There are many parallels between mammary epithelial cells during pregnancy and in breast cancer. In both instances cells are undergoing proliferation, and differentiation is suppressed. In addition, mammary epithelial cells show invasive properties under both conditions. LMO-4, one of the genes we are investigating, is upregulated in mammary epithelial cells both during pregnancy and in breast cancer cells.

Our laboratory welcomes students at various stages of training. We are enthusiastic about training graduate students within the Molecular Biology, Genetics and Biochemistry graduate program, to which our laboratory belongs. Graduate students whose main interests fall within the Cancer Biology, Developmental Biology and Genetics, and Mechanisms of Gene Expression tracks should be able to find excellent training opportunities within the laboratory.

We have limited number of spots for undergraduate students and offer 190 and 199 courses for undergraduates interested in pursuing independent study. The optimal time for undergraduate students to inquire about projects is probably at the end of the first or the start of the second year. We are especially encourage students who plan future careers in scientific research to contact our laboratory.

Students in our laboratory are encouraged to use multidisciplinary approaches to address the scientific questions we are interested in. In part, our laboratory draws strength by working with excellent core facilities at UCI, including the transgenic core and the DNA microarray core. Currently, the laboratory employs a variety of approaches to reach our research objectives:

A schematic model for possible oncogenic effects of LMO-4. In epithelial cells, such as in the epidermis and the mammary gland, LMO-4 interacts with the transcriptional co-factor called Clim. The LMO-4/Clim complex then associates with DNA-binding proteins thereby activating the expression of genes that promote tumorigenic features of epithelial cells. We are using a variety of approaches to test this model.

1. Molecular Biology techniques, such as cDNA cloning, including protein-protein interaction cloning using the yeast two-hybrid system, as well as analyses of gene expression with a variety of techniques, including quantitative PCR, RNAse protection assays and in situ hybridization.
2. Biochemistry techniques to study protein-protein interactions and protein-DNA interactions as well as regulation of gene expression within cells. We are also using tagged proteins in combination with mass spectrometry to identify LMO-4- and Clim-interacting proteins.
3. Cell Biology techniques to study the effects of mutations on the behavior of epithelial cells.
4. Mouse Genetics to study the role of genes within the context of whole mammalian organisms, using standard transgenic and knockout mice.
5. Histology techniques to study pathology in transgenic and knockout mice and immunohistochemistry to study protein expression within tissues.
6. Genomics and Bioinformatics approaches to study global changes in gene expression during development, in disease and as a result of mutations, using Affymetrix microarrays.

Two types of epithelial cancer: A, basal cell carcinoma of the skin, and B, ductal carcinoma of the breast. Arrows point to cancer foci. Ep refers to epidermis.

Our laboratory meets once weekly for data discussion where members of the laboratory present their work. In addition, we meet once weekly for a journal club where members of the laboratory alternate to present and discuss papers of interest to our research. In addition, laboratory members are encouraged to attend seminars, including the weekly cancer journal club held at Sprague hall.