Page 32 - Hormel Report 2023

Leena Hilakivi-Clarke, PhD
“Minnesota has the third highest incidence of breast cancer in the United States. The causes of breast cancer remain largely unknown. Nutrition, obesity and other lifestyle factors, such as social stress, and exposures to aromatic compounds from vehicle emission, especially when exposed already in the womb through a pregnant mother, have a profound impact on breast cancer risk
and response to breast cancer therapies.”
Leena Hilakivi-Clarke
32 | THE HORMEL INSTITUTE Women’s Health
ASSISTANT DIRECTOR FOR FACULTY AFFAIRS / PROFESSOR
// UNIVERSITY OF MINNESOTA
Maternal Obesity and Increased Breast Cancer Risk and Mortality among Female Offspring.
We are performing preclinical studies to identify targetable mechanisms that increase breast can- cer risk and mortality in daughters born to over- weight or obese mothers, or daughters exposed to BTEX chemicals in utero. The mechanisms studied center on the gut microbiome and its effect on epigenome and immune cells. We also study if the adverse effects of obesity or BTEX exposure during pregnancy on offspring can be prevented by feeding pregnant dams or offspring dietary fiber that reverses gut dysbiosis. These studies are funded by RO1 from the National Can- cer Institute and Absolute Energy, LLC.
Social Isolation and Breast Cancer.
Social isolation increases early mortality, including by increasing breast cancer risk and recurrence. We are studying if gut dysbiosis caused by social isolation is induced by the sympathetic nervous system, especially activation of β-adrenergic
receptors, and whether gut dys- biosis then mediates impaired tumor immune responses and increased mammary tumorigen- esis already observed in mouse models. Like in the maternal obesity study, we are deter- mining if the adverse effects of social isolation can be reversed by consumption of dietary fiber as well as β-adrenergic receptor blockers. Funding for the study has been obtained from Paint the Town Pink.
Combined Effects of Hormone Therapy and 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 plant-derived genistein, will improve response to anti-PD1 therapy in ER neg- ative (ER-) and/or ER+ breast cancer in preclinical models. We are also studying if these effects are mediated through the gut microbiota. This study was funded by an R21 grant from the National Institutes of Health.
Potential Health Benefits of Organic Beef.
Little is known about the potential human health benefits of beef from organically fed cattle. We are investigating whether organic beef that contains plant-derived phytochemicals will improve gut microbiota composition in prediabetic individuals and might prevent them from progressing to type 2 diabetes. This human dietary intervention study is scheduled to start recruiting participants during Fall 2023. The study is funded by Applegate.
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 designing clinical intervention studies to deter- mine the effects of walnuts on cardiac function in breast cancer patients on aromatase inhibitor therapy. This study was funded by the Windfeldt Research Award.