Biomechanics, 3D tissue engineering, cancer
The current standard of care for bone metastasis is therapies targeting the cells that degrade bone. These cells are directed by cancer cells to degrade bone in order to release pro-tumorigenic growth factors stored within the skeletal extracellular matrix. These therapies are not curative and do not halt metastasis-mediated bone degradation, indicating additional factors contribute to bone degradation. My research program focuses on the skeletal mechanical environment and its regulation of cancer.
Specifically, we investigate 1) the skeleton’s mechanical environment and its regulation of the remodeling process, and 2) the role of cells along the osteogenic lineage, which comprise the principal sensor and effector cells of mechanical cues, in metastatic processes. My long-term goal is to identify novel therapeutic targets for treating and preventing bone metastases as well as cancer-associated reductions in bone strength. My experimental approach uses novel in vivo and in vitro mechanical loading model systems to correlate cellular function with cancer pathogenesis, tissue-level changes in tumor burden, and skeletal tissue strength.
- Wang W, Sarazin BA, Kornilowicz G, Lynch ME. “Mechanically-loaded breast cancer cells modify osteocyte mechanosensitivity by secreting factors that increase osteocyte dendrite formation and downstream resorption.” Frontiers in Endocrinology, invited submission for Cancer and Bone Metastasis Special Research Topic. doi: 10.3389/fendo.2018.00352.
- Liu B, Han S, Modarres-Sadeghi Y, Lynch ME. “Perfusion applied to a 3D model of bone metastasis results in evenly dispersed mechanical stimuli.” Biotechnology & Bioengineering, 115(4):1076-1085, 2017. doi: 10.1002/bit.26524.
- Lynch ME, Chiou AE, Lee MJ, Polamraju P, Marcott SC, Lee Y, Fischbach C. “3D mechanical loading modulates the osteogenic response of mesenchymal stem cells to tumor-derived soluble signals.” Tissue Engineering Part A. 22:1006-15, 2016. doi:10.1089/ten.tea.2016.0153.
- Lynch ME and Fischbach C. “Biomechanical forces in the skeleton and their relevance to bone metastasis: biology and engineering considerations.” Invited Review for Advanced Drug Delivery Reviews, 79-80: 119-34, 2014. doi: 10.1016/j.addr.2014.08.009.
- Lynch ME, Brooks DJ, Mohanan S, Lee MJ, Polamraju P, Dent KC, Bonassar L, van der Meulen MCH, Fischbach C. “In Vivo Tibial Compression Decreases Osteolysis and Tumor Formation in a Human Breast Cancer Metastasis Model.” Journal of Bone and Mineral Research, 28: 2357-2367, 2013. doi: 10.1002/jbmr.1966.