Mechanopathologies & Host Organs
Tumor mechanical forces – including interstitial fluid pressure and solid stress – are exerted not only within the tumor microenvironment, but externally on the surrounding tissue as well. In sensitive host organs such as the brain, these forces can wreak havok by displacing and compressing surrounding blood vessels and neuronal cells, resulting in neurological dysfunction. By developing experimental mechanical testing systems, such as the compressive cranial window, it is possible to causally and optically dissect how tumor mechanics damage the surrounding tissue. Translational approaches preventing or reversing the detrimental effects of tumor mechanopathologies on host organ health and function may augment patient response and performance during anti-cancer treatments.
Publications
Onwudiwe K.*, Najera J.*, Holen L., Burchett A.A., Rodriguez D., Zarodniuk M., Siri S., and Datta M.# “Single-cell mechanical analysis reveals viscoelastic similarities in normal and neoplastic brain cells,” Biophysical Journal, E-pub ahead of print: https://www.cell.com/biophysj/fulltext/S0006-3495(24)00215-7. (* = equal contributions; # = corresponding author.)
Najera J., Rosenberger M.R., and Datta M.# (2023) “Atomic force microscopy methods to measure tumor mechanical properties,” Cancers, 15: 3285.
Zarodniuk M., Steele A., Lu X., Li J., and Datta M.# “CNS tumor stroma transcriptomics identify perivascular fibroblasts as predictors of immunotherapy resistance in glioblastoma patients,” npj Genomic Medicine, E-pub ahead of print: https://www.nature.com/articles/s41525-023-00381-w. (# = corresponding author.)
Holen L.*, Onwudiwe K.*, Najera J., Zarodniuk M., Obayemi J.D., Soboyejo W.O., and Datta M.# (2023) “Shear assay protocol for the determination of single-cell material properties,” Journal of Visualized Experiments, E-pub ahead of print: https://www.jove.com/t/65333/shear-assay-protocol-for-determination-single-cell-material. (* = equal contributions; # = corresponding author.)
Zhang S.*, Regan K.*, Najera J.*, Chu V., Grinstaff M.W., Datta M.#, and Nia H.T.# “The peritumor microenvironment: physics and immunity,” Trends in Cancer, E-pub ahead of print: https://authors.elsevier.com/a/1h1a98Z12yTuSQ. (* = equal contributions)
Datta M.#, Chatterjee S., Perez E.M., Gritsch S., Roberge S., Duquette M., Chen I.X., Naxerova K., Kumar A.S., Ghosh M., Emblem K.E., Ng M.R., Ho. W.W., Kumar P., Krishnan S., Dong X., Speranza M.C., Neagu M.R., Reardon D.A., Sharpe A.H., Freeman G.J., Suva M.L.#, Xu L.#, Jain R.K.# (2023) “Losartan controls immune checkpoint blocker-induced edema and improves survival in glioblastoma,” E-pub ahead of print: https://www.pnas.org/eprint/MP69MI2GBHTY9VJKDSBQ/full. (# = corresponding author(s).)
Datta M. (2022) “Studying the tumor microenvironment under pressure,” Immuno-Oncology Insights, 3: 339-344.
Onwudiwe K., Burchett A.A., and Datta M.# (2022) “Mechanical and metabolic interplay in the brain metastatic microenvironment,” Frontiers in Oncology, E-pub ahead of print: https://www.frontiersin.org/articles/10.3389/fonc.2022.932285/full.
Nia H.T.*, Datta M.*, Seano G.*, Ho W.W., Roberge S., Huang P., Munn L.L. and Jain R.K. (2020) “In vivo compression and imaging in mouse brain to measure the effects of solid stress,” Nature Protocols, 15: 2021-2340. (* = equal contributions.) Featured in Nature Community.
Seano G.*, Nia H.T.*, Emblem, K.E.*, Datta M., Ren J., Krishnan S., Kloepper J., Pinho M.C., Ho W.W., Ghosh M., Askoxylakis V., Ferraro G.B., Riedemann L., Gerstner E.R., Batchelor T.T., Wen P.Y., Lin N.U., Grodzinksy A.J., Fukumura D., Huang P., Basish J.W., Padera T.P., Munn L.L., and Jain R.K. (2019) “Solid stress in brain tumours causes neuronal loss and neurological dysfunction and can be reversed by lithium,” Nature Biomedical Engineering, 3: 230-245. (* = equal contributions.) Featured in Nature Research Bioengineering Community, Neuroscience News, EurekAlert, and Medical Xpress.
Nia H.T.*, Datta M.*, Seano G., Munn L.L., and Jain R.K. (2018) “Quantifying solid stress and elastic energy from excised or in situ tumors,” Nature Protocols 13: 1091-1105. (* = equal contributions.)
Nia H.T., Seano G., Liu H., Datta M., Jones D., Rahbari N., Incio J., Chauhan V.P., Jung K., Martin J.D., Askoxylakis V., Padera T.P., Fukumura D., Boucher Y., Hornicek F.J., Grodzinsky A.J., Baish J.W., Munn L.L., and Jain R.K. (2016) “Solid stress and elastic energy as measures of tumor mechanopathology,”Nature Biomedical Engineering 1: 1-11. Featured in Nature News and Views, Nature Reviews Clinical Oncology, Harvard Medical School News & Research, Medical Xpress, and EurekAlert.