BME PhD Prospectus Presentation: Katalina Bustamante

Title: "Investigating the Mechanobiological Response of Menstrual Effluent-derived Endometrial Stromal Cells "

Advisory Committee: Irving Bigio, PhD – BU BME (Advisor) Darren Roblyer, PhD – BU BME (Chair) Michelle Sander, PhD – BU ECE

Abstract: Infertility and pregnancy complications in women can be influenced by abnormal uterine processes during the menstrual cycle. Decidualization is a spontaneous differentiation process that occurs in the endometrium essential for supporting fetal development in the event of pregnancy.  Endometrial fibrosis arising from pathologies like endometriosis or intrauterine adhesions, can dysregulate the decidualization process and lead to complications such as recurrent pregnancy loss, preeclampsia, or pre-term birth. The pathological matrix environment involved in fibrosis is driven by transforming growth factor receptor beta-1 (TGFβ-1) and a stiff extracellular matrix. In fibrosis of the kidneys, skeletal muscle, and derma, Yes-associated protein (YAP) has emerged as a mechanoregulator of the canonical TGFβ/SMAD pathway. Although research in the endometrium suggests a cooperation between YAP and SMAD in response to TGFβ-1, the mechanochemical synergy between matrix stiffness and TGFβ-1 signaling is poorly understood in human endometrial stromal cells (hESCs).  Modeling the endometrial environment using primary hESCs can be clinically restrictive due to the invasive nature of gold standard endometrial biopsies. Menstrual effluent (ME) is a noninvasive and readily available source of endometrial cells that addresses this limitation. Moreover, culturing ME-hESCs on a mechanically tunable polyacrylamide hydrogel platform can enable more mechanistic studies to understand the YAP-SMAD axis in a fibrotic endometrium. In this proposal I will investigate the mechanobiological response of ME-hESCs in a fibrotic microenvironment by (1) Characterizing ME-hESCs, (2) Determining the coupled effects of TGFβ-1 and matrix stiffness on decidualization, and (3) Evaluating YAP-SMAD as a therapeutic target for rescuing decidualization.