Dr. Nam-Sung Moon
Associate Professor

Current Research

1. Analysis of the genetic interaction between rbf1 and the Drosophila homologues of human cancer genes.
While RB inactivation is believed to be an initiating event, cancer cells must acquire additional genetic alterations to fully transform into cancer cells. To identify factors that can cooperate with RB mutations, we are investigating combinatorial effects of mutating the Drosophila ortholog of RB, rbf1, and other tumor suppressor genes in flies. For example, we reported that mutations in the Tuberose Sclerosis Complex tumor suppressor genes promote ectopic S-phase entry and cell death in rbf1 mutant cells during Drosophila eye development (Hsieh et al. PLoS genetics 2010).

tsc1 and rbf1 mutations cooperate to promote S-phase entry during eye development. tsc1 mutant clones are generated in wild type and rbf1 mutant eye discs. Wild type clones are marked with GFP (green) and the lack of GFP indicates tsc1 mutant clones. The position of the Morphogenetic Furrow (MF), where cells normally arrest in G1, is indicated by a yellow arrow. S-phase cells are visualized by anti-BrdU antibody (red). The image of higher magnification of the indicated area is shown. Note that the cells with both tsc1 and rbf1 mutations enter S-phase at the MF, demonstrating the they can overcome developmentally regulated G1 arrest.

2. Identification of factors that synergize with rbf1 loss-of–function
One of the advantages of working with genetic model organisms such as Drosophila melanogaster is that it is possible to conduct unbiased genetic screens. Previously, a genetic screen was conducted to identify factors that can specifically cooperate with rbf1 mutations to affect Drosophila eye development. A gene identified from this genetic screen is Extra-Machrochaetae (EMC) (Popova et al. J. Cell Sci. 2011). The mammalian ortholog of EMC was previously shown to be important for the developmental defects obverted in RB knockout mice. Our work demonstrated that an unbiased genetic screen in Drosophila could identify factors that are important for the mammlian RB tumor suppressor gene. My lab is currently investigating other factors identified from this genetic screen.

The d09015 allele, which can induce expression of EMC, differently affects the eye development of wild-type and rbf1 mutant flies. (A) Pupal eye discs of control and rbf1 mutant flies by themselves or crossed with the d09015 allele were stained with anti-ELAV (white) and anti-Cut (red) antibodies. ELAV is a marker for photoreceptors and Cut is a marker for cone cells. Note that the abnormalities in the cone cell staining pattern in the rbf1 mutant flies that overexpress EMC (d09015) are often associated with irregular ELAV staining patterns (yellow Arrows). (B) Pupal eye discs of indicated genotypes were stained with anti-ELAV (blue) and anti-Chaoptin (red) antibodies. Chaoptin is a glycoprotein specifically expressed in photoreceptors and localized to the membrane. Note the irregular pattern of photoreceptors in rbf1 mutant flies crossed to d09015.