)α in immune cells with fulvestrant along with activation of G-protein coupled estrogen receptor (GPER) and ERβ with genistein, will improve response to anti-PD1 therapy in ER negative (ER-) breast cancer in a preclinical model. We are also studying if these effects are mediated through the gut microbiota.
Alpha-linolenic acid in preventing cardiovascular damage caused by aromatase inhibitors. In collaboration with
Dr. Luke Hoeppner’s laboratory, we are determining if alpha-linolenic acids in walnuts will block the adverse effects of aromatase inhibitors on cardiovascular dysfunction in a zebrafish model. We also are design- ing clinical intervention studies to determine the effects of walnuts on cardiac function in breast cancer patients on aromatase inhibitor therapy.
Mechanisms of assembly of higher order structures: Social isolation increases tumor recurrence and tumor burden after tamoxifen (TAM) therapy and increase inflammation and impairs oxidative phosphorylation in preclinical model. A) Social isolation (SI) increases tumor recurrence after TAM therapy ends compared to group-housed (GH). B) SI increases tumor burden compared to GH after TAM therapy. C) SI increases inflammatory pathways (IL6-JAK-STAT3) and impairs oxidative phosphor- ylation. D) Social increases percentage and activation of immunosuppressive cells MDSCs.
Effects of genistein on response of anti-PD1 therapy combined with tamox- ifen in estrogen receptor negative (ER-) preclinical model.
A) Tumor burden during tamoxifen (TAM), anti-PD1 or isotype control (IGG) treatment with control diet or diet with high levels of genistein. B) List of pathways activated and suppressed by combination of tamoxifen and
anti-PD1 treatment with high levels of genistein diet.
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Recent Publications:
• Andrade, F. O., Liu, F., Zhang, X., Rosim, M. P., Dani, C., Cruz, I., Wang, T. T. Y., Helferich, W., Li, R. W., & Hilakivi-Clarke, L. (2021). Genistein Reduces the Risk of Local Mammary Cancer Recurrence and Ameliorates Alterations in the Gut Microbiota in the Offspring of Obese Dams. Nutrients, 13(1), 201.
• Li, Y., Cook, K. L., Yu, W., Jin, L., Bouker, K. B., Clarke, R., & Hilakivi-Clarke,
L. (2021). Inhibition of Antiestrogen-Promoted Pro-Survival Autophagy and Tamoxifen Resistance in Breast Cancer through Vitamin D Receptor. Nutrients, 13(5), 1715.
• 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.
• 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.
ORCID iD: https://orcid.org/0000-0002-7052-6513