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Khuloud Jaqaman

Education

Ph.D., Indiana University Bloomington, 2003
B.Sc., Birzeit University (West Bank), 1998

Research Interests

A central question in cell signaling is where, when and how signals are spatially and temporally organized. Research over the last two decades has been providing evidence that the plasma membrane plays a central role in the spatiotemporal organization of cell signaling and decision making. Most notably, there is indirect evidence from structural, biochemical and fixed cell studies that horizontal interactions between receptors in the plasma membrane are an essential step in organizing transmembrane signal transduction. In addition, the membrane is organized into specialized microdomains, such as lipid rafts, focal adhesions and cytoskeleton-mediated compartments, which sort receptors, bring them together in various combinations, and separate them from each other. These microdomains can spatially control signaling activation by, and cellular sensitivity to, extracellular cues.

To determine the interplay between these different factors and establish their collective regulation of cell signaling, I am taking an integrative approach combining single-molecule live-cell imaging, computer vision and mathematical modeling. This assay allows us to observe discrete aggregation and dissociation events between individual receptors, and to accurately measure their kinetics. Combining this assay with system perturbations, such as RNAi-mediated protein depletion and/or pharmacological perturbations, allows us to elucidate the role of membrane microdomains in regulating receptor aggregation kinetics and thus in organizing signal transduction, and allows us to explore the hetero-interactions between co-receptors that are essential for their function.

As a first system, I am studying the aggregation of the scavenger receptor CD36 in human macrophages, where we have discovered that the cytoskeleton controls the dimensionality of receptor diffusion in the membrane in order to increase the probability of receptor encounters and aggregation. I plan to expand this work to the study of CD36 in human microvascular endothelial cells, where CD36 has been shown to be a receptor for thrombospondin-1 (TSP-1), causing endothelial cell apoptosis via its aggregation upon TSP-1 binding.

Publications

Jaqaman K., Kuwata H., Touret N., Collins R., Trimble W.S., Danuser G., Grinstein S. Cytoskeletal Control of CD36 Diffusion Propotes its Receptor and Signaling Function. Cell, 146: 593-606. 2011.

Loerke D., Mettlen M., Yarar D., Jaqaman K., Jaqaman H., Danuser G., and Schmid S. L., Cargo and dynamin regulate clathrin-coated pit maturation. PLoS Biology, 7: e57. 2009.

Jaqaman K., Loerke D., Mettlen M., Kuwata H., Grinstein S., Schmid S. and Danuser G., Robust single particle tracking in live cell time-lapse sequences. Nat. Methods 5: 695 – 702. 2008. Cover Story.

Jaqaman K., Dorn J. F., and Danuser G., From live cell microscopy to molecular mechanisms: deciphering the functions of kinetochore proteins. Chapter 9. Imaging Cellular and Molecular Biological Function, Eds. Fischknecht F. and Shorte S. pp. 265 – 288. Springer, Heidelberg. 2007.

Jaqaman K.*, Dorn J. F.*, Marco E., Sorger, P. K. and Danuser G., Phenotypic clustering of yeast mutants based on kinetochore microtubule dynamics. Bioinformatics 23: 1666 – 1673. 2007. (* equal contribution).

Jaqaman K. and Danuser G., Linking data to models: data regression. Nat. Rev. Mol. Cell Biol. 7: 813 – 819. 2006.

Jaqaman K., Dorn J. F., Jelson, G., Tytell J. D., Sorger, P. K. and Danuser G., Comparative autoregressive moving average analysis of kinetochore microtubule dynamics in yeast. Biophys. J. 91: 2312 – 2325. 2006.

Dorn J. F., Jaqaman K., Rines D. R., Jelson G. S., Sorger P. K. and Danuser G., Yeast kinetochore microtubule dynamics analyzed by high-resolution three-dimensional microscopy. Biophys. J. 89: 2834 – 2854. 2005.

Jaqaman K., Tuncay K. and Ortoleva P. J., Classical density functional theory of orientational order at interfaces: Application to water. J. Chem. Phys. 120: 926 – 938. 2004.

Jaqaman K. and Ortoleva P. J., New space warping method for the simulation of large-scale macromolecular conformational changes. J. Comp. Chem. 23: 484 – 491. 2002.

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