• campus:  a to z index
• map
• directory
• calendar

Search:

Katharine S. Ullman

Associate Professor of Oncological Sciences and of Biochemistry

B.A. Northwestern University

Ph.D. Stanford University

Research

References

katie.ullman@hci.utah.edu

Katie Ullman's Lab Page

Katie Ullman's PubMed Literature Search

Research

My lab is interested in the nuclear pore complex, the mitotic roles of nuclear pore proteins, and –more generally– the process of how cellular architecture is remodeled at mitosis. Our long-terms goals are to use this information to better understand how deregulation of these events contributes to both tumor formation and progression and, ultimately, to identify targets that can be used to find new inhibitors of cancerous cell growth.

At interphase, the nucleus and cytoplasm of a eukaryotic cell provide unique environments for specialized processes. The nuclear envelope, formed by two membrane bilayers, forms a barrier between these two main compartments, while at the same time, nuclear pore complexes provide channels through which regulated traffic can take place across this barrier. We are interested in learning how individual components of the pore contribute to selective trafficking.

When a higher eukaryotic cell divides, the nucleus undergoes dramatic morphological remodeling and nuclear and cytoplasmic contents intermix. The nuclear pore complex also disperses at this time. Interestingly, certain components of the nuclear pore complex adopt new roles at mitosis. We discovered that this is the case for the nuclear pore protein Nup153 and we are now pursuing this in more depth in order to gain new insight into events that contribute to nuclear remodeling and mitosis in general.

We take advantage of two complementary experimental systems to dissect the mitotic functions of Nup153 and other proteins of interest. The first is a cell-free system in which material from Xenopus (frog) eggs can be used to not only reconstitute nuclei in vitro, but also to study events triggered by mitotic conditions, such as nuclear envelope breakdown. This system can be readily manipulated to alter the function of particular proteins and study the effect that this has on a process occurring at a certain time. The second approach is to deplete a particular protein from intact cells using RNAi and then follow the impact on cell division using both fixed cell analysis and live imaging techniques. These approaches have revealed that Nup153 contributes to mitosis in novel, unexpected ways. Specifically, we found that Nup153 --as well as a second pore protein, Nup358-- helps to recruit the membrane remodeling complex, COPI, to the nuclear envelope. There is a tandem zinc finger domain within Nup153 that mediates this interaction. We are currently investigating how association between Nup zinc fingers and COPI is regulated and what other molecular players contribute to this process. Our analysis of Nup153 function in mammalian cells has pointed us toward at least one additional role for Nup153 at mitosis, which is one topic of ongoing study.

Panel A. These are oocytes injected with red fluorescent dextran into the nucleus and green fluorescent dextran into the cytoplasm.  The oocyte on the left has an intact nuclear envelope, whereas nuclear envelope breakdown has initiated in the oocyte at right. [Suzanne Elgort]
Panel B.  These are nuclei assembled in a cell-free system and incubated with a red fluorescent protein that is imported through the newly formed nuclear pores (membranes are stained green, DNA is stained blue). [Jin Liu] 
Panel C. This is the nucleus of a cultured human cell, where nuclear pores (red) and COPI membrane remodeling machinery (green) are being monitored as the cell progresses into mitosis. [Amy Prunuske; note: the panels are not shown at the same scale]

References