Cell division is essential for growth and replenishment of tissues and organs and to achieve this renewal, the human body has nearly a billion cell division events underway at every moment in time. However, no cellular process is 100% efficient, and cell division failure is deleterious, leading to tumorigenesis. We apply a range of genetic, molecular, chemical, biochemical, biophysical, and engineering methods to discover new factors involved in cytokinesis and to learn how they contribute to the process. By combining these approaches, we are developing a sophisticated understanding of how myosin-II motor proteins and actin crosslinking proteins govern cell shape changes. We are also identifying the signaling pathways that regulate cellular contractility and cell shape changes.

Recently, we discovered a novel mechanosensory system that allows dividing cells to sense shape perturbations so that the cells can correct the disturbance and complete cytokinesis normally. Mechanosensing is fundamental to a wide variety of cellular processes critical to healthy and pathological states. Tumor cells can grow in the absence of surface attachment, a feature that classically defines cellular transformation, indicating that changes in mechanotransduction are an important part of cancer progression. Bone remodeling, blood pressure regulation, and hearing are all examples of normal processes that depend on mechanosensing. Yet, the cellular and molecular mechanisms of mechanosensing are not well understood in any system. Using molecular genetics in combination with micromechanical approaches, we are discerning the contributions from molecular motors, microtubule network, actin-associated proteins, and signaling proteins to mechanosensing during cell division.

Publications:

Ren Y., Effler J.C., Norstrom M., Luo T., Firtel R.A., Iglesias P.A., Rock, R.S. and Robinson D.N. Mechanosensing through cooperative interactions between myosin-II and the actin crosslinker cortexillin-I. Curr. Biol. 2009; 19: In press.

Yang L., Effler J.C., Kutscher B.L., Sullivan S.P., Robinson D.N. and Iglesias P.A. Modeling cellular deformations using the level set formalism. BMC Systems Biology 2008; 2:68.Pub Med Reference

Reichl E.M., Ren Y., Morphew M.K., Delannoy M., Effler J.C., Girard K.D., Divi S., Iglesias P.A., Kuo S.C. and Robinson D.N. Interactions between myosin and actin crosslinkers control cytokinesis contractility dynamics and mechanics. Curr. Biol. 2008; 18(7): 471-480.Pub Med Reference

Kabacoff C., Xiong Y., Musib R., Reichl E.M., Kim J., Iglesias P.A., Robinson D.N. Dynacortin facilitates polarization of chemotaxing cells. BMC Biol. 2007; 5:53.Pub Med Reference

Octtaviani E., Effler J.C., and Robinson D.N. Enlazin, a natural fusion of two classes of canonical cytoskeletal proteins, contributes to cytokinesis dynamics. Mol. Biol. Cell. 2006; 17(12): 5275-5286.Pub Med Reference