Christopher A. Moskaluk, MD, PhD
Molecular analysis of epithelial cancers by gene array. PI for CHTN grant
The focus of the Moskaluk laboratory is the molecular analysis of primary human cancer samples. Global genetic surveys and directed assays of chromosomal content and gene sequences are performed to discover the mutational basis of human cancer. Similarly, gene expression profiling and directed assays of specific gene expression are performed to characterize the gene expression changes that occur during malignant transformation, both to help identify the regulatory pathways involved in tumor pathogenesis, and to discover clinically-useful biomarkers. Techniques that are utilized include Affymetrix GeneChipTM RNA microarray analysis, GeneChipTM SNP analysis, tissue microarrays (TMAs), laser microdissection, RNA amplification, microsatellite PCR, RT-PCR, and immunohistochemistry. Their laboratory is currently focusing on tumors of the lungs and head and neck, but they support investigation into a broad array of human cancers through collaborative efforts. In this laboratory TMAs representing many types of human cancers and non-neoplastic tissue have been constructed to aid in local investigations, and for several NCI-sponsored collaborative consortia groups. As part of their collaborative efforts in national research infrastructure support, high quality frozen tissue samples were collected and provided to the National Cancer Institute's Cancer Genome Anatomy Project (CGAP). These tissues resulted in over 50 CGAP cDNA libraries from which there have been 320,000 sequences deposited in dbEST and approximately 15,000 new human genes discovered. Their own discovery-based investigations have uncovered several genes that have been or are currently being investigated for their functional significance in cancer biology and in clinical utility. These include the up-regulation of a stem cell associated transcription factor (Sox 4) in several human cancer types that appears to confer an anti-apoptotic phenotype. The homeobox transcription factor Cdx-2 was discovered to be up regulated in gastrointestinal carcinomas, and was shown to be an important biomarker in early stages of esophageal tumor progression. They have discovered a novel potentially secreted gene product that is up regulated in squamous carcinoma and are currently investigating its utility as a clinical biomarker in cancer screening.