"Research is to see what everybody else has seen, and to think what nobody else has thought." -Albert Szent-Gyorgyi
2D optical slices of peri-implantation uterus
3D reconstruction of embryonic lung
Transverse folds in pre-implantation uterus
Isolating murine uterine contractions
Hormonal Regulation of Receptivity and Implantation
The uterine tube folds randomly in the absence of pregnancy but folds acquire a stereotypic pattern close to embryo attachment. Uterine folds also give rise to the implantation chamber that homes the embryos during attachment. We are using genetic mouse mutants, gene expression analysis and 3D imaging to understand how hormones guide the formation of uterine folds and how these pre-implantation folds affect the fate of the embryo post-implantation. (Arora et. al, Development, 2016 and Madhavan et. al, Development, 2022)
Uterine Gland Branching Morphogenesis
In a mammalian pregnancy, branched exocrine uterine glands nourish the embryo until the placenta forms. Estrogen receptor 1 signaling is critical for uterine gland branching and secretory function. (Granger, Fitch et. al, Molecular Human Reproduction, 2024). The uterine glands undergo patterning and reorganization at the time of embryo implantation. Using different image analysis platforms we are dissecting the structure of the uterine glands and the changes that accompany implantation. (Khan et. al, BioRxiv, 2024). Using spatial localization of the glands with respect to the other cell types, we will determine the functional consequences of these architectural glandular changes.
Quantitative Imaging and Modeling
We are using quantitative approaches to measure changes that occur in the uterine luminal and glandular architecture to prepare for pregnancy. We are also applying these methods to conditions where implantation fails to occur.
Mechanisms that regulate Embryo Movement
Embryos in mice display both unidirectional and bidirectional movement in the uterus before they undergo implantation. Embryo movement in mice is distinct from the unidirectional only movement observed in rats and rabbits. We are investigating how ovarian hormone signaling and muscle contractions modulate pre-implantation embryo movement. (Flores et. al, Development, 2020, Lufkin, Flores et. al, Molecular Human Reproduction 2022, Dawson, Flores, Zou et. al, Biology of Reproduction, 2024)
Mesenchymal regulation of embryonic lung development
The role of T-box genes in fetal development has been well established in the limbs, heart, and lung. Our lab uses a mouse model to study the fundamental biology of T-box transcription factors in airway epithelial and vascular development to better understand their role in progenitor cell fate specification and epithelial-mesenchymal crosstalk. This project will provide insights into the in-utero events that are disrupted in patients born with developmental lung disease associated with TBX4 mutations, further characterizing the pathophysiology of TBX4 Syndrome which will support subsequent investigations into therapeutics for this disease. (Arora et. al, PLoS Genetics 2012)