The intent of this proposal is to educate and train a medical graduate for a career in research. We have therefore designed a formal academic program and research project for Dr. Melissa Conrad which will provide her with the background and hands-on experience for developing into an independent research scientist. Her academic course work has been selected with the advice of 5 established professors in each of the departments in which she will train, and her research project will be performed in an established research laboratory under the direct supervision of Dr. Richard Schlegel. The proposed research project was chosen to integrate well into the main interests of Dr. Schlegel's laboratory to insure that Dr. Conrad would receive optimal training and interaction with the other postdoctoral researchers in the laboratory. finally, the research project chosen represents a state-of-the-art approach to studying a viral oncogene and its biological and biochemical activities. This project will therefore provide Dr. Conrad with training in the most current molecular, biochemical, and cellular techniques. The proposed research project will encompass both Phase 1 and Phase 2 of Dr. Conrad's training and consists of expressing and characterizing the E5 proteins of the human papillomaviruses. These viruses are sexually transmitted, infect the human genital tract, and initiate pathological lesions at these sites as well as contribute to the development of neoplasia, both benign and malignant. The HPV E5 proteins, whose counterpart in BPV-1 is a well-defined oncoprotein, are poorly characterized for function and biochemical activity. Interestingly, the HPV E5 proteins sort into two homologous groups: (1) those encoded by HPV- 6 and HPV-11 (which are associated with non-dysplastic epithelial lesions and benign genital tumors), and (2) those encoded by HPV-16 and HPV-18 (which are associated with dysplastic epithelial lesions and malignant genital tumors). The intent of the research proposal is to express the above HPV E5 proteins in a well-established vector which has been used successfully for the BPV-1 E5 protein. The HPV E5's will then be characterized biologically to determine whether they exhibit transforming and/or mitogenic activities. The HPV E5's will also be examined biochemically and compared with the E5 of BPV-1. After having established the biological and biochemical properties of the HPV E5's, Dr. Conrad will enter Phase 2 of her research training and undertake an extensive mutagenic analysis of the HPV E5's in order to define their functional domains. These studies will be important for understanding the different biological sequelae consequent to infection by the various types of HPV.
| Stoppler, M C; Straight, S W; Tsao, G et al. (1996) The E5 gene of HPV-16 enhances keratinocyte immortalization by full-length DNA. Virology 223:251-4 |
| Stoppler, M C; Ching, K; Stoppler, H et al. (1996) Natural variants of the human papillomavirus type 16 E6 protein differ in their abilities to alter keratinocyte differentiation and to induce p53 degradation. J Virol 70:6987-93 |
| Conrad, M; Goldstein, D; Andresson, T et al. (1994) The E5 protein of HPV-6, but not HPV-16, associates efficiently with cellular growth factor receptors. Virology 200:796-800 |
| Conrad, M; Bubb, V J; Schlegel, R (1993) The human papillomavirus type 6 and 16 E5 proteins are membrane-associated proteins which associate with the 16-kilodalton pore-forming protein. J Virol 67:6170-8 |
