Current Projects
Modeling the metabolic heterogeneity of HGSOC in 3D
Tumor cells can shift their metabolism to increase their metastatic potential and meet their high energetic demands. For example, cancer cells can increase their glycolytic and OXPHOS metabolism to increase ATP production, which is involved with cancer growth, metastasis, and chemoresistance. We aim to model the tumor microenvironment and metabolic heterogeneity of high-grade serous ovarian cancer (HGSOC) in 3D to better understand the effects of metabolism in epithelial ovarian cancer, specifically OXPHOS inhibition. We use tumor spheroids as a 3D model of HGSOC to recapitulate multiple cell populations and metabolic heterogeneity of a solid tumor in a single model. To inhibit OXPHOS, we treat HSGOC spheroids with atovaquone, which is a model compound for OXPHOS inhibitors. Atovaquone is an FDA-approved drug used in clinic to treat malaria and is generally well tolerated. It also has anti-cancer effects in vitro and in vivo in HGSOC. We study the effects of atovaquone by looking at invasion and migratory patterns of the spheroids, endothelial vessel permeability, and HGSOC cell function.
Primary Preeclampsia Cell Longevity for In Vitro Model Development
We aim to investigate how the phenotype of human preeclampsia (PE) endothelial cells change over multiple passages. We are using a single-lumen microphysiological system to create PE endothelial cell vessels in vitro. We aim to interrogate the capacity of healthy and PE endothelial cells to maintain their phenotype as a way to determine the longevity of primary cells for use in disease model systems.
3D model of the omental microenvironment to understand the crosstalk between HGSOC cells and adipocytes to identify therapeutic targets in HSGOC
The omentum, a fatty tissue that lays on top of the intraperitoneal organs, is the most common metastatic site for HSGOC. Omental adipocytes provide growth factors, inflammatory cytokines, and fatty acids that may be critical for HGSOC cells to invade and proliferate in the omentum, leading to tumor progression. This project aims to model the omental microenvironment in a microphysiological system (MPS) to better understand the crosstalk between the components of the omentum, adipocytes, and the ovarian cancer cells, including their importance in promoting metastasis and identification of potential drug targets.
Development of a New 3D Microfluidic model of STIC Lesions
Understanding the progression of precancerous STIC lesions in the fallopian tube to high-grade serous carcinoma (HGSC) is hindered by their small size and the lack of standardized detection methods, limiting our knowledge of the underlying molecular mechanisms. Recognizing the clear and pressing need for in-vitro models, we are developing and characterizing a microfluidic device capable of constructing blind tubular structures (lumens) embedded in hydrogel, mimicking the ovarian fimbria structure and enabling the study of cell migration relevant to STIC lesion development.
Investigating the Role of T-cells in Fueling Preeclampsia-Driven Vascular Dysfunction
Identifying the mechanisms between the immune system and the endothelium in the hypertensive preeclampsia decidua. We aim to elucidate how vascular dysfunction is established in the preeclampsia decidua by interrogating the direct and paracrine effects of hypertensive PBMCs on decidual endothelial cells. This project will use patient-specific decidua cell samples and engineered microphysiological systems to recreate decidua-lymphocyte interactions in vitro.
Comparison of resin and PDMS for microfluidic applications
PDMS is highly permeable to both lipophilic and apolar agents, limiting its ability in drug assays. The aim is to characterize the use of 3D-printed resin for cell culture and microfluidic applications as a base and supplement for devices. Done by testing the cell viability of resin and the absorbance of lipophilic/apolar agents as an alternative to PDMS.
Investigating the Effect of Gynecological Cancers on Lymphatic Vessel Integrity
We aim to assess how gynecological cancers disrupt lymphatic vessel function via either co-culture of HLEC vessels with ovarian cancer spheroids or treatment of lumens with spheroid conditioned media.