The Cell Migration in Disease Group at the Center for Engineering in Medicine is working to define the normal course of cell movement, and to identify how that movement changes as a result of disease.
All cells in our body have the ability to move, a critical feature in many health and disease situations. However, cell motility is rarely random. Most often, cells can follow directional cues in the form of chemical stimuli (aka chemotaxis). For example, white blood cells (leukocytes) are able to follow gradients of signaling molecules diffusing from sites of acute or chronic inflammation.
Less often, cells can move along heterogeneous structures in tissues (aka mechanotaxis). For example, cancer cells can spread away from the primary tumor by following the trajectories of lymphatic vessels, nerves and white matter tracts. Understanding how they could accomplish such complex tasks might reveal new ways to control cell motility for therapeutic purposes in inflammatory and degenerative diseases or cancer.
To gain useful insights into the mechanisms of cell motility, we started by designing new tools to allow us to measure the directionality and speed characteristics of moving cells. We can now do this with unprecedented precision and we made several unexpected observations.
We defined for the first time a set of “normal values” for directional decisions and speed in neutrophils from healthy people. We measured how neutrophil speed is temporarily decreased after burn injuries, favoring infections. We showed that cancer cells can be persistently guided over hundreds of microns in one direction along microscale structures.
Ultimately, all these new findings will converge towards new therapeutic strategies for modulating the motility of various cells, in a broad range of conditions that span from acute sepsis to chronic inflammation and from cancer invasion to tissue regeneration.
Ongoing research projects:
- Microfluidic assays to quantify neutrophil motility in burn patients during sepsis
- Cancer cell migration in confined microfabricated environments and through mazes
- Neutrophil retrotaxis during chronic inflammation
- Microfluidic assays to study the modulation of microglia migration in Alzheimer's disease
- Lee, Jungwoo, Matthew Li, Jack Milwid, Joshua Dunham, Claudio Vinegoni, Rostic Gorbatov, Yoshiko Iwamoto, Fangjing Wang, Keyue Shen, Kimberley Hatfield, Marianne Enger, Sahba Shafiee, Emmet McCormack, Benjamin L. Ebert, Ralph Weissleder, Martin L. Yarmush, and Biju Parekkadan. "Implantable microenvironments to attract hematopoietic stem/cancer cells." Proceedings of the National Academy of Sciences 109, no. 48 (2012): 19638-19643.
- Desai, Salil P., Sangeeta N. Bhatia, Mehmet Toner, and Daniel Irimia. "Mitochondrial localization and the persistent migration of epithelial cancer cells." Biophysical journal 104, no. 9 (2013): 2077-2088.
- Prentice-Mott, Harrison V., Chi-Han Chang, L. Mahadevan, Timothy J. Mitchison, Daniel Irimia, and Jagesh V. Shah. "Biased migration of confined neutrophil-like cells in asymmetric hydraulic environments." Proceedings of the National Academy of Sciences 110, no. 52 (2013): 21006-21011.Mitochondrial Localization and the Persistent Migration of Epithelial Cancer cells
- Nery, Flavia C., Cintia C. da Hora, Nadia A. Atai, Edward Y. Kim, Jasmin Hettich, Thorsten R. Mempel, Xandra O. Breakefield, and Daniel Irimia. "Microfluidic platform to evaluate migration of cells from patients with DYT1 dystonia." Journal of neuroscience methods 232 (2014): 181-188.
- Robertson, Anne L., Geoffrey R. Holmes, Aleksandra N. Bojarczuk, Joseph Burgon, Catherine A. Loynes, Myriam Chimen, Amy K. Sawtell, Bashar Hamza, Joseph Willson, Sarah R. Walmsley, Sean R. Anderson, Mark C. Coles, Stuart N. Farrow, Roberto Solari, Simon Jones, Lynne R. Prince, Daniel Irimia, G. Ed Rainger, Visakan Kadikamanathan, Moira K. B. Whyte and Stephen A. Renshaw. "A zebrafish compound screen reveals modulation of neutrophil reverse migration as an anti-inflammatory mechanism." Science translational medicine 6, no. 225 (2014): 225ra29-225ra29.