Department of Chemistry & Biochemistry

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 Publications

• 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.
• Bahcecioglu, G.; Yue, X. S.; Howe, E.; Guldner, I.; Stack, M. S.; Nakshatri, H.; Zhang, S. Y. and Zorlutuna, P. "Aged Breast Extracellular Matrix Drives Mammary Epithelial Cells to an Invasive and Cancer-Like Phenotype" 2021 Advanced Science, 8 (22), 2100128. DOI: 10.1002/advs.202100128.
• Carey, P.; Low, E.; Harper, E. and Stack, M. S. "Metalloproteinases in Ovarian Cancer" 2021 International Journal of Molecular Sciences, 22 (7), 3403. DOI: 10.3390/ijms22073403.
• Mondal, T.; Shivange, G. N.; Tihagam, R.; Lyerly, E.; Battista, M.; Talwar, D.; Mosavian, R.; Urbanek, K.; Rashid, N. S.; Harrell, J. C.; Bos, P. D.; Stelow, E. B.; Stack, M. S.; Bhatnagar, S. and Tushir-Singh, J. "Unexpected PD-L1 Immune Evasion Mechanism in TNBC, Ovarian, and Other Solid Tumors by DR5 Agonist Antibodies" 2021 EMBO Molecular Medicine, 13 (3), e12716. DOI: 10.15252/emmm.202012716.
• 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.