Vaughan Lee, Ph.D.
My ultimate research goal is to understand the regulatory mechanisms controlling specific aspects of ovarian development and function. I am specifically interested in differentiation and development of granulosa cells in growing follicles, their regulatory mechanisms, and how these may relate to the development of ovarian cancer. A current project in my laboratory is investigating the regulation of connexin 43 in granulosa cells and its involvement in tumorigenesis in ovarian cells. Like other types of cancers, some ovarian cancers exhibit the loss of normal connexin expression as part of their tumorigenic process. Connexins, proteins that form gap junction channels which facilitate intercellular communication, are well-documented tumor suppressors. Restoring connexin expression in cancer cells inhibits tumor growth by preventing uncontrolled proliferation and re-establishing of normal density-dependent growth. In ovarian granulosa cells, connexin 43 expression and proliferation are simultaneously stimulated to achieve normal growth in developing follicles. A model for normal follicle growth was developed in which epidermal growth factor stimulates connexin 43 expression and proliferation in cultured rabbit granulosa cells. This model will be utilized to determine the molecular mechanism coupling connexin 43 expression and proliferation in granulosa cells, and to show that disruption of this regulation can lead to uncontrolled proliferation. Disruption of this regulation could be one mechanism by which granulosa cell cancers, as well as tumors from other cell types, develop. Components of this regulatory mechanism could be future targets for biological therapy and chemoprevention of multiple types of cancers.
A second research project utilizes pigs, an agriculturally important species, which have a prepubertal pattern of ovarian development similar to rabbits. My laboratory group has reported that increased expression of connexin 43 is associated with growth of early preantral follicles in pigs as in rabbits. Furthermore, epidermal growth factor enhances connexin 43 expression in early preantral pig follicles and that estrogen receptor mRNA is expressed in these immature pig follicles. The hypothesis is that the epidermal growth factor and estrogen signaling pathways interact to modulate early folliculogenesis through altering connexin 43 expression. Results of this work will not only improve our knowledge about regulation of early follicular development but will allow us to design techniques to improve reproductive efficiency on commercial pork farms.
The knowledge gained from these interrelated projects will lead to a better understanding of normal molecular processes involved in regulation of development and function in mammalian ovaries. This basic knowledge may help develop new approaches to manipulate ovarian function and manage ovarian cancer.
I have taught Medical Gross Anatomy for over thirteen years in several different institutions and have been Director of Medical Gross Anatomy at TTUHSC since 2004. In 2004-2005 I served on the TTUHSC Curriculum Redesign Committee and as Chair of Foundations of Medical Sciences Block Redesign Team. In 2005 I served as Block 1 Leader in the First Year Medical Curriculum: Foundations of Medical Sciences Block. Since 2003 I have been director of the Surgical Anatomy Elective and the 4th Year Advanced Anatomy Elective.
- Kennedy, K.L., Floyd, A.A., Clarkson, A.M., and Lee, V.H. 2003. Epidermal Growth Factor Regulation of Connexin 43 in Cultured Granulosa Cells from Preantral Rabbit Follicles. Mol Reprod Devel 64:61-69.
- Bolamba, D., Floyd, A.A., McGlone, J.J., and Lee, V.H. 2002. Epidermal Growth Factor Enhances Expression of Connexin 43 Protein in Cultured Porcine Ovarian Explants and Preantral Follicles. Biol. Reprod. 67:154-160.
- Melton, C.M., Patino, R., Zaunbrecher, G., Rendon, A., Whisnant, C.S. and Lee, V.H. 2001. Expression of connexin 43 mRNA in developing follicles of prepubertal porcine ovaries. Comparative Biochemistry and Physiology Part B 130:43-55.
- Xiaotian Chang, X., Pati�o, R., Yoshizaki, G., Thomas, P., and Lee, V.H. 2000. Hormonal Regulation and Cellular Distribution of Connexin 32.2 and Connexin 32.7 RNAs in the Ovary of Atlantic Croaker. General & Comparative Endocrinology 120:146-156.
- Lee, V.H. 2000. Expression of Rabbit Zona Pellucida 1 (ZP1) mRNA during Early Follicular Development. Biol. Reprod. 63:401-408.
- Rendon, A., Hewetson, A., Chilton, B.S. and Lee, V.H. 2000. Expression of RUSH transcription factors in developing and adult rabbit gonads. Biol. Reprod. 63:156-164.
- Lee, V.H. and McGlone, J.J. 1998. Accelerating Ovarian Maturation. National Hog Farmer 43:29-30.