Jennifer
S. Tirnauer, M.D.
Investigator, Center for Molecular Mediciine
Assistant Professor of Medicine
Biographical Sketch
Email: tirnauer@uchc.edu
Phone: 860-679-3728
Fax: 860-679-7639
Research
Interests
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.