Sue Biggins

Appointments and Affiliations

 
 
Fred Hutchinson Cancer Research Center
Basic Sciences Division
Member, Appointed: 2010
University of Washington
School of Medicine
Biochemistry
Affiliate Professor, Appointed: 2011
Professional Headshot of Sue  Biggins

Mailing Address

1100 Fairview Ave. N.
Mailstop A2-168
P.O. Box 19024
Seattle, Washington 98109
United States

Contact

Phone: (206) 667-1351
Fax: (206) 667-6526
http://labs.fhcrc.org/biggins/index.html

Degrees

Ph.D., Princeton University, Molecular Biology, 1995.
B.S., Stanford University, Biology, 1990.

Research Interests

Regulation of chromosome segregation.

How do cells faithfully inherit a complete set of chromosomes during every cell division? My laboratory is focused on elucidating the mechanisms that govern chromosome segregation. Because aneuploidy is a hallmark of all cancers and many birth defects, studies on chromosome segregation are critical to understanding how cells maintain genomic stability and prevent disease. Chromosomes segregate using their kinetochores, the specialized protein structures that are assembled on centromeric DNA sequences and attach to dynamic spindle microtubules. Sister kinetochores must make bioriented attachments to microtubules from opposite poles. Defects in making bioriented kinetochore attachments are detected by the spindle checkpoint that halts the cell cycle until the errors are corrected. My lab is studying many key questions about chromosome segregation, including how kinetochores assemble, how kinetochores make bioriented microtubule attachments, and how the spindle checkpoint detects and corrects defects in these processes.

Kinetochores contain a specialized centromeric chromatin structure containing a conserved centromeric histone H3 variant (CenH3) that appears to be the epigenetic mark that specifies the site of kinetochore assembly. We previously discovered that CenH3 is regulated by ubiquitin-mediated proteolysis to restrict CenH3 localization to kinetochores. We have recently identified a ubiquitin ligase that degrades CenH3 that mislocalizes to euchromatin and are currently studying its regulation. We also have a number of projects studying histone modifications that are important for various aspects of centromeric function.

We also study the regulation of kinetochore biorientation and the spindle checkpoint. A key regulator of chromosome segregation in all eukaryotes is the Ipl1/Aurora protein kinase. Because the Aurora kinases are oncogenes, studies on the budding yeast Ipl1 protein are critical to understanding both chromosome segregation and the maintenance of genomic stability. Current projects in the lab are directed at identifying key substrates for Ipl1 and Glc7 as well as understanding the precise temporal and spatial regulation of the enzymes.

Recently, we reconstituted kinetochore-microtubule attachments in vitro using purified kinetochore particles. We are collaborating with Chip Asbury's lab at UW to perform biophysical experiments to further understand the mechanisms that regulate attachments. We are also collaborating with Tamir Gonen to elucidate structural details about kinetochores and their mode of attachment to microtubules. Finally, we are using this assay to identifiy novel post-translational modifications on kinetochores and to reconstitute the spindle checkpoint in vitro. Taken together, these studies should continue to elucidate new details about the mechanisms of chromosome segregation and thus aid in understanding the generation of aneuploidy and disease progression.

Memberships

American Society for Cell Biology
Genetics Society of America

Honors and Awards

2005-2010, LLS Scholar, LLS
2003-2006, Beckman Young Investigator, Beckman Foundation
2000-2003, Sidney Kimmel Scholar, Sidney Kimmel
1998-2000, ACS Senior Postdoctoral Fellow, ACS
1995-1998, Jane Coffin Childs Postdoctoral Fellow, JCC

Previous Positions

2005-2010, Associate Member, Fred Hutchinson Cancer Research Center, Basic Sciences Division, Division of Basic Sciences
2000-2004, Assistant Member, Fred Hutchinson Cancer Research Center, Basic Sciences Division, Division of Basic Sciences

Funding

  • NIH: Regulation of Centromeric Chromatin, 2007 to 2011.
  • Beckman Foundation: Beckman Award, 2003 to 2006.
  • NIH: Regulation of Chromosome Segregation, 2001 to 2015.
  • Sidney Kimmel Foundation: Kimmel Award, 2000 to 2003.

Recent Publications

2018
2017
2016
2015
2014
2013
2012
2010

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