Alexander E. Kelly, Ph.D.

Investigator

Laboratory of Biochemistry and Molecular Biology

NCI/CCR

Building 37, Room 6118
Bethesda, MD 20892-4260

(240) 760-7557

alexander.kelly@nih.gov

Research Topics

The Kelly lab investigates the mechanisms eukaryotic cells use to ensure the faithful segregation of chromosomes, with a focus on the roles of post-translational modification of chromatin and kinetochore components during mitosis. A major research interest is the mechanism by which mitotic proteins 'sense' and correct improper microtubule-kinetochore attachments. These errors can give rise to aneuploidy and genome instability, both hallmarks of cancer cells. In addition, the lab studies the roles of mitotic histone modification and modifying enzymes in centromere formation and genome stability. Efforts are underway to identify new mitotic modifications of centromere and kinetochore components and the enzymes that place and remove them. The lab uses a combination of biochemistry, human cell culture and transcriptionally silent Xenopus egg extracts to understand how chemical signals at the kinetochore and centromere ensure high-fidelity chromosome segregation.

Biography

Dr. Kelly received a Ph.D. in Biophysics from the University of California, San Francisco in 2005. Working in the laboratories of Volker Dotsch and Dyche Mullins, he developed structural and biochemical techniques to dissect the molecular mechanisms of actin polymerization. As a postdoctoral fellow in the laboratory of Hironori Funabiki at the Rockefeller University, his work focused on the mechanism of activation of Aurora B kinase, a major cancer therapy target that orchestrates many aspects of mitosis. These studies led to the discovery of the non-transcriptional role of histone modification in the spatial control of chromosome segregation. He joined the Laboratory of Biochemistry & Molecular Biology in 2012.

Selected Publications

  1. Du J, Kelly AE, Funabiki H, Patel DJ. Structural basis for recognition of H3T3ph and Smac/DIABLO N-terminal peptides by human Survivin. Structure. 2012;20(1):185-95.

  2. Kelly AE, Sampath SC, Maniar TA, Woo EM, Chait BT, Funabiki H. Chromosomal enrichment and activation of the aurora B pathway are coupled to spatially regulate spindle assembly. Dev Cell. 2007;12(1):31-43.

  3. Kelly AE, Ghenoiu C, Xue JZ, Zierhut C, Kimura H, Funabiki H. Survivin reads phosphorylated histone H3 threonine 3 to activate the mitotic kinase Aurora B. Science. 2010;330(6001):235-9.

  4. Kelly AE, Kranitz H, Dötsch V, Mullins RD. Actin binding to the central domain of WASP/Scar proteins plays a critical role in the activation of the Arp2/3 complex. J Biol Chem. 2006;281(15):10589-97.

  5. Kelly AE, Funabiki H. Correcting aberrant kinetochore microtubule attachments: an Aurora B-centric view. Curr Opin Cell Biol. 2009;21(1):51-8.


This page was last updated on September 28th, 2017