Cell Biology, Neurobiology & Anatomy

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Alexandra F. Lerch-Gaggl, PhD
Assistant Professor and Director of the Bryant Imaging Core Facility

Department of Cell Biology, Neurobiology & Anatomy
Medical College of Wisconsin
8701 Watertown Plank Road
Milwaukee, WI 53226-0509

Phone: (414) 456-8312
FAX: (414) 456-6517
email: alerch@mcw.edu

Bryant Imaging Core Facility

Education:

MSc, Paris Lodron University Salzburg, Austria, 1996
PhD, Paris Lodron University Salzburg, Austria, 2000
Postdoctoral, Medical College of Wisconsin


Research Area:

Cellular and molecular mechanisms of mammalian development;
Regulatory effects of circadian regulated genes on metabolism

 

 

The formation of embryonic tissues is a complicated, tightly regulated process.  It involves controlled prolific and apoptotic events, which are coordinated by an array of proteins that orchestrate feedback and control mechanisms. In order to form the final, functional structure of the organ in the adult it is necessary that the expression of those proteins is regulated in a timely manner; even minor dysregulations can lead to changes in proliferation and growth behavior resulting in uncontrolled cell proliferation, transformation of the cells, and ultimately to cancer formation.

Our group is studying the protein Pescadillo, which is an essential factor for cell cycle progression and cell proliferation. Its expression is tightly regulated in normal cells. However, we see Pescadillo expression significantly elevated in cells of a variety of human cancers. In a conventional knock out mouse model we have demonstrated that Pescadillo is involved in ribosome biogenesis and that it is essential during early mammalian embryonic development.

Recently, we have performed Yeast Two-Hybrid Screens in order to identify interacting partners for Pescadillo and found that light chain1 of the microtubule-associated protein 1B is one of several interacting partners, that associate with the BRCA1 C-terminus (BRCT) domain of Pescadillo.
 

 

 

  

 

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Another project in our laboratory focuses on the effect of circadian gene regulation on metabolism. There is strong evidence that circadian clocks and metabolism are connected. Endogenous timekeepers or "circadian clocks" in tissues and cells are responsible for rhythmic physiological and behavioral changes corresponding to the daily cycle of day and night - light and dark. Lower organisms as well as humans are guided by these circadian clocks, which in turn control rhythmic biological processes like cell cycle and metabolism. Disturbances in these rhythmic patterns result in deregulation of those fundamental events. According to recent studies the number of people suffering metabolic diseases (i.e. obesity and type-II Diabetes) has significantly increased in the Western hemisphere during the last 20 years as a result of changes in sleep/wake patterns and nutrition.

 

Our working mouse model lacks Nocturnin (Noc-/-), a rhythmically expressed deadenylase, which regulates post-transcriptional mRNA stability and translatability. Noc-/- mice are normal in regard to their circadian rhythmicity and reproduction, but show an obesity-resistant phenotype on a high-fat diet. A detailed preliminary analysis of this phenotype points to a role for Nocturnin in the regulation of lipid metabolism.

 

Selected Publications:
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Lerch-Gaggl, A.F., Sun, K., and Duncan, S.A. (2007). Light chain 1 of microtubule-associated protein 1B can negatively regulate the action of Pes1. J. Biol Chem. 282(15), 11308-16.
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Battle, M. A., Konopka, G., Parviz F., Gaggl, A.L., Yang, C., Sladek, F.M., and Duncan, S.A. (2006). Hepatocyte nuclear factor 4 alpha orchestrates expression of cell adhesion proteins during the epithelial transformation of the developing liver. PNAS 103, 8419-24.
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Liang, H. L., Whelan, H. T., Eells, J.T., Meng, H., Buchmann, E., Lerch-Gaggl, A., and Wong-Riley, M. (2006). Photobiomodulation partially rescues visual neurons from cyanide-induced apoptosis. Neuroscience 139(2), 639-649.
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Lerch-Gaggl, A., Haque, J., Li, J., Ning, G., Traktman, P., and Duncan, S. A. (2002). Pescadillo is essential for nucleolar assembly, ribosome biogenesis, and mammalian cell proliferation. J Biol Chem 277, 45347-45355.

 

 

 

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