Kleiderer-Pezold Professor of Biochemistry; Ann F. Dunne & Elizabeth Riley Director, Harper Cancer Research Institute
- A200D Harper Hall
Notre Dame, IN 46556
- +1 574-631-2518
- Life Processes
Prospective Graduate Students
|2011-present||Professor and Director, Harper Cancer Research Institute, University of Notre Dame|
|2007-2011||Professor and Vice-Chair for Research,University of Missouri School of Medicine|
|2006-2007||Professor, Northwestern University Medical School|
|2000-2006||Associate Professor, Northwestern University Medical School|
|1994-2000||Assistant Professor, Northwestern University Medical School|
|1991-1994||Assistant Research Professor, Duke University Medical Center|
|1989-1991||Postdoctoral Research Associate, Duke University Medical Center|
|1989||Ph.D. in Biochemistry, University of Louisville|
|1985||M.S. in Biomedical Sciences/Biochemistry, East Tennessee State University|
|1981||B.S. in Biochemistry, Clemson University|
2015 Juan Garcia Lifetime Achievement Award, American Cancer Society Lakeshore Division
2014 Herbert Fanger Lecture Honoree, Brown University
2014 Provost's Faculty Recognition Award
2012 Fellow, American Association for the Advancement of Science
My laboratory has focused for many years on regulation of metastasis, with specific emphasis on the role of cell adhesion and matrix remodeling in two tumor models: epithelial ovarian cancer (OvCa) and squamous cell carcinoma of the oral cavity (OSCC). Metastatic OvCa cells colonize the peritoneal cavity following dissemination from the ovarian surface, survival in suspension as multicellular aggregates (MCAs) in carcinomatous ascites fluid, attachment to the peritoneal surface, and localized invasion into the sub-mesothelial matrix to anchor secondary lesions. We have developed a number of in vitro 3-dimensional and organotypic models of key events in OvCa metastasis with which to evaluate the effect of various cellular and micro-environmental manipulations on metastatic success with an overarching focus on adhesion (cell-matrix and cell-cell) and matrix proteolysis (pericellular and extracellular remodeling). We have used organotypic mesothelial-mimetic (meso-mimetic) cultures comprised of fibroblast-embedded 3D collagen gels overlaid with mesothelial cells as well as ex vivo tissue explant models of the peritoneum and omentum. Additionally, we have focused extensively on xenograft and allograft studies of OvCa intra-peritoneal metastasis, with particular emphasis on the use of advanced imaging methods to accurately quantify widely disseminated intra-peritoneal metastatic burden. Ongoing projects are aimed toward elucidating the contribution of host factors such as obesity, age, and parity to OvCa metastatic success. We are also examining the role of extracellular vesicles (exosomes, both tumor and host) in these processes. In our oral cancer research, we are currently focused on cancer of the oropharynx associated with human papillomavirus (HPV) infection (HPV-OPSCC). We are using a panel of in vitro analysis together with an ex vivo tonsillar explant model to define the biological function of microRNAs, induced in host cells by an onogenic HPV infection, in progression of OPSCC. Within this framework, understanding the multiple micro-environmental cues that contribute to metastatic success is a major focus of the laboratory.
- 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.
- Waters, M.; Hopf, J.; Tam, E.; Wallace, S.; Chang, J.; Bennett, Z.; Aquino, H.; Roeder, R. K.; Helquist, P.; Stack, M. S. and Nallathamby, P. D. "Biocompatible, Multi-Mode, Fluorescent, T-2 MRI Contrast Magnetoelectric-Silica Nanoparticles (MagSiNs), for on-Demand Doxorubicin Delivery to Metastatic Cancer Cells" 2022 Pharmaceuticals, 15 (10), 1216. DOI: 10.3390/ph15101216.
- Shi, Z. G.; Lopez, J.; Kalliney, W.; Sutton, B.; Simpson, J.; Maggert, K.; Liu, S.; Wan, J. and Stack, M. S. "Development and Evaluation of ActSeq: A Targeted Next-Generation Sequencing Panel for Clinical Oncology Use" 2022 PLOS One, 17 (4), e0266914. DOI: 10.1371/journal.pone.0266914.
- 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.