Research Divisions: Reproduction and Pelvic Floor Dysfunctions
(1) Prediction and prevention of Preterm Birth;
(2) The regulation of uterine functions during pregnancy and labour, specifically the role of mechanical and endocrine signals;
(3) The study of molecular mechanisms underlying the development of Pelvic Floor Disorders in pre- and post-menopausal women;
(4) Use of urine-derived induced Pluripotent Stem Cells (iPSC) from patients with PFD as a source of autologous cells for disease treatment.
(1) My research aims to improve the ability to predict Preterm Birth (PTB) by combining two complementary technologies (cervical MRI and blood immune markers) and to examine activation of immune cell subtypes in the maternal peripheral circulation; this creates a new research partnership by integrating transdisciplinary expertise in MRI imaging, immunology, and PTB mechanisms/diagnostics with the goal of developing a sensitive and specific novel screening tool to identify women at risk of PTB. This study will result in an improved understanding of the cervical events preceding delivery at term and preterm, in particular the molecular changes that mediate the cervical change in the mouse creating a model for human cervical change.
(2) My research goal is to investigate (i) mechanisms of myometrial and decidual activation during the initiation of preterm and term labour as well as (ii) the role of leukocyte-mediated myometrial inflammation in the initiation of labour. These investigations include the use of human and animal tissues, primary uterine smooth muscle cells, primary leukocytes, and endothelial cell lines. Whole animals are used to verify that the mechanisms, identified via the in vitro systems, are effective in vivo.
(3) My research examines (i) the contribution of mechanical stretch on the development of Pelvic Organ Prolapse and (ii) the potential protective effects of ovarian hormones on vaginal tissue deterioration. This knowledge will expand the diagnostic and clinical treatment capability, will provide strategies identifying women at risk of developing POP, and will determine whether risk factor modification prevents the development of pelvic floor disorders in such women improving their quality of life and reducing general health care costs.
(4) Collection of viable cells from voided urine samples of women with PFDs, reprogramming them to iPSC lines under xeno-free conditions, and lineage-specific differentiation into autologous skeletal muscle cells and smooth muscle myocytes (for SUI) and fibroblasts (for POP). This novel approach provides an absolutely non-invasive method for gaining large numbers of patient-matched cells for regenerative medicine.
Animal Models of Obstetrical/Gynecologic Events: artificial menopause, pseudopregnancy, unilateral pregnancy, progesterone-delayed labour, infection-induced and sterile PTL models.
Procedures: (1) animal surgery (ovariectomy, unilateral tubal ligation, intrauterine infusion, intrauterine tubal insertion), (2) isolation of primary human myometrial cells, human vaginal cells, human decidual cells, rat myometrial cells; (3) isolation of total leukocytes from human peripheral blood, isolation of sub-populations of peripheral monocytes, lymphocytes, granulocytes, plasma, buffy coat.
Experimental Methods: Gene expression analysis (Northern blot, qRT-PCR, RT2 Profiler PCR array, RNAseq), protein expression analysis (Western immunoblotting, Immunoprecipitation, ELISA, Luminex assay, Zymography, Quantibody protein array, O-link), Flow cytometry; FACS, in situ protein localization (Proximity Ligation Assay, immunohistochemistry, Immunocytochemistry, fluorescent immunostaining), histology (H&E, Masson trichrome staining), tissue culture, cell culture, derivation of iPSCs, MRI.
Vacuum-driven Flexcell computer system (FX-5000 Strain Unit, Flexcell International Corp., NC, USA), Bio-Plex® 200 System (Bio-Rad Laboratories Inc., CA, USA), CFX384 Real Time System C1000 Thermal Cycler (Bio-Rad Laboratories Inc.), Experion™ RNA Analysis Automated System (Bio-Rad Laboratories Inc.), NanoDrop 1000 Spectrophotometer (Thermo Fisher Scientific), microscopes (Leica), centrifuges (Eppendorf), Ep-motion robot (Eppendorf automated liquid handling system), TissueLyser (Quigen).