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Douglas N. Robinson
Department Affiliation: Primary: Cell Biology; Joint: Medicine; Secondary: Pharmacology and Molecular Sciences; Chemical and Biomolecular Engineering
Degree: Ph.D., Yale University School of Medicine
Telephone Number: 410-502-2850
Fax Number: 410-955-4129
E-mail address: email@example.com
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
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 of breast cancer cells. In this case, we found that cancer and non-cancer cells can compete with each other, and due to their unique mechanical properties, the cancer cell (winner cell) can often engulf and kill the non-cancer cell (loser 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 many of 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.
- 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. 19(17): 1421-1428, 2009. Pub Med Reference
- Larson S.M., Lee H.J., Hung, P.-h., Matthews, L.M., Robinson D.N., and Evans J.P. Cortical mechanics and meiosis II completion in mammalian oocytes are mediated by myosin-II and ezrin-radixin-moesin (ERM) proteins. Mol. Biol. Cell 21:3182-3192, 2010. Pub Med Reference
- Zhou, Q., Kee, Y.-S., Poirier, C.C., Jilenik, C., Osbome, J., Divi, S., Surcel, A., Tran, M.E., Eggert, U.S., Müller-Taubenberger A., Iglesias P.A., Cotter R.J., and Robinson D.N. 14-3-3 coordinates microtubules, Rac, and myosin II to control cell mechanics and cytokinesis. Curr. Biol. 20:1881-1889, 2010. Pub Med Reference
- Luo, T., Mohan, K., Srivastava, V., Ren, Y., Iglesias, P.A., Robinson, D.N. Understanding the cooperative interactions between myosin II and actin crosslinkers mediated by actin filaments during mechanosensation. Biophys. J. 102(2): 238-247, 2012. Pub Med Reference
- Kee, Y.S., Ren, Y., Dorfman, D., Iijima, M., Firtel, R.A., Iglesias, P.A., Robinson, D.N. A mechanosensory system governs myosin II accumulation in dividing cells. Mol. Biol. Cell 23(8): 1510-1523, 2012. Pub Med Reference
- Poirier, C.C., Ng, W.P., Robinson, D.N., Iglesias, P.A. Deconvolution of the cellular force-generating subsystems that govern cytokinesis furrow ingression. PLoS Comp. Biol. 8(4): e1002467, 2012. Pub Med Reference
- Dickinson, D., Robinson D.N., Nelson, W.J., Weis, W.I. α-catenin and IQGAP regulate myosin localization to control epithelial tube morphogenesis in Dictyostelium. Dev. Cell 23:533-546, 2012. Pub Med Reference
- Robinson, D.N., Iglesias, P.A. Bringing the physical sciences into your cell biology research. Mol. Biol. Cell 23(21): 4167-4170, 2012. Pub Med Reference
Kabacoff C, Srivastava V, Robinson DN. A Summer Academic Research Experience for Disadvantaged Youth. CBE Life Sci. Educ. 2013; In press.
Other graduate programs in which Dr. Robinson participates: