Tyvette Hilliard

Research Interests

The overall objective of my research is to determine the influence of host factors, including obesity, on the metastatic success of ovarian cancer (OvCa). OvCa is the deadliest gynecological cancer among U.S. women due to women presenting with advanced stage disease, with widely disseminated intraperitoneal metastasis, at diagnosis. My main project focuses on investigating the influence of maternal obesity on the metastatic success of OvCa in next generation offspring. Obesity has become a worldwide epidemic with increased prevalence in children. Maternal obesity often results in an increased risk of offspring developing obesity and obesity-linked diseases. The excessive intake of nutrients may cause epigenetic changes, consequently changing the expression of critical genes associated with physiological and pathological processes. Using established pre-clinical mouse models of diet-induced obesity and intraperitoneal metastasis, an integrated approach encompassing a variety of epigenetic, genetic, biophysical and micro-anatomical methods is used to investigate the mechanistic link between maternal obesity and OvCa metastasis in offspring.

Another project involves the histological analysis of human ovarian tumor tissues including granulosa cell tumors. The tumor tissues will be divided into cohorts according to body mass index (BMI) [low BMI (<30) and high BMI (>30)] to compare expression levels of obesity related genes and genes involved in proliferation and migration between the cohorts. The expected results will advance our understanding of the influence of host factors including obesity on ovarian cancer metastasis. An additional project uses an OvCa intraperitoneal metastasis model utilizing mesothelin wild type and knockout mice to explore the role of mesothelin expression, a glycoprotein overexpressed in OvCa, on the susceptibility of OvCa cells to adhere to the mesothelium of organs in the peritoneal cavity.

Selected Publications

• Liu, Y. Y.; Yang, J.; Hilliard, T. S.; Wang, Z. K.; Johnson, J.; Wang, W. R.; Harper, E. I.; Ott, C.; O'Brien, C.; Campbell, L.; Crowley, B.; Grisoli, S.; Stavrou, N. M.; Juncker-Jensen, A. and Stack, M. S. "Host Obesity Alters the Ovarian Tumor Immune Microenvironment and Impacts Response to Standard of Care Chemotherapy" 2023 Journal of Experimental & Clinical Cancer Research, 42 (1), 165. DOI: 10.1186/s13046-023-02740-y.
• Harper, E. I.; Siroky, M. D.; Hilliard, T. S.; Dominique, G. M.; Hammond, C.; Liu, Y. Y.; Yang, J.; Hubble, V. B.; Walsh, D. J.; Melander, R. J.; Melander, C.; Ravosa, M. J. and Stack, M. S. "Advanced Glycation End Products as a Potential Target for Restructuring the Ovarian Cancer Microenvironment: A Pilot Study" 2023 International Journal of Molecular Sciences, 24 (12), 9804. DOI: 10.3390/ijms24129804.
• Amens, J. N.; Bahcecioglu, G.; Dwyer, K.; Yue, X. S.; Stack, M. S.; Hilliard, T. S. and Zorlutuna, P. "Maternal Obesity Driven Changes in Collagen Linearity of Breast Extracellular Matrix Induces Invasive Mammary Epithelial Cell Phenotype" 2023 Biomaterials, 297, 122110. DOI: 10.1016/j.biomaterials.2023.122110.
• Hilliard, T. S.; Kowalski, B.; Iwamoto, K.; Agadi, E. A.; Liu, Y. Y.; Yang, J.; Asem, M.; Klymenko, Y.; Johnson, J.; Shi, Z. G.; Marfowaa, G.; Yemc, M. G.; Petrasko, P. and Stack, M. S. "Host Mesothelin Expression Increases Ovarian Cancer Metastasis in the Peritoneal Microenvironment" 2021 International Journal of Molecular Sciences, 22 (22), 12443. DOI: 10.3390/ijms222212443.
• Liu, Y. Y.; Yang, J.; Shi, Z. G.; Tan, X. J.; Jin, N.; O'Brien, C.; Ott, C.; Grisoli, A.; Lee, E.; Volk, K.; Conroy, M.; Franz, E.; Bryant, A.; Campbell, L.; Crowley, B.; Grisoli, S.; Alexandrou, A. T.; Li, C. Y.; Harper, E. I.; Asem, M.; Johnson, J.; Leonard, A.; Santanello, K.; Klein, A.; Wang, Q. F.; Zhang, S. Y.; Hilliard, T. S. and Stack, M. S. "In Vivo Selection of Highly Metastatic Human Ovarian Cancer Sublines Reveals Role for AMIGO2 in Intra-Peritoneal Metastatic Regulation" 2021 Cancer Letters, 503, pp.163-173. DOI: 10.1016/j.canlet.2021.01.024.
• Asem, M.; Young, A. M.; Oyama, C.; Claure de la Zerda, A.; Liu, Y. Y.; Yang, J.; Hilliard, T. S.; Johnson, J.; Harper, E. I.; Guldner, I.; Zhang, S. Y.; Page-Mayberry, T.; Kaliney, W. J. and Stack, M. S. "Host Wnt5a Potentiates Microenvironmental Regulation of Ovarian Cancer Metastasis" 2020 Cancer Research, 80 (5), pp.1156-1170. DOI: 10.1158/0008-5472.CAN-19-1601.