We aim to answer questions important in ensuring maternal-fetal health.
Welcome to the Mahendroo Lab.
Beginning in early pregnancy, the cervix initiates a remarkable transformation from a closed rigid structure to one at term that can open to allow safe passage of a fetus. We study the molecular events that drive this process in a term pregnancy and how perturbation of these processes contribute to premature birth. Leveraging single-cell genomics, tissue biomechanics, imaging and mutant mouse models we aim to answer questions important in ensuring maternal-fetal health.
Our Research
How do Steroid Hormones modulate Cervical Extracellular Matrix Structure and Function in Pregnancy?
The cervix is rich in extracellular matrix proteins and we know that changes in the composition and structure of this ECM determines the biomechanical function of the cervix. We also know that the steroid hormones progesterone and estrogen, in part, regulate the dynamics of ECM reorganization but we don’t understand how. We apply molecular, cell biology and tissue mechanical approaches in mouse models with defects in assembly of collagen and elastic fibers in the cervix to address these questions. This work is done in collaboration with the laboratory of Kristin Myers in the Department of Mechanical Engineering at Columbia University, NY, NY.
How does the Cervical Epithelial Barrier Protect against Ascending Infection?
The focus of this project is to understand the unique physical and immuno-protective barrier properties of the cervical epithelia during pregnancy. We have previously demonstrated that mice with a disrupted cervical epithelial barrier due to loss of hyaluronan synthesis are prone to an ascending infection-induced preterm birth. Using mice lacking hyaluronan in the female reproductive tract, single cell genomics and human cervical epithelial cell lines, we aim to uncover how the cervical epithelia protect against ascending infection.
Can we monitor cervical changes using novel imaging methodologies to predict preterm birth?
Using second harmonic generation imaging (SHG), we have demonstrated a gradual and progressive change in the organization of collagen fibers over the course of pregnancy. Since collagen is the main structural protein in the cervix, monitoring its changes over pregnancy may be useful to predict premature changes that ultimately lead to preterm birth. Ongoing collaborations with Xingde Li, a biomedical engineer at Johns Hopkins University are aimed at developing minimally invasive imaging applications that may be a useful clinical tool to predict premature cervical remodeling and preterm birth.
What is the mechanism of Infection-mediated Premature Cervical Remodeling?
Understanding the specific molecular events that drive preterm birth is necessary to find ways to detect risk of preterm birth as well as to develop targeted therapies for prevention. We have previously demonstrated that premature cervical remodeling induced by inflammation is achieved by pathways that are distinct from term cervical remodeling. Our ongoing studies aim to further this understanding and explore the molecular regulation of this distinct pathway.
What are the Spatio-Temporal Drivers of Cervical Remodeling in Pregnancy and Parturition?
In this project we employ single cell genomics to define the cellular states of cervical cells during normal pregnancy and parturition and to determine the molecular drivers of these cell states. This project is in collaboration with the laboratory of Gary Hon in the Green Center for Reproductive Biological Sciences at UTSW.
How do Estrogen and Relaxin Collaborate to Drive Gene Regulation in the Myometrium and Cervix during Pregnancy?
Numerous physiological processes in pregnancy require the combined actions of estrogen and relaxin. The goal of this study is to delineate the molecular mechanisms underlying functional interplay between estrogen and relaxin at the molecular and physiological levels in the myometrium and cervix. This study utilizes genomic approaches (RNAseq and ChIPseq) and physiological studies using mice with targeted mutations in the relaxin receptor. This project is being done in collaboration with Lee Kraus, Director of the Green Center for Reproductive Biological Sciences at UTSW.
