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Devon Moose

Mentor:  Michael Henry, PhD

Year Entered Into Program:  2018

Terminal Degree(s) Received: 2021

Research Description

Mechanism of Fluid Shear Stress Resistance in Cancer Cells

During metastasis, the main cause of cancer associated mortality, tumor cells leave their native microenvironment to “seed” distal tissues. Intrinsic to this process is entry into circulation and thus exposure to hemodynamic shear stress within the fluid microenvironment. Initially it was believed that cancer cells are mechanically sensitive to this shear stress; however, recent studies using in vitro models have found that cancer cells display a robust, adaptive resistance to fluid shear stress (FSS). My work on this resistance phenomenon has shown that cancer cells respond to FSS through the activation of RhoA, something that non-transformed cells are unable to do. Additionally, utilizing two different in vivo models, I have demonstrated that 1) cancer cells appear to be more resistant to hemodynamic shear stress and 2) that this resistance is dependent on the RhoA-Myosin II axis. To further explore this resistance mechanism, I am currently evaluating how RhoA is being activated by FSS specifically in cancer cells. Additionally, I am investigating if the adaptive response to FSS is able to increase the efficacy of metastasis. The long-term goal of my research is to discover pathways involved in FSS resistance that have pharmacological interventions to help ameliorate metastatic disease.

Awards

  • Pharmacological and Pharmaceutical Sciences Research Retreat Poster Award, 2018
  • Fellowship appointment on the Pharmacological Sciences Training Program (NIH T32 GM067795), University of Iowa, 2018-2020

Publications

  1. Moose DL, Krog BL, Zhao L, Kim TH, William-Perez S, Burke G, Rhodes L, Vanneste M, Brehney P, Milhem M, Rowat AC, Henry MD.:  Cancer cells resist mechanical destruction in circulation via RhoA/actomyosin-dependent mechano-adaptation. Cell Reports; 30(11):3864-3874, 2020.  PMCID: PMC7219793
  2. Moose DL, Henry MD.:  Survival of the resilient: Mechano-adaptation of circulating tumor cells to fluid shear stress. Mol Cell Oncol. 7(4):1766338, 2020.  PMCID: PMC7469561
  3. Yong C*, Moose DL*, Bannick N, Gutierrez WR, Vanneste M, Svensson R, Breheny P, Brown JA, Dodd RD, Cohen MB, Henry MD.:  Locally invasive, castrate-resistant prostate cancer in a Pten/Trp53 double knockout mouse model of prostate cancer monitored with non-invasive bioluminescent imaging. PLoS One. 15(9):e0232807, 2020.  PMCID: PMC7521703. *Equal Contribution
  4. O’Leary BR, Alexander MS, Du J, Moose DL, Henry MD, Cullen JJ.:  Pharmacological ascorbate inhibits pancreatic cancer metastases via a peroxide-mediated mechanism. Scientific Reports. 10(1):17649, 2020.  PMCID: PMC7572461
  5. Marchal MA, Moose D, Varzavand A, Taylor D, Brown JA, Henry MD, Stipp CS.: Abl kinase deficiency promotes AKT pathway activation and prostate cancer progression and metastasis. Oncogene (in revisions) bioRxiv: https://doi.org/10.1101/2020.05.19.104679
  6. Vanneste M., Huang Q., Li M., Moose D.L., Zhao L., Stamnes, M., Schultz M., Wu M., and Henry M.:  High content screening identifies monensin as an EMT-selective cytotoxic compound. Scientific Reports, 9(1):1200, 2019.
  7. Moose D.L., Krog, B.L., Zhao, L., Kim, T.-H., Williams-Perez, S., Burke, G., Rhodes, L., Vanneste, M., Breheny, P., Milhem, M., Stipp, C.S., Rowat, C.S., Henry, M.D.: Cancer cells resist mechanical destruction in the circulation via RhoA-myosin II axis. uner review at PNAS and published on BioRxiv: 601039, 2019.
  8. Alexander MS, Leary BR, Moose D, Du J, Henry MD, and Cullen JJ.: A model for the detection of pancreatic ductal adenocarcinoma circulating tumor cells. Journal of Biological Methods; 5(3):e97, 2018.  PMCID: PMC6706145
  9. Buchakjian, M.R., Merritt, N.M., Moose, D.L., Dupuy, A.J., Tanas, M.R., and Henry, M.D.:  A Trp53fl/fl Ptenfl/fl mouse model of undifferentiated pleomorphic sarcoma mediated by adeno-Cre injection and in vivo bioluminescence imaging. PLoS One 12:e0183469, 2017.  PMCID: PMC5571905

Research