Khuloud Jaqaman, Ph.D.

Khuloud Jaqaman

Instructor

Department of Systems Biology
Harvard Medical School
200 Longwood Avenue, WAB444
Boston, MA 02115

(617) 432-7942
khuloud_jaqaman [at] hms.harvard.edu

Research

The overall goal of my research is to develop integrative approaches combining live-cell imaging, computer vision and mathematical modeling to elucidate the functional interactions between proteins for the regulation of cellular processes.

My current focus is on investigating the spatiotemporal organization of receptors in the plasma membrane to establish the mechanisms initiating cell signaling. To achieve this, I am developing quantitative single-molecule live-cell imaging techniques, including mathematical tools that allow the derivation of population information from single molecule experiments and the computational multiplexing of data from multiple experiments to overcome the limitation of imaging only 1 or 2 molecular species at a time.

In a first project, started during my postdoctoral work in the Danuser lab, I focused on the receptor CD36 in macrophages (with S. Grinstein, Hospital for Sick Children, Toronto). For this I developed a particle tracking algorithm that can follow particles in dense receptor fields and capture their clustering events, a challenge in single molecule imaging (Jaqaman et al., Nat. Methods 2008). With the help of this particle tracking algorithm, we found that CD36 dynamics in the membrane are regulated by the cytoskeleton in a manner that enhances unligated receptor clustering, thus priming macrophages to respond when exposed to ligand (Jaqaman et al., Cell 2011).

Building on these discoveries and technological advances, I am currently working on two projects:
(1) Single molecule study of CD36 and beta1-integrin to establish how they initiate anti-angiogenic signaling upon binding to thrombospondin-1 (with Nicolas Touret, U. of Alberta, Edmonton).
(2) Live-cell photoactivated localization microscopy of integrin to investigate the relationship between integrin dynamics at the single molecule level and edge protrusion dynamics at the cellular level (with Catherine and James Galbraith, NIH/NIDCR).

Education

Postdoctoral fellow, Cell Biology
The Scripps Research Institute
Advisor: Gaudenz Danuser

Ph. D., Biophysics
Indiana University Bloomington
Advisor: Peter. J. Ortoleva

B. Sc., Physics
Birzeit University, West Bank

Publications

  • Jaqaman K.*, Kuwata H.*, Touret N., Collins R., Trimble W. S., Danuser G. and Grinstein S., Cytoskeletal control of CD36 diffusion promotes its receptor and signaling function. Cell 146: 593 – 606. 2011. (* equal contribution).
  • Flannagan R. S., Harrison R. E., Yip C. M., Jaqaman K. and Grinstein S., Dynamic macrophage “probing” is required for the efficient capture of phagocytic targets. J. Cell. Biol. 191: 1205 – 1218. 2010.
  • Jaqaman K.*, King E. M.*, Amaro A. C.*, Winter J. R.*, Dorn J. F., Elliott H. L., Mchedlishvili N., McClelland S. E., Porter I. M., Posch M., Toso A., Danuser G., McAinsh A. D., Meraldi P. and Swedlow J. R., Kinetochore alignment within the metaphase plate is regulated by centromere stiffness and microtubule depolymerases. J. Cell. Biol. 188: 665 – 679. 2010. (* equal contribution).
  • Jaqaman K. and Danuser G., Computational image analysis of cellular dynamics: A case study based on particle tracking. Chapter 15. Live Cell Imaging: A laboratory manual, 2nd ed., Eds Goldman R., Swedlow J. and Spector D., Cold Spring Harbor Laboratory Press. 2010.
  • 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.
  • 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.

Software

Single particle tracking: u-track