Kleiderer-Pezold Professor of Chemistry & Biochemistry; Director, Harper Cancer Research Institute
Molecular Tissue and Biophysics
A physical biochemistry course as a graduate student instilled a long-standing interest in molecular biophysics and led to a publication using tools such as analytical ultracentrifugation to probe proteinase:inhibitor interactions (Stack et al., 1987). More recently, we have begun to address changes in tissue biomechanical properties and how this contributes to regulation of biological processes. We have found that Wnt/ß-catenin signaling can be regulated in by integrin-mediated matrix adhesion and is susceptible to alterations in matrix stiffness (for example, by changing collagen concentration or cross-linking collagen), leading to loss of Dkk1, a Wnt inhibitor, and upregulation of the matrix metalloproteinase MT1-MMP (Barbolina et al., 2013). Collaborative studies with the Ravosa laboratory have examined how the biomechanics of mastication of foods with distinct material properties contribute to changes in the bony and cartilaginous structures of the masticatory apparatus (Ravosa et al., 2007 and 2010). Current work is focused on evaluating the unique force environment of the peritoneal cavity and how ascites-induced changes in intra-peritoneal pressure may regulate ovarian cancer metastatic success.
- "Ascites-Induced Compression Alters the Peritoneal Microenvironment and Promotes Metastatic Success in Ovarian Cancer" Asem, M.; Young, A.; Oyama, C.; ClaureDeLaZerda, A.; Liu, Y.; Ravosa, M.J.; Gupta, V.; Jewell, A.; Khabele, D.; Stack, M.S. Sci. Rep. 2020, 10(1), 11913. DOI: 10.1038/s41598-020-68639-2.
- "Modeling the Effects of Ascites-Induced Compression on Ovarian Cancer Multicellular Aggregates" Klymenko, Y.; Wates, R.B.; Weiss-Bilka, H.; Lombard, R.; Liu, Y.; Campbell, L.; Kim, O.; Wagner, D.; Ravosa, M.J.; Stack, M.S. Dis. Model. Mech. 2018, 11(9), pii: dmm034199. DOI: 10.1242/dmm.034199.
- "Matrix Rigidity Activates Wnt Signaling Through Downregulation of Dickkopf-1" Barbolina, M.V.; Liu, Y.; Gurler, H.; Kim, M.; Kajdacsy-Balla, A.A.; Rooper, L.; Shepard, J.; Weiss, M.; Shea, L.D.; Penzes, P.; Ravosa, M.J.; Stack, M.S. J. Biol. Chem. 2013, 288, 141-151.
- "Masticatory biomechanics and masseter fiber-type plasticity" Ravosa, M.J.; Ning, J.; Costley, D.B.; Daniel, A.N.; Stock, S.R.; Stack, M.S. J. Musculoskelet. Neuronal Interact. 2010, 10, 46-55.