Research Assistant Professor, Chemistry and Biochemistry
University of Notre Dame
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.
The histological analysis of human ovarian tumor tissues including rare granulosa cell tumors are also of interest. Histological analysis of granulosa cell tumors divided into cohorts according to body mass index (BMI) [low BMI (<30) and high BMI (>30)] will advance our understanding of the influence of host factors including obesity on rare cases of ovarian cancer metastasis. Of interest are expression levels of obesity related genes, and genes involved in proliferation and migration between the cohorts.
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.
- Hilliard, T.S. "The impact of Mesothelin in the Ovarian cancer tumor microenvironment" 2018 Cancers, 10 (9), 277. DOI: 10.3390/cancers10090277
- Loughran, E.A., Leonard, A.K., Hilliard, T.S., Phan, R.C., Yemc, M.G., Harper, E., Sheedy, E., Klymenko, Y., Asem, M., Liu, Y., Yang, J., Johnson, J., Tarwater, L., Shi, Z., Leevy, M., Ravosa, M.J., Stack, M.S. "Aging Increases Susceptibility to Ovarian Cancer Metastasis in Murine Allograft Models and Alters Immune Composition of Peritoneal Adipose Tissue" 2018 Neoplasia (United States), 20 (6), pp. 621-631. DOI: 10.1016/j.neo.2018.03.007
- Loughran, E.A., Phan, R.C., Leonard, A.K., Tarwater, L., Asem, M., Liu, Y., Yang, J., Klymenko, Y., Johnson, J., Shi, Z., Hilliard, T.S., Blumenthaler, M., Leevy, M., Ravosa, M.J., Stack, M.S. "Multiparity activates interferon pathways in peritoneal adipose tissue and decreases susceptibility to ovarian cancer metastasis in a murine allograft model" 2017 Cancer Letters, 411, pp. 74-81. DOI: 10.1016/j.canlet.2017.09.028
- Hilliard, T.S., Miklossy, G., Chock, C., Yue, P., Williams, P., Turkson, J. "15α-methoxypuupehenol induces antitumor effects in vitro and in vivo against human glioblastoma and breast cancer models" 2017 Molecular Cancer Therapeutics, 16 (4), pp. 601-613. DOI: 10.1158/1535-7163.MCT-16-0291
- Yue, P., Lopez-Tapia, F., Paladino, D., Li, Y., Chen, C.-H., Namanja, A.T., Hilliard, T., Chen, Y., Tius, M.A., Turkson, J. "Hydroxamic acid and benzoic acid-based STAT3 inhibitors suppress human glioma and breast cancer phenotypes in vitro and in vivo" 2016 Cancer Research, 76 (3), pp. 652-663. DOI: 10.1158/0008-5472.CAN-14-3558
- Miklossy, G., Youn, U.J., Yue, P., Zhang, M., Chen, C.-H., Hilliard, T.S., Paladino, D., Li, Y., Choi, J., Sarkaria, J.N., Kawakami, J.K., Wongwiwatthananukit, S., Chen, Y., Sun, D., Chang, L.C., Turkson, J. "Hirsutinolide Series Inhibit Stat3 Activity, Alter GCN1, MAP1B, Hsp105, G6PD, Vimentin, TrxR1, and Importin α-2 Expression, and Induce Antitumor Effects against Human Glioma" 2015 Journal of Medicinal Chemistry, 58 (19), pp. 7734-7748. DOI: 10.1021/acs.jmedchem.5b00686