Alexander E. Kelly, Ph.D.
Alexander E. Kelly, Ph.D.
Investigator
Head, Chromosome Dynamics and Genome Stability Section

Center for Cancer Research
National Cancer Institute

Building 37, Room 6118
Bethesda, MD 20892-4260
301-402-1562

The Kelly lab uses a combination of biochemistry, human cell culture and transcriptionally silent Xenopus egg extracts to investigate 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.

Areas of Expertise
1) mitosis 2) chromosome biology 3) histone modifications 4) Aurora B kinase 5) kinetochore signaling 6) Xenopus egg extracts

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.

Scientific Focus Areas:
Cell Biology, Chromosome Biology, Molecular Biology and Biochemistry, Structural Biology
Selected Key Publications
  1. Du J, Kelly AE, Funabiki H, Patel DJ.
    Structure. 20: 185-95, 2012. [ Journal Article ]
  2. Kelly AE, Ghenoiu C, Xue JZ, Zierhut C, Kimura H, Funabiki H.
    Science. 330: 235-9, 2010. [ Journal Article ]
  3. Kelly AE, Funabiki H.
    Curr. Opin. Cell Biol. 21: 51-8, 2009. [ Journal Article ]
  4. Kelly AE, Sampath SC, Maniar TA, Woo EM, Chait BT, Funabiki H.
    Dev. Cell. 12: 31-43, 2007. [ Journal Article ]
  5. Kelly AE, Kranitz H, Dötsch V, Mullins RD.
    J. Biol. Chem. 281: 10589-97, 2006. [ Journal Article ]

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.

Name Position
Mary Kate Bonner Ph.D. Postdoctoral Fellow (CRTA)
Julian Haase Research Biologist (Contr.)
Hyunmi Kim Halas Ph.D. Postdoctoral Fellow (CRTA)
Justin Zhang Postbaccalaureate Fellow

Summary

The Kelly lab uses a combination of biochemistry, human cell culture and transcriptionally silent Xenopus egg extracts to investigate 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.

Areas of Expertise
1) mitosis 2) chromosome biology 3) histone modifications 4) Aurora B kinase 5) kinetochore signaling 6) Xenopus egg extracts

Research

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.

Scientific Focus Areas:
Cell Biology, Chromosome Biology, Molecular Biology and Biochemistry, Structural Biology

Publications

Selected Key Publications
  1. Du J, Kelly AE, Funabiki H, Patel DJ.
    Structure. 20: 185-95, 2012. [ Journal Article ]
  2. Kelly AE, Ghenoiu C, Xue JZ, Zierhut C, Kimura H, Funabiki H.
    Science. 330: 235-9, 2010. [ Journal Article ]
  3. Kelly AE, Funabiki H.
    Curr. Opin. Cell Biol. 21: 51-8, 2009. [ Journal Article ]
  4. Kelly AE, Sampath SC, Maniar TA, Woo EM, Chait BT, Funabiki H.
    Dev. Cell. 12: 31-43, 2007. [ Journal Article ]
  5. Kelly AE, Kranitz H, Dötsch V, Mullins RD.
    J. Biol. Chem. 281: 10589-97, 2006. [ Journal Article ]

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.

Team

Name Position
Mary Kate Bonner Ph.D. Postdoctoral Fellow (CRTA)
Julian Haase Research Biologist (Contr.)
Hyunmi Kim Halas Ph.D. Postdoctoral Fellow (CRTA)
Justin Zhang Postbaccalaureate Fellow