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Faculty
 Jennifer
S. Tirnauer
Assistant Professor of Medicine
Center for Molecular Medicine
tirnauer@uchc.edu
Areas of Interest:
Microtubules are one of the major organizing structures in the cell.
They give cells their shape, help them move, and serve as tracks for
transport of organelles towards or away from the nucleus. During cell
division, microtubules form the mitotic spindle, responsible for
accurate chromosome segregation. Abnormalities of microtubule
organization can lead to the aberrant mitoses that are a major hallmark
of cancer. Aneuploidy resulting from microtubule defects is also an
important cause of infertility. Several potent drugs that disrupt
microtubules are used clinically -- Taxol is a well known example. These
drugs are extremely effective in blocking mitosis, in cancer cells, as
well as in disorders of cell proliferation such as autoimmune disease
and coronary artery hypertrophy after stent placement. What we need now
is a better understanding of the mechanisms of microtubule disruption in
cancer, and better drugs that are more specific for mitotic
microtubules.
My lab studies microtubules in two ways. First, I am interested in
understanding how microtubules are regulated on a molecular level, and
how microtubule regulatory proteins are controlled in different cell
types. A second goal is to understand how abnormalities in microtubule
regulation lead to errors in cell division, including cancer and
aneuploidy. Specifically, I would like to know when microtubule defects
occur during cancer progression and whether particular microtubule
defects correlate with cancer development, aggressiveness, and response
to treatment. I emphasize live cell imaging as a means to better
understand what is happening in real time. I focus on proteins that bind
to the plus ends of microtubules, both for their potential role as
regulators of microtubule behavior, and as tools to highlight the
dynamic microtubule end. EB1 is an especially interesting protein of
this class, because it is highly conserved, it interacts with the colon
cancer tumor suppressor adenomatous polyposis coli (APC), and it targets
to kinetochores, where the microtubules attach to the chromosomes, in a
unique pattern. I am studying how EB1 interacts with microtubules and
using EB1 as a tool to monitor microtubule polymerization and
organization in different cell types.
Lab Rotation Projects:
MICROTUBULE REGULATION IN NORMAL AND CANCER CELLS
This is a new laboratory studying two related areas - the basic
regulation of microtubules during cell division, and how microtubule
defects contribute to epithelial cancers such as colon cancer. We
welcome students interested in all aspects of cell division and cancer
biology. Specific projects include but are not limited to:
1) We want to understand how microtubules are regulated in
epithelial cells. Using a microtubule binding assay, purify novel
proteins bound to microtubules in polarized epithelial cells. Use high
resolution imaging to localize these proteins during cell polarization
and in cancer vs. normal cells.
2) We have developed an assay for mitotic spindle orientation
in intact tumors and tissues. Compare tumors with normal tissues to
determine the role of tumor suppressors in spindle orientation
3) We have shown a role for the colon cancer tumor suppressor
APC in spindle orientation. Dissect its mechanism in a polarized tissue
culture system using RNAi
4) Develop a project to help understand a basic question in
microtubule regulation. These include mechanisms of dynamic instability,
microtubule dynamics regulation during the cell cycle,
inter-relationships among microtubule plus end binding proteins, and
mechanisms of plus end binding.
Visit the Center For Molecular Medicine webpage:
http://cmm.uchc.edu/index.html
Selected Publications:
Fleming ES, Zajac M, Moschenross DM, Montrose DC, Rosenberg DW, Cowan
AE, and Tirnauer JS. . Planar Spindle Orientation and Asymmetric
Cytokinesis in the Mouse Small Intestine. Journal of Histochemistry and
Cytochemistry, 2007, 55 (11) 1173-80.
Canman, JC, Cameron, LA, Maddox, PS, Straight, A, Tirnauer, JS,
Mitchison, TJ, Fang, G, Kapoor, TM, Salmon, ED. Determining the position
of the cell division plane. Nature, 2003, 424: 1074-1078.
Carvalho P, Tirnauer JS, Pellman D. Surfing on Microtubule Ends.
Trends in Cell Biology, 2003, 13(5): 229-237.
Tirnauer JS, Canman JC, Salmon ED, Mitchison, TJ. EB1 Targets to
Kinetochores with Attached, Polymerizing Microtubules. Molecular Biology
of the Cell, 2002, 13 (12) 4308-4316.
Tirnauer JS, Grego S, Salmon ED, Mitchison TJ. EB1-microtubule
interactions in Xenopus egg extracts: role of EB1 in microtubule
stabilization and mechanisms of targeting to microtubules. Molecular
Biology of the Cell, 2002, 13 (10) 3614-3626.
Tirnauer JS, Bierer BE. EB1 Proteins Regulate Microtubule Dynamics,
Cell Polarity, and Chromosome Stability. The Journal of Cell Biology,
2000; 149(4):761-6.
Lee L, Tirnauer JS, Li J, Schuyler SC, Liu J, Pellman D. Positioning
of the Mitotic Spindle by a Cortical-Microtubule Capture Mechanism.
Science, 2000, 287: 2260-2262. rev 4-08 |
