Comprehensive Mechanisms in Reproductive Sciences T32

Principle Investigator: Stephanie A. Pangas, PhD

Sponsor: National Institutes of Health – Eunice K Shriver National Institute of Child Health and Human Development (NICHD)

OVERVIEW

Reproductive disorders, contraception, and family planning have major impacts on the health and well-being of individuals world-wide. The goal of this NIH-sponsored training program is to prepare young scientists to address these important problems through basic and translational research and in research-related careers that require expertise in reproductive biology. Baylor College of Medicine is a long-standing leader in reproductive biology research. The goal of our program is to provide the necessary skills and experience to prepare the next generation of scientists for successful and diverse careers in reproductive biology. 

Individual sperm tracking (colored line) towards ovulated eggs within the mouse ovary captured in vivo using optical coherence tomography. Image by Shang Wang, PhD, a former postdoctoral associate in the Larina Lab

PROGRAM DESIGN

This program supports two predoctoral and four postdoctoral trainees. The following is a summary of the training program:

  • Mentored state-of-the-art biomedical research training in some of the world’s premier reproductive biology laboratories.
  • Structured committees for both pre- and postdoctoral fellows guided by an Individual Development Plans (IDP) tailored to each trainee’s needs.
  • Wide-ranging career development activities though the Career Development Center
  • Activities to enhance skills in teaching, clinical/translational work, and entrepreneurship within the world’s largest medical center.
  • A mentored journal club that coincides with the Reproductive Biology Lecture series
  • An annual mini-symposium
  • Mentor-mentee training from facilitators trained from the NIH funded National Research Mentor Network
  • A novel “Ethics in Reproductive Health Learning Unit”

TRAINING FACULTY

Mouse sperm head by scanning electron microscopy. Left, normal mouse sperm head; Right, abnormal sperm head (globozoospermia) from a mutant mouse line. Figure by former pre-doctoral fellow D. Develin and postdoctoral fellow N. Nozawa in the Matzuk Laboratory.

Trainee mentors have been selected for contemporary research interests in reproductive biology and are currently supported by over $14 million in funding. Their research areas include studies of key reproductive biology proteins, normal and pathophysiology of male and female reproductive tissues, genetic and environmental factors that affect fertility, and translational research (male contraceptive development and developmental origins of adult disease). The training faculty use cutting edge approaches to study reproductive processes using genetic models, patient samples, in vitro models, and clinical data. The following principle investigators are part of this program:

Immunofluorescence imaging of ovarian defects in a mouse model of polycystic ovary syndrome. Image by Nicolas Candelari, a postdoctoral fellow in the Richards Lab. Published in the jouranl Endocrinology 2019 vol 160:137

PROGRAM RESEARCH THEMES:

Endocrinology and Hormone Action:  Studies are being conducted on the structure and function of molecules important for fertility in reproductive and other tissues. For example, recent studies include the first cryo EM structure of a steroid receptor (estrogen receptor complexed with coregulators), identification of a progesterone receptor phosphorylation site required for optimal fertility in mice, and testing potential endocrine disruptors for their effects on estrogen receptor action.

Structure of the Estrogen Receptor (ER)-SRC3-p300 complex on DNA by cryoEM. Study was published in the journal Molecular Cell 2015 vol 57 by the O’Malley laboratory

Reproductive Physiology:  Investigators study the normal physiology of reproductive organs such as uterus, ovary, male reproductive tissues using in vivo and in vitro model systems as well as clinical sample. Most PIs typically extend these to pathology of these same organs, including those that affect fertility, such as primary ovarian insufficiency and polycystic ovary syndrome.

Ovarian histology of wildtype (left) and a mouse with oocyte-specific deletion of an key enzyme in the SUMOylation pathway. Study by Amanda Rodriguez, a former PhD student in the Pangas Laboratory. Study was published in the journal, Development 2019.

Genetic and Environmental Factors:  These studies include those involved with genetic and environmental factors that affect reproductive function and fetal development, as well as the developmental origin of human adult disease. Studies range from identification of mutations that affect male and female reproductive tract development, fertility, as well as how diseases such endometriosis and diabetes alter fertility, pregnancy, and development.

Visualization of progesterone receptor expression in the uterus during pregnancy in the mouse. Images from postdoctoral fellows Maria Szwarc and Lan Hai in the Lydon Laboratory

Contraceptive Development and Drug Discovery:  Multiple investigators study male and female contraceptive target design and drug discovery. BCM is home to the Center for Drug Discovery, which includes state of the art screening to perform cell based-phenotypic and target-based biochemical assays. The Center currently has both DNA encoded chemical and small molecule libraries for use in large-scale screens.