Understanding the molecular regulatory mechanisms of early folliculogenesis during ovarian development Teaching Interest:
Medical Education (Area of excellence, 2003 - present): Developing dissection guides and videos for students to use in peer-based teaching and creating Web-based tools that promote independent learning for cross-sectional anatomy and radiographic imaging. With this approach, knowledge and life-long learning skills of medical students can be enhanced (45% scholarly activity).
My primary goal in medical education is to design and coordinate programs to effectively and efficiently teach clinically relevant Anatomy to medical students. Certain components of Anatomy can be most effectively taught to medical students by engaging them in self-directed learning exercises with the appropriate supporting resources (customized guides and demonstration videos). Much of my recent effort focused on developing dissection guides and videos for students to use in peer-based teaching exercises and creating Web-based imaging tools that allow students to independently learn cross-sectional anatomy and basic radiographic imaging. These methods are more effective because active learning through teaching others has a higher long-term retention rate (80%) as compared to more traditional passive presentation formats (5%). Additionally, these learning formats help the students begin to develop a basis for life long learning skills. These educational methods increase efficiency of medical Anatomy programs by reducing the individual teaching time demanded of Basic Science faculty, thus enhancing time for research. As these anatomy programs become more efficient, the anticipated decline in experienced anatomist will have less of an impact on medical education in Anatomy programs utilizing more self-directed activities. With this systematic approach to improving anatomy teaching programs, knowledge and life-long learning skills of medical students can be enhanced in all stages of their medical education.
Medical Education Innovations (Scholarly activity in Medical Education)
1. Supervision and development of self-directed dissection guide for Medical Gross Anatomy.
2. Developed and expanded use of Web-based videos for dissection guide supplement.
3. *Established and expanded Student Teaching Students (STS) initiative for self-directed learning in Gross Lab Sessions.
4. *Supervision and development of Web-based study materials for cross-sectional and radiographic images.
5. Clinically Oriented Anatomy Block 1 leader: developed and implemented integrated curriculum for introduction of clinically oriented anatomy and clinical examination skills.
6. *Developed and promoted plan to utilize Web based videos to supplement embryology instruction in Clinically Oriented Anatomy.
7. Expanded Surgical Anatomy Elective for 1st year Medical students.
8. Expanded 4th year Surgical Anatomy Elective.
9. Directed Anatomy Prelabs for Junior teaching faculty.
10. Organized prosection material preparation for Gross Lab.
11. Developed and expanded use of AV technologies in Gross Lab experience.
12. Developed and supervised Anatomy Peer Tutoring Program (Second Year Students).
13. Support for the annual Surgery Club Suture Clinic
14. Developed pilot proposal for use of computers and our computer based resources for teaching in the anatomy lab. Waiting funding by SOM to implement in curriculum.
*Items presented at National Meetings.
Research Interests:
BS Research: (45% scholar activity) We have established a temporal correlation of altered mitochondrial connexin 43 proteins with apoptosis in MA10 Leydig cells and two ovarian cancer cell lines. We are developing this new and novel model into a project that will be competitive for national grant moneys.
Mitochondrial Connexin 43 and its Role in Apoptosis: Chemotherapy relies on the release of factors from mitochondria which destroy cancer cells; a process known as apoptosis. Unfortunately, malignant cells are often able to avoid destruction by blocking apoptosis. Our recent observations that the channel protein, connexin 43, disappears from mitochondria shortly after exposure to the cancer drug, etoposide, raises the intriguing question of whether this channel is involved in regulating apoptosis. Currently, we have detected mitochondrial connexin 43 in MA10 Leydig cells, KK1 granulosa cells, adrenal cells, Sertoli cells, and ovarian cancer cell lines, OVCAR3 and SK-Ov-3. Our next step is measuring etoposide induced apoptosis while blocking the channel via two methods; first by siRNA inhibition of connexin 43 synthesis and second with the pharmacological blocker, beta glycyrrytenic acid. If apoptosis is increased by inhibition of mitochondrial connexin 43 channels, it could provide valuable insights into improving cancer chemotherapy. Molecular regulation of ovarian development and function
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.
