The Division of Reproductive and Developmental Biology Department of Pediatrics at Vanderbilt University Medical Center VU Help Search Vanderbilt Medical Center Sanjoy K. Das, Ph.D Bibhash C. Paria, Ph.D S. K. Dey, Ph.D
The Division of Reproductive and Developmental Biology



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R.B. Training Grant




Reproductive Biology Training Program (RBTP)
"Training for the 21st Century"
Vanderbilt University Medical Center

Scientific Rationale for our Program

The primary objective of the training program in reproductive biology (RBTP) is to continue offering predoctoral and postdoctoral training to individuals who demonstrate potential for developing into independent investigators in the field of reproductive biology. The will be accomplished by including multidisciplinary interests to expand the horizon of training for students and better prepare their career paths in the 21st century. This will present them with opportunities to make significant scientific contribution to reproductive and related developmental biology. There is much excitement in the field recently due to scientific innovations, opportunities and advances in biomedical sciences and evolving technologies. Students will be educated in an environment where specific biological problems are addressed using contemporary knowledge in developmental biology, physiological genomics, proteomics, signal transduction, molecular and cellular biology. The present environment at Vanderbilt in the field of Reproductive Biology is highly conducive to such training, due to a broad based interactive group of eighteen investigators spanning several departments and thematic areas. The recent establishment of genomics, proteomics, lipidomics and imaging centers on the campus with state-of the art facilities will further build on the opportunities to students. Training will occur with major emphasis in:

1) Sperm functions and fertilization

2) Uterine biology

3) Preimplantation embryo development and implantation biology

4) Genetic regulation of gonadotropin secretion

These areas of research training are led by some of the top scientists in the field; preceptors who are experts in developmental biology, signal transductions, genomics and proteomics just to name a few. (link to list of preceptors and THEIR LINKS/creds here)

Sperm functions and fertilization. Dr. Greenstein's current work, using C-elegans as a model system, focuses on further defining a sperm-sensing control mechanism in oocytes. When sperm are unavailable this mechanism inhibits oocyte maturation, MAPK activation, and ovulation. Drs. Matusik and Orgebin-Crists' laboratories study sperm maturation in the mouse epididymis. Their work currently focuses on the consequence of interactions between the spermatozoa and the epididymal microenvironment on sperm maturation. Dr. Olson's laboratory has been engaged in studying sperm acrosome structural modification in the epididymis and sperm motility in rodents. More recently he has launched a joint collaboration with the laboratory of Dr. Burk, who is an authority in nutrition and oxidative stress research, to study the role of selonoprotein in sperm functions at the genetic and molecular level. The research focus of Dr. Kovac's laboratory is to investigate cholesterol synthesis, metabolism and homeostasis. His research interest is nicely complimented by the research being pursued in Dr. Waterman's lab. His lab has been a leader in studying steroidogenesis and structure-functions of P450 enzymes. He is continuing studies of sterol 14ß-demethylase (CYP51), the cytochrome P450 monooxygenase that catalyzes the first step following cyclization in sterol biosynthetic pathways in all biological kingdoms. His group has shown that in postmeiotic male germ cells this enzyme is expressed at unusually high levels. Drs. Kovacs, Olson and Waterman have record of collaboration in specific projects. Drs. Matusik, Orbegin-Crist, Olson and Ong also have a record of extensive collaboration. Recently, Drs. Greenstein, Matusik and Orbegin-Crist have used proteomics approaches in their work by collaborating with Dr. Caprioli who is a world authority in studying in situ protein-protein interactions using MALDI-TOF mass spectrometry.

Uterine biology. Research programs on various aspects of uterine biology are a major strength at Vanderbilt. The research focus of Dr. Das's lab is to understand estrogen receptor (ER) dependent and independent functions of natural and environmental estrogens in uterine function. The focus of Dr. Dey's group is to better understand uterine functions modulated by growth factors, cytokines, Wnts and homeotic proteins as local mediators in response to ovarian steroid hormones. The recent research focus of Dr. Paria's lab is to examine the role of junctional proteins in mediating epithelial-mesenchymal interaction in the rodent uterus. The focus of the Dr. Ong's lab is to understand the role of vitamin A (retinoids), which are essential for proper functioning of both the male and female reproductive organs. In recent years, his focus has been directed to retinoic acid homeostasis as it relates to uterine biology. Dr. Osteen's groups' current research is to better understand the role of ovarian steroids in uterine matrix remodeling with special emphasis to metalloproteinases and endometriosis.

Preimplantation embryo development and implantation biology. This area of research represents a major form of a very strong group of investigators. The Das lab is currently pursuing research on the role of cell cycle regulatory molecules, calcium-binding and chaperon proteins in stromal cell decidualization and polyploidy at the molecular and genetic level. Dr. Dey's group is involved in defining the molecular and genetic basis of preimplantation embryo development and embryo-uterine interactions during implantation with particular reference to signaling by growth factors, cytokines, Wnt, homeobox, prostaglandin and endocannabinoid. The Paria lab is engaged in examining the role of decidual junctional proteins in protecting the implanting embryo from maternal insults and also the role of embryonic steroids in implantation.

