the DeSimone Laboratory at the University of Virginia
We study the emergence of
Our research interest is morphogenesis; we are working to uncover cellular and molecular mechanisms involved in generating the proper three-dimensional organization of embryos and tissues. We focus primarily on cellular movements required for gastrulation and neurulation using embryos from the amphibian Xenopus laevis.
...the role of cell-cell and cell-ECM adhesion in this process...
Precise spatiotemporal regulation of cell adhesion and adhesion-dependent cell signaling is required for the coordination of directed cell movements and the establishment of cell and tissue polarity. Embryonic extracellular matrices (ECMs) serve to define compartments within which cell movements are confined and regulated.
...and how mechanical forces influence development.
In recent years our studies have focused increasingly on the signaling "crosstalk" between stressed cadherin adhesions at cell-cell interfaces and integrin adhesions to the ECM. We have determined that tugging forces on cadherin adhesions are required to establish the polarized protrusions of collectively migrating cells on fibronectin. Current research seeks to elucidate the instructive importance of mechanical cues in directing not only morphogenetic behaviors but also gene expression.
Cadherin adhesion, tissue tension, and noncanonical wnt signaling regulate fibronectin matrix organization
Dzamba, B., Jakab, K.R., Marsden, M., Schwartz, M.A., and DeSimone, D.W.
(2009) Developmental Cell 16, 421-432
A Mechanoresponsive cadherin-keratin complex directs polarized protrusive behavior and collective cell migration
Weber, G.F., Bjerke, M.A., and DeSimone, D.W.
(2012) Developmental Cell 22, 104-115
Mechanical and signaling roles for keratin intermediate filaments in the assembly and morphogenesis of Xenopus mesendoderm tissue at gastrulation
Sonavane, P.R., Wang, C., Dzamba, B., Weber, G.F., Periasamy, P. and DeSimone D.W.
(2017) Development 144, 4363-4376
Present and Past
Ivy Foundation Pratt Distinguished Professor of Morphogenesis, Principal Investigator
Doug has been interested in the problem of morphogenesis for more than 35 years. As a grad student with Mel Spiegel, he described blastomere lineage-specific differences in cell surface protein expression in sea urchin embryos. While a postdoc with Richard Hynes at MIT, he and his colleagues provided the first molecular characterization of integrin receptors. Since coming to UVA his lab has used Xenopus embryos to investigate the roles of extracellular matrix proteins, integrins and cadherins in cell adhesion and migration. His current focus is to uncover the roles mechanical forces play in adhesion-dependent cell-signaling, morphogenesis and cell-fate determination.
Bette was first introduced to extracellular matrix as a high school student intern at Ciba-Geigy corporation where she spent her summer sectioning arthritic rabbit knees. In graduate school at the University of Wisconsin, and then as a postdoc at Shriners Hospital in Portland, Oregon, she became fascinated by the question of how cells assemble and interact with their extracellular matrix. She joined Doug’s lab in order to study the dynamics of the matrix during the complex morphogenetic cell and tissue movements of early embryogenesis.
Dave is in interested in how morphogenic machines work. He spent several years in the Keller lab investigating how cell movements generate morphogenic shape changes and how groups of cells work together to generate the forces that drive these changes. In the DeSimone lab, he has taken this to the next (smaller-scale) level, and is working to understand the cell biology underlying the biomechanics of morphogenic machines.
Kara "makes it all possible" by taking exceptionally good care of our frog colony. She also manages the lab, orders our stuff, keeps us in line with "Slack", and frequently supplies us with candy.
Graham is a recent graduate of the University of Virginia (class of 2019) and the latest member of the DeSimone lab. He is continuing studies begun as an undergrad to address the biomechanical properties of collectively migrating mesendoderm cells. He has a talent for the delicate micro dissections required to obtain and culture mesendoderm tissue in vitro. Graham is using these skills to ask whether the keratin intermediate filament cytoskeleton functions as a supracellular elastic network during collective cell migration.
Sampson brings nearly 3 years of squirrel chasing experience to the lab. His primary goal is to one day catch a squirrel. When not pursuing varmints, Sampson likes to unwind with the PI.
Predocs - Postdocs - Support Staff
Charles A. Whittaker
Sandra J. Kateeshock
Department of Cell Biology
University of Virginia
P.O. Box 800732, School of Medicine
Charlottesville, VA 22908
Pinn Hall, room 3229
1340 Jefferson Park Avenue
38o 1' 54.642" N
78o 30' 1.9296" W