The homeobox is a highly conserved sequence of 180 base pairs found in most of a group of genes in Drosophila which are known to influence embryonic pattern development. Homeoboxes have also been identified in frogs, mice and humans. A human genomic DNA library will be screened for homeoboxes using Xenopus laevis homeobox probes, and human probes will be prepared. The homeobox containing DNA segments will be mapped to particular chromosomes, and tumors known to carry chromosomal abnormalities in the areas near the homeoboxes will be selected for study. Messenger RNA from tumors and the corresponding normal tissues will be analyzed with Northern blots and by preparing total labeled cDNA from tumors and hybridizing this probe to cloned genes. Southern blots of total genomic DNA will be used to screen for gene amplifications and rearrangements. If the above studies identify differences in homeobox gene expression between tumors and normal tissues, attempts will be made to prepare antibodies to the gene products, and in situ hybridizations as well as fluorescent antibody staining will be used to determine whether changes in homeobox containing gene expression may mark very early cell committment to malignancy, perhaps before malignant changes can be identified by conventional techniques. The above experiments will provide a solid understanding of molecular biological methods, and along with selected courses here at UCLA and reading directed by Dr. DeRobertis, I will be able to acquire the skills and knowledge necessary to pursue my objective of contributing to the understanding of malignancy at the molecular level. I am convinced that only through knowledge at this level will progress in cancer treatment be made. I am very fortunate to be able to work unde the guidance of Dr. DeRobertis who is one of the foremost investigators in the field of homeotic genes and molecular biology.
