I, Concepcion R. Diaz-Arrastia, am a gynecologic oncologist interested in basic science research regarding cervical carcinoma, the second most common cause of cancer death in women worldwide. Completing the University of Texas Medical Branch (UTMB) Women's Reproductive Health Research mentored career development program (K-12) has allowed me to learn and apply basic molecular biology techniques and design a research plan. I have optimized techniques for analyzing cervical carcinoma specimens at the RNA and protein levels. This K22 career transition award will allow me to further develop my current work for competitive R01 awards, with the long-term goal of understanding the mechanisms involved in cervical cancer invasion and metastasis. During this award period, my ability to analyze the complex microarray and proteomic data will become even more sophisticated. UTMB offers an excellent environment to support this work, at both the academic and clinical levels. The university is a leader in bioinformatics, with core facilities in microarray analysis as well as proteomics. I have a close working relationship with scientists in the Department of Human Biological Chemistry & Genetics, where these facilities are located. As the only public health care facility in Texas with a gynecologic oncology service, UTMB has a wealth of clinical material in cervical carcinoma. The purpose of the proposed study is to develop a genomic and proteomic profile of early carcinoma of the cervix.
We aim to identify the genes involved in the development of invasion and metastasis at the RNA level and validate them at the protein level in order to elucidate cervical carcinogenesis at the molecular level. RNA and total protein is extracted from cervical carcinoma tissue that has varying histologic prognostic factors. A high-density genomic analysis is performed using the Affymetrix human gene chip. Based on our preliminary microarray data, several members of the matrix metalloproteases subfamily differentiate superficially from deeply invading cervical carcinomas. These putative biomarkers of early invasive carcinoma are validated by immunoblotting, and their identity will be confirmed by mass spectrometry. The resulting molecular signature is correlated to the biologic behavior of the tumors. I propose to identify a genomic and proteomic signature of cervical cancer that will predict the aggressive behavior of the tumor and function clinically to develop molecular-based treatment plans.
| Botting, Shaleen K; Trzeciakowski, Jerome P; Benoit, Michelle F et al. (2009) Sample entropy analysis of cervical neoplasia gene-expression signatures. BMC Bioinformatics 10:66 |