Collaborative Research Activities:
1. Developing EM techniques for visualizing molecules associated with mitochondrial function, Charlie Lynch and Drs. Matt Dyson and Doug Stocco.
2. Working with Dr. Vidic and group in France: Topographic TEM localization of Cx43 in mitochondrial inner membrane.
3. Dr. Min Kang: Working with Dr. Kang to characterize changes in mitochondrial Cx43 in cell apoptosis and conducting a survey of Cancer cell lines for Mitochondrial Cx43.
4. Promoting independent study skills in Anatomy using supplemental Embryology lectures on web-based videos. Drs. Elmus Beale and Harry Weitlauf.
5. Pheromone activation of porcine olfactory bulb, vomeronasal organ, and accessory olfactory bulb in prepubertal gilts. Dr. John J. McGlone, Dept. of Animal Science and Food Technology, Texas Tech University.
6. Expression and regulation of galectin-3 and cubilin in the utero-placental complex during gestation with Dr. Harry Weitlauf, Dept. of Cell Biology and Biochemistry, Texas Tech University Health Sciences Center. These studies were designed to establish the spatio-temporal patterns of galectin-3 and cubilin in both fetal and maternal tissues and determine whether it is differentially regulated.
7. Increasing litter size in gilts through acceleration of prepubertal ovarian development. Dr. John J. McGlone, Dept. of Animal Science and Food Technology, Texas Tech University.
4. Expression of FSH receptors in rat testis with Dr. Jim Hutson, Dept. of Cell Biology and Biochemistry, Texas Tech University Health Sciences Center. These studies were designed to determine whether FSH receptors are expressed on other cell types in the rat testis in addition to Sertoli cells.
5. Localization of SKM-2 membrane channel mRNA in brain with Dr. Laurel Donahue, Dept. of Cell Biology and Biochemistry, Texas Tech University Health Sciences Center. This channel is expressed in heart and brain tissues and a mutation of this protein is potentially linked with cardiac arrhythmias and epileptic seizures in some patients.
6. Characterization of connexin 43 expression during folliculogenesis in horse ovaries with Dr. Hiedi Brady, Dept. of Animal Science and Food Technology, Texas Tech University. Development of gap junctions containing connexin 43 is a crucial step in maturation and function of ovarian follicles. These studies will determine when connexin 43 expression is initiated during early stages of folliculogenesis and how it may be regulated.
7. Expression of relaxin-like proteins in the placenta and uterine epithelium in pregnant rabbits with Dr. Phillip Fields at the University of South Alabama College of Medicine, Dept. of Structural and Cellular Biology.
8. Expression of RUSH and RFBP in rabbit gonads with Dr. Beverly S. Chilton, Dept. of Cell Biology and Biochemistry, Texas Tech University Health Sciences Center. These studies determined the pattern of expression of RUSH and RFBP in developing gonads (granulosa cells and Sertoli cells). The pattern of expression of RUSH and RFBP in these cell types is indicative of mechanisms of hormonal regulation of gene transcription.
9. Role of connexin gap junctional communication in oocyte maturation and ovulation with Dr. Reynaldo Patiño, Texas Coop Fish/Wildlife Res., Texas Tech University, Texas Tech University.
10. Reproductive efficiency in Feral Hogs. Duane R. Lucia, Texas Parks & Wildlife.
11. Analysis of ecdysone receptor changes in silkworms, Dr. S. Sridhara, Dept. of Cell Biology and Biochemistry, Texas Tech University Health Sciences Center. We are investigating the role of ecdysone in regulating ovarian maturation in silkworms.
12. Expression of androgen binding protein in salivary glands of deer mice as a marker for environmental toxicants, Dr. Ernest Smith, TTU Institute for Environmental and Human Health and Dr. Carl J. Phillips, Dept. of Biological Sciences, Texas Tech University.
Medical Gross Anatomy, Ovarian Develpment and Function, Reproductive Biology
