Faculty & Research
|School of Medicine Address||Johns Hopkins University School of Medicine|
725 Wolfe St., 100 Physiology
Baltimore MD 21205
|Link to Lab Homepage|
Research Topic: Cytokinesis and Cell Shape Control
Multi-cellular living organisms grow from single cells into multicellular, complex systems composed of highly diverse cell-types organized into tissues, which in turn form organs and organ systems. To organize and maintain this complex architecture, the organism must undergo constant renewal through cell proliferation and elimination of unwanted cells. This process of tissue development and homeostasis requires chemical and mechanical information to be sensed by the cells within the tissues, and in turn, interpreted to guide their decision making: to divide, migrate, constrict, or die. Failure in these processes lead to diverse diseases, such as hypertension, degeneration, and cancer.
We have been studying cytokinesis (cell division) as a model cell behavior that incorporates internally generated signals with external mechanical cues to drive healthy cell shape change. We have discerned the mechanics that drive this process, and identified how the cell senses external forces (mechanosensing) and transmits them to changes in the chemical signaling pathways that guide cytokinesis. While we continue to study how these processes direct cytokinesis, we are also learning how these same principles apply to diseases such as cancer. For example, we have identified how mechanical cues guide aberrant behaviors in breast cancer. In this case, we found that cancer and non-cancer cells compete with each other, and due to their unique mechanical properties, the cancer cell can engulf and kill the non-cancer cell.
In another project, we are exploring how cellular growth control pathways lead to defects in cell mechanics. In particular, a key regulatory pathway, which guides liver formation and leads to liver cancer if the pathway becomes uncontrolled, also controls the hepatocyte mechanical properties. Finally, we have found that these same principles apply to the development of a mammalian egg where disruption of the cell mechanics machinery causes defects in the formation of a healthy egg. Such mechanics defects could contribute to some types of human infertility and/or birth defects.
Luo T, Mohan K, Srivastava V, Ren Y, Iglesias PA, Robinson DN. Understanding the cooperative interactions between myosin II and actin crosslinkers mediated by actin filaments during mechanosensation. Biophys. J. 2012; 102(2): 238-247.
Kee YS, Ren Y, Dorfman D, Iijima M, Firtel RA, Iglesias PA, Robinson DN. A mechanosensory system governs myosin II accumulation in dividing cells. Mol. Biol. Cell 2012; 23(8): 1510-1523.
Poirier CC, Ng WP, Robinson DN, Iglesias PA. Deconvolution of the cellular force-generating subsystems that govern cytokinesis furrow ingression. PLoS Comp. Biol. 2012; 8(4): e1002467.
Dickinson D, Robinson DN, Nelson WJ, Weis WI. α-catenin and IQGAP regulate myosin localization to control epithelial tube morphogenesis in Dictyostelium. Dev. Cell 2012; 23: 533-546.
Robinson DN, Iglesias PA. Bringing the physical sciences into your cell biology research. Mol. Biol. Cell 2012; 23(21): 4167-4170.
Zhou Q, Kee Y-S, Poirier CC, Jelinek C, Osborne J, Divi S, Surcel A, Tran ME, Eggert US, Müller-Taubenberger A, Iglesias PA, Cotter RJ, Robinson DN. 14-3-3 coordinates microtubules, Rac, and myosin II to control cell mechanics and cytokinesis. Curr. Biol. 2010; 20:1881-1889.
Ren Y, Effler JC, Norstrom M, Luo T, Firtel RA, Iglesias PA, Rock RS and Robinson DN.
Mechanosensing through cooperative interactions between myosin-II and the actin crosslinker cortexillin-I. Curr. Biol. 2009; 19.PubMed Reference
Yang L, Effler JC, Kutscher BL, Sullivan SP, Robinson DN and Iglesias PA. Modeling cellular deformations using the level set formalism. BMC Systems Biology 2008; 2:68.
Reichl EM, Ren Y, Morphew MK, Delannoy M, Effler JC, Girard KD, Divi S, Iglesias PA, Kuo SC and Robinson DN. Interactions between myosin and actin crosslinkers control cytokinesis contractility dynamics and mechanics. Curr. Biol. 2008; 18(7): 471-480.
Kabacoff C, Xiong Y, Musib R, Reichl EM, Kim J, Iglesias PA, Robinson DN. Dynacortin facilitates polarization of chemotaxing cells. BMC Biol. 2007; 5:53.
Octtaviani E, Effler JC, and Robinson DN. Enlazin, a natural fusion of two classes of canonical cytoskeletal proteins, contributes to cytokinesis dynamics. Mol. Biol. Cell. 2006; 17(12): 5275-5286.