Department Affiliation: Primary: Cell Biology; Secondary: Pharmacology and Molecular Sciences; Chemical and Biomolecular Engineering
Degree: Ph.D., Yale University School of Medicine
Rank: Associate Professor
Telephone Number: 410-502-2850
Fax Number: 410-955-4129
E-mail address: dnr@jhmi.edu
Home Page URL: www.hopkinsmedicine.org/cellbio/robinson/
School of Medicine Address: 100 Physiology Building, 725 N. Wolfe Street, Baltimore, MD 21205
Understanding Cytokinesis and Cell Shape Control
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. A number of developmental programs are also tightly coupled to cell division, including tissue morphogenesis and stem cell maintenance. However, no cellular process is 100% efficient, and cell division failure is deleterious, leading to tumorigenesis. Therefore, cell division research has significant implications for understanding normal physiology and disease.
We apply a range of genetic, molecular, biochemical, chemical, 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 have demonstrated that myosin-II increases the active, dynamic nature of the living cortex while actin crosslinking proteins control its mechanical resistance. The balance between dynamic rearrangements and resistance determines how cells change shape during cytokinesis.
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 a combination of molecular genetic and micromechanical approaches, we are discerning the contributions from molecular motors, microtubule network, actin-associated proteins, and signaling proteins to mechanosensing during cell division.
Representative 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(17): 1421-1428.
- Kee Y.S. and Robinson D.N. Motor Proteins: Myosin mechanosensors. Curr. Biol. 2008; 18(18): r860-r862.
- 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.
- 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. (Cover article) 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. 17:5275-5286, 2006. Pub Med Reference
- Effler, J.C., Kee, S., Berk, J.M., Tran, M.N., Iglesias, P.A., and Robinson D.N. Mitosis-specific mechanosensing and contractile protein redistribution control cell shape, Curr. Biol. 16:1962-1967, 2006. Pub Med Reference
- Girard, K.D., Kuo, S.C., and Robinson D.N. Dictyostelium myosin-II mechanochemistry promotes active behavior of the cortex on long time-scales, Proc. Natl. Acad. Sci. USA 103:2103-2108, 2006. Pub Med Reference
- Zhang, W. and Robinson D.N. Balance of actively generated contractile and resistive forces controls cytokinesis dynamics, Proc. Natl. Acad. Sci. USA 102:7186-7191, 2005. Pub Med Reference
- Reichl, E.M., Effler, J.C., and Robinson D.N. Stress and strain of cytokinesis, Trends Cell Biol. 15:200-206, 2005. Pub Med Reference
- Girard, K.D., Chaney, C., Delannoy, M., Kuo, S.C., and Robinson D.N. Dynacortin contributes to cortical viscoelasticity and helps define the shape changes of cytokinesis, EMBO J. 23:1536-1546, 2004. Pub Med Reference
- 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(17): 1421-1428.
- Kee Y.S. and Robinson D.N. Motor Proteins: Myosin mechanosensors. Curr. Biol. 2008; 18(18): r860-r862.
- 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.
- 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. (Cover article) 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. 17:5275-5286, 2006. Pub Med Reference
- Effler, J.C., Kee, S., Berk, J.M., Tran, M.N., Iglesias, P.A., and Robinson D.N. Mitosis-specific mechanosensing and contractile protein redistribution control cell shape, Curr. Biol. 16:1962-1967, 2006. Pub Med Reference
- Girard, K.D., Kuo, S.C., and Robinson D.N. Dictyostelium myosin-II mechanochemistry promotes active behavior of the cortex on long time-scales, Proc. Natl. Acad. Sci. USA 103:2103-2108, 2006. Pub Med Reference
- Zhang, W. and Robinson D.N. Balance of actively generated contractile and resistive forces controls cytokinesis dynamics, Proc. Natl. Acad. Sci. USA 102:7186-7191, 2005. Pub Med Reference
- Reichl, E.M., Effler, J.C., and Robinson D.N. Stress and strain of cytokinesis, Trends Cell Biol. 15:200-206, 2005. Pub Med Reference
- Girard, K.D., Chaney, C., Delannoy, M., Kuo, S.C., and Robinson D.N. Dynacortin contributes to cortical viscoelasticity and helps define the shape changes of cytokinesis, EMBO J. 23:1536-1546, 2004. Pub Med Reference
Other graduate programs in which Dr. Robinson participates:
Anti-Cancer Drug Development Program
Biochemistry, Cellular and Molecular Biology (BCMB)
NanoBioMed (NBMed)
