Leena Hilakivi Clarke

Professor
[email protected]

80116th Ave NE
Austin, MN 55912
United States

Hormel Institute faculty profile
Education

Obtained PhD in Experimental Psychology and Physiology from the University of Helsinki, Finland in 1987.

Fogarty post-doctoral Fellow at the National Institutes of Health in Bethesda, MD in 1987-1990

Faculty (from research Associate Professor to tenured full Professor) at Georgetown University, Washington DC in 1991-2020

Areas of Interest

  • Breast Cancer
  • Nutrition, including Maternal Nutrition
  • Obesity
  • Cancer Prevention
  • Epigenetics
  • Inflammation
  • Cancer Immune Microenvironment
  • Gut Microbiota
  • Stress and Cancer

Biography

Dr. Leena Hilakivi-Clarke’s research involves studying the role of dietary factors in affecting breast cancer risk and mortality. She investigates how maternal diet and obesity during pregnancy can pre-program offspring’s risk of developing breast cancer, focusing on persistent changes in the offspring’s epigenome, gut microbiota and inflammatory pathways. She also studies possible interventions that could be implemented either during pregnancy or to adult offspring to prevent their increased breast cancer risk and risk of breast cancer recurrence.  These interventions include bioactive compounds in foods, such as genistein and vitamin D, beneficial dietary fats, or traditional anti-inflammatory herb mixtures. Another research topic Dr. Hilakivi-Clarke has been studying is the biological changes caused by social isolation and loneliness that could explain why socially isolated individuals are at a significantly increased risk of dying of breast cancer. Along with smoking and obesity, social isolation is linked to adverse health outcomes. Dr. Hilakivi-Clarke collaborates closely with experts in computational modeling and has several past collaborations with epidemiologists to translate her preclinical findings to the clinic.

Select Publications

Maternal or paternal dietary and hormonal exposures during pregnancy and breast cancer risk among offspring

  1. Hilakivi-Clarke LA, Clarke R, Onojafe I, Raygada M, Cho E, Lippman ME. A maternal diet high in n-6 polyunsaturated fats alters mammary gland development, puberty onset, and breast cancer risk among female rat offspring. PNAS 94:93729377, 1997. PMID: 9256489
  2. de Assis S, Warri A, Olufunto S, Cruz I, Wang Y, Tian Y, Zhang B, Huang T, Hilakivi-Clarke LA. High-fat or ethinyloestradiol intake during pregnancy increases mammary cancer risk in several generations of female offspring. Nature Communications 3:1053-, 2012. PMID: 22968699
  3. Hilakivi-Clarke L, Warri A, Bouker KB, Zhang X, Cook KL, Jin L, Zwart A, Nguyen N, Hu R, Cruz MI, de Assis S, Wang X, Xuan J, Wang Y, Wehrenberg B, and Clarke R. Effects of in utero exposure to ethinyl estradiol on tamoxifen resistance and breast cancer recurrence in a preclinical model. JNCI 2016:109. PMID: 27609189
  4. Zhang X, de Oliveira Andrade F, Zhang H, Cruz I, Clarke R, Gaur P, Verma V, Hilakivi-Clarke L. Maternal obesity increases offspring’s mammary cancer recurrence and impairs tumor immune response. Endocrine Relat Cancer 27:1-14, 2020. PMID: 32580156

Maternal dietary and hormonal exposures during pregnancy and mother’s breast cancer risk

  1. Hilakivi-Clarke LA, Cho E, Raygada M, Onojafe I, Clarke R, Lippman ME. Breast cancer risk in rats fed a diet high in n-6 polyunsaturated fatty acids during pregnancy. JNCI, 88:1821-1827, 1996. PMID: 8961971
  2. Hilakivi-Clarke LA, Luoto R, Huttunen T, Koskenvuo M. Body mass index, pregnancy weight gain and premenopausal breast cancer risk. J Reproductive Med 50:811-6, 2005. PMID: 16419626 L
  3. uoto R, Kharazmi E, Saarinen NM, Smeds AI, Mäkelä S, Fallah M, Raitanen J, Hilakivi-Clarke LA. Effect of dietary intervention on serum lignan levels in pregnant women. Reprod Health. Oct 8;7:26, 2010. PMID: 20932282
  4. de Assis S, Wang M, Jin L, Bouker KB, Hilakivi-Clarke LA. Exposure to excess estradiol or leptin during pregnancy increases mammary cancer risk and prevents parity-induced protective genomic changes in rats. Cancer Prev Res (Phila). 2013 Nov;6(11):1194-211. PMID: 24169961

Genistein intake, intake of herb mixures and breast cancer

  1. Trock BJ, Hilakivi-Clarke LA, Clarke R. Meta-Analysis of Soy Intake and Breast Cancer Risk. JNCI 98(7):459-71, 2006. PMID: 16595782 de Assis S, Warri A, Benitez C, Helferich W, Hilakivi-Clarke LA. Protective effects of prepubertal genistein exposure on mammary tumorigenesis are dependent on BRCA1 expression. Cancer Prevention Research 4:1436-48, 2011. PMID: 21680703
  2. Zhang X, Cook KL, Warri A, Cruz MI, Rosim M, Riskin J, Helferich W, Doerge D, Clarke R and Hilakivi-Clarke L. Lifetime genistein intake increases the response of mammary tumors to tamoxifen in rats. Clin Cancer Res 23:814-824, 2017. PMID: 28148690
  3. De Oliveira Andrade F, Wei Y, Zhang X, Carney E, Hu R, Clarke R, FitzGerald K, Hilakivi-Clarke L. Effects of Jaeumkanghwa-tang on tamoxifen responsiveness in preclinical ER+ breast cancer model. Endocr Relat Cancer. 26: 339– 353, 2019. PMID: 30640711

Stress and cancer risk

  1. Hilakivi LA, Lister RG, Durcan MJ, Ota M, Mefford I, Eskey R, Linnoila M. Behavioral, hormonal and neurochemical characteristics of aggressive alpha mice. Brain Res 502, 158-166, 1989. PMID: 2819452
  2. Hilakivi-Clarke LA, Rowland J, Clarke R, Lippman ME. Psychosocial factors in the development and progression of breast cancer. Breast Cancer Res. Treat. 29:141-160, 1993. PMID: 8012033
  3. Cabanes A, de Assis S, Gustafsson J-A, Hilakivi-Clarke L. Maternal high-fat intake during pregnancy increases voluntary alcohol intake and hypothalamic estrogen receptor protein levels among female offspring. Dev Neuroscience 22:488-93, 2000. PMID: 11111167
  4. Sumis A, Cook KL, Andrade F, Bouker KB, Xiyuan Z, Hu R, Kidney E, Kim D, Carney E, Nguyen N, Yu W, Cruz I, Clarke R Hilakivi-Clarke LA. Social isolation induces unfolded protein response and autophagy in the mouse mammary gland: link to obesity and mammary cancer risk. Endocrine Related Cancer 23(10):839-56, 2016 PMID: 27550962. This paper won 2017 Society for Endocrinology’s Journal Award.