Jaspersen Lab

Sue Jaspersen, Ph.D.

Associate Investigator

Professor, Department of Molecular and Integrative Physiology
   The University of Kansas School of Medicine

 

Horizontal Tabs

Profile


As an undergrad at Washington D.C.’s Georgetown University, Sue Jaspersen, Ph.D., was growing weary of writing papers required for her history major. So she took on a challenge that in the end would force a rapid U-turn in her career plans. A student poll had ranked organic chemistry the hardest class on campus, so she decided to enroll in it—just to prove she could succeed.


A thin-section electron micrograph shows the layered SPB structure embedded in the nuclear envelope, which separates the nucleus (N) and cytoplasm (C). The half-bridge (HB) containing a satellite (S) can be seen associated with the SPB. The positions of nuclear (nMTS) and cytoplasmic (cMTs) microtubules are also indicated. Bar, 0.1 μm. (top image.) Cartoon depicting the protein composition of the SPB (bottom image.) 

Image: Jaspersen lab.

“I was majoring in history because I wanted to go to law school and work on Capitol Hill,” says Jaspersen, who hated memorizing the textbook in junior high biology so much she hadn’t even considered a science career. But after acing the organic chemistry class, she changed majors and graduated with a B.S. in chemistry in 1994.

Jaspersen, whose biographical essay to graduate school included the apparently irresistible line, “I’m from Nebraska and I like basketball and cats,” chose the University of California, San Francisco (UCSF), to pursue graduate work in biochemistry. There, as a HHMI pre-doctoral fellow she studied cell cycle regulation in the yeast Saccharomyces cerevisiae in the lab of David Morgan.

Inspired by the multitude of scientific superstars and a vibrant and intellectually stimulating community of students and postdocs working on yeast genetics and cell cycle control at UCSF, Jaspersen became interested in the nuclear structures required for yeast cell division and began to focus on the yeast equivalent of centrosomes, known as the spindle pole body (SPB).

Unlike animal cells—whose nuclear membranes dissolve during cell division—yeast nuclei remain intact, leaving the spindle apparatus that pulls duplicated chromosomes apart inside an enclosed nucleus. For cells to divide, the SPB structure embedded in the nuclear membrane must first duplicate itself and then anchor the spindle at each pole of the nucleus, hence the name.

To characterize this process molecularly, Jaspersen undertook postdoctoral training at the University of Colorado at Boulder with Mark Winey, an expert in centrosome-type structures. There, she distinguished herself as both a Keck Foundation and Helen Hay Whitney postdoctoral fellow, and received a multi-year Leukemia & Lymphoma Society Career Development Award. Between 2000 and 2005, she published studies identifying yeast proteins and cell cycle regulators required for spindle formation, among them a screen published in 2002 in the Journal of Cell Biology (JCB) reporting that SPB duplication required a membrane protein called Mps3.

Ironically, it was at her faculty job talk at Stowers that Jaspersen realized that Mps3 is the yeast orthologue of a family of evolutionarily conserved factors that span the inner nuclear membrane called SUN (for Sad1-UNC-84 homology) proteins. That fact was noted by bioinformaticist Arcady Mushegian who happened to recognize the domain structure. That serendipity resulted in a collaborative paper in the Journal of Cell Biology (JCB) published in 2006.

Jaspersen came to Stowers as an assistant investigator in 2005. “I wanted to be in the Midwest close to my family and work at a place with a great intellectual mix of people,” she says. “We have terrific core facilities and here I collaborate with people who share my interest in nuclear organization but work in multiple systems.”

At Stowers she uses yeast models to study SUN proteins in general and Mps3 in particular. Her 2007 JCB study reported that Mps3 pokes into the nuclear interior and tethers chromosome ends, known as telomeres, indicating that it governs chromosome position within the nucleus and potentially functions in silencing genomic regions adjacent to telomeres. Another 2010 JCB study found that that same Mps3 region also binds to the histone variant H2A.Z, an interaction that targets Mps3 to the inner nuclear membrane.


Jaspersen uses the fungus Ashbya gossypii, which is closely related to Saccharomyces, to study SUN protein function in a multinucleate organism. Nuclei are shown in green.

Image: Jaspersen lab.

She has also begun using the fungus Ashbya gossypii, which is closely related to Saccharomyces, to study SUN protein function in a multinucleate organism. This is important because a subset of inherited laminopathies, or diseases affecting nuclear envelope integrity, is caused by mutations in human SUN proteins. Some of those conditions are marked by muscle wasting accompanied by anomalies in multinucleated cell types such as muscle.

“Nuclear architecture has dramatic effects on gene expression and genomic stability—not just in budding yeast but in all animals,” says Jaspersen. The potential utility of yeast models of human conditions—as well as Jaspersen’s expertise in exploiting them to understand the biology underlying disease—was recognized by the March of Dimes in 2007 when they named her a Basil O’Connor Starter Scholar, an award given for research leading to cures for birth defects.

Cancers also have been linked to disruption in normal nuclear organization or mutations in genes encoding nuclear envelope proteins. “My favorite model is that chromosomal translocations seen in leukemia are favored because those chromosomes are in proximity to each other—in other words that nuclear organization contributes to cancer,” she says. “We have developed the molecular tools to test that in yeast.” 

Since abruptly changing direction during her college days, Jaspersen has been on a straight and successful trajectory that took her from the SPB to the role of the nuclear membrane in human cancer. In 2010, Jaspersen was awarded an American Cancer Society Research Scholar Award to study the role of SUN proteins in cancer.