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