Genetic regulation of gonadotropin secretion. The Phillips laboratory is currently working on the role of the PROP1 mutation in humans with idiopathic hypogonadotropic hypogonadism (IHH). This presents clinically with irreversible pubertal delay with low sex steroids, resulting from low serum levels of the pituitary gonadotropins FSH and LH. The pathophysiology of IHH involves hypothalamic and/or pituitary dysfunction, as gonadotropin levels are inappropriately low despite the hypogonadal state. Treatment of IHH is highly successful because replacement of the deficient sex steroids induces sexual maturation, and when coupled with GnRH or gonadotropins therapy, this usually results in normal fertility in both sexes. The genetic basis of IHH is largely unknown and is being pursued in the Phillips lab.

The participation of Drs. Arteaga, Caprioli, Carpenter, Moses, Osheroff and Sealy is in line with the NIH roadmap to multidisciplinary approaches to crossing traditional boundaries and bringing forward different conceptual frameworks and methodologies to make the training environment more competent to produce reproductive biologists for the 21st Century. The research focuses of Drs. Arteaga and Carpenter labs are to better understand the role and mechanism of signaling by EGF family of growth factors in cell function, development and tumorigenesis. The research interest of the Moses lab is to explore the epithelial-mesenchymal interactions with respect to TGF-ß signaling during normal and abnormal cell growth using the prostate as a model. It is well recognized that these signaling pathways are also critical to many reproductive functions. The Osheroff lab has been studying the role of topoisomerases in DNA replication, transcription, mitotic and meiotic recombination, and chromosome segregation during mitosis and meiosis. These events are inextricably linked to fundamental processes of reproductive biology and cell growth. For example, while topoisomerase I is required for oocyte development in Drosophila, topoisomerase IIIß is essential for embryogenesis in mice. The Caprioli lab is well known for its proteomic approaches in examining in situ protein-protein interactions within a cell or tissue. The Sealy labs' current research focus is to study the role of the transcription factor C/EBP-ß in development. Gene knock out studies have shown that this transcription factor is a key regulator of mammary gland development, since C/EBP ß null mice show severely impaired mammary gland development and do not lactate. Her lab is studying the differential role of C/EBP ß -1 and –2 in mammary gland development and differentiation.

These preceptors were selected because of their outstanding research programs, training histories, and significant contributions in their respective fields. Most importantly, the potential for establishing outstanding collaborative research environment to which the trainees will be exposed is high. Several collaborations (Caprioli with Greenstein and Orbegin-Crist) are already ongoing. The Dey lab has recently initiated collaborative projects with the Caprioli group to investigate in situ protein-protein interactions between implantation sites vs inter-implantation sites and uterine sites with implantation failure. The initial results are very exciting and hopefully rewarding to the trainees involved. There is enormous potential for collaboration of Das, Dey and Paria labs with those of Arteaga, Carpenter and Moses, because of common interests of these individuals in various signal transduction pathways in cell-cell communication, cell differentiation and development all of which occur during early pregnancy. Because C/EBP can regulate cyclooxygenase-2 (COX-2) expression and since COX-2 is essential for ovulation, implantation and decidualization, a potential collaboration between the Sealy and Dey labs is being planned to study the role of this transcription factor in regulating uterine COX-2 expression.

Although it goes against previous traditional approaches to good training, we firmly believe that a better training experience will be provided if a trainee is exposed to two or more different preceptor laboratories with different expertise and technologies to address a specific biological problem in reproduction. Thus, in a dramatic break from tradition it is planned that all trainees admitted to this training program will work jointly with a preceptor devoted to reproductive biology and a preceptor in related or other disciplines of research. We are offering a new dimension with this approach but basically each trainee will have a program designed to best meet her/his objectives in reproductive biology training for the 21st century. For example, Takiko Daikoku, a postdoctoral fellow in Dey's lab, worked with Caprioli’s lab to examine in situ protein-protein interactions between implantation versus inter-implantation sites by using MADI-TOF mass spectrometry. This has been a unique and productive experience for Dr. Daikoku and for the two labs. These types of interactions are expected to be the norm with the renewal of this RBTP training grant.

The commitment of Vanderbilt in invigorating the reproductive biology research is evident from the recent creation of a new Division of Reproductive and Developmental Biology in the Department of Pediatrics. Furthermore, fostering reproductive biology research at Vanderbilt is now a high priority in the strategic planning of the University. This will result in a rapid rise in clinical and basic research programs in reproductive biology in the next few years. Our Dean of the School of Medicine Dr. Steven Gabbe, who is the current president of the Society of Gynecological Investigation, is dedicated to this mission because of his own commitment to reproductive medicine. The strength of this group of assembled preceptors is its outstanding record of interactions and collaborations demonstrated by joint publications, grants and training of students. Furthermore, the national stature of this group is evident from continuous research support from federal agencies, their participation in NIH and NSF study sections, editorial boards of leading journals, and organizational committees for national and international symposia.


Reproductive Biology Training Program Faculty Members Information and Links

 

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Last modified: May 7, 2004

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