Sharon Stack

Sharon Stack

Mechanisms of Metastasis

Biography

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

Selected Awards

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

Research Interests

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.

Recent Papers

  • Asem, M., Young, A. M., Oyama, C., De La Zerda, A. C., Liu, Y., Yang, J., Hilliard, T. S., Johnson, J., Harper, E. I., Guldner, I., Zhang, S., Page-Mayberry, T., Kaliney, W. J., 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.
  • Harper, E. I., Sheedy, E. F., Stack, M. S. "With great age comes great metastatic ability: Ovarian cancer and the appeal of the aging peritoneal microenvironment" 2018 Cancers, 10 (7), DOI:10.3390/cancers10070230.
  • 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.
  • Klymenko, Y., Kim, O., Loughran, E., Yang, J., Lombard, R., Alber, M., Stack, M. S. "Cadherin composition and multicellular aggregate invasion in organotypic models of epithelial ovarian cancer intraperitoneal metastasis" 2017 Oncogene, 36 (42), pp. 5840-5851. DOI:10.1038/onc.2017.171.
  • Yang, J., Kasberg, W. C., Celo, A., Liang, Z., Quispe, K., Sharon Stack, M. "Post-translational modification of the membrane type 1 matrix metalloproteinase (MT1-MMP) cytoplasmic tail impacts ovarian cancer multicellular aggregate dynamics" 2017 Journal of Biological Chemistry, 292 (32), pp. 13111-13121. DOI:10.1074/jbc.M117.800904.
  • Johnson, J. J., Miller, D. L., Jiang, R., Liu, Y., Shi, Z., Tarwater, L., Williams, R., Balsara, R., Sauter, E. R., Stack, M. S. "Protease-activated Receptor-2 (PAR-2)-mediated Nf-κB activation suppresses inflammation-associated tumor suppressor MicroRNAs in oral squamous cell carcinoma" 2016 Journal of Biological Chemistry, 291 (13), pp. 6936-6945. DOI:10.1074/jbc.M115.692640.

Contact Information

  • Kleiderer-Pezold Professor of Biochemistry; Ann F. Dunne & Elizabeth Riley Director, Harper Cancer Research Institute
  • Office: A200D Harper Hall
  • Phone: 574-631-2518
  • Send an email
  • Visit Website

Primary Research Areas

Research Specialties