In vitro 3-D Ovarian Cancer Model for Understanding Interactions with Supporting Mesenchymal Stem Cells and High Throughput Drug Screening
Ovarian cancers, the leading cause of gynecological cancer mortality worldwide, have a high mortality rate of ~55%. Ovarian cancer is often undetected (due to lack of specific symptoms) until it has disseminated within the pelvis and abdomen. At such late stages, ovarian cancer is difficult to treat and is often fatal. One of the main reasons for the fatality of the ovarian cancer is the lack of physiological 3-D models that can unravel the relationships between the ovarian cancer cells and their supporting cells that could guide the screening of drug candidates against ovarian cancers. The malignant epithelial ovarian cancer cells are found in 3-D spheroids within peritoneal fluid in vivo. It is apparent that 3-D in vitro spheroid models of the ovarian cancer need to be created, to better understand the spheroid biology and contribute to the identiﬁcation of new treatment opportunities for metastatic ovarian cancers. In this project, we are working towards creating a 3-D in vitro model of ovarian cancer to probe the relationship between supporting mesenchymal stem cells and ovarian cancer cells, and how the synergy between interactions of these cells might increase the metastatic potential of ovarian cancers. We will use a variety of molecular biology approaches to discern the relationship between ovarian cancer cells and their supporting cells in a 3-D model of ovarian cancer. We will also screen drug candidates for their ability to treat metastatic ovarian cancers in this physiological model. The results from this project will have impact on the treatment strategies of ovarian cancers. Adult stem cells and animals are used in this laboratory.
Polymer based Tissue Engineering Models to Study Microenvironmental Control of HER2 Expression in Breast Cancers
Our lab is focused on creation of 3-D microenvironments by using microtechnology and biomaterials as engineering tools. The goal of this project is to develop in vitro systems where the factors of the extracellular matrix that drive metastasis of breast cancer cells can be carefully studied. We are developing polymer/hydrogel based breast cancer tissue engineering platform with precise 3D microscale cytoarchitecture and optimal cell-cell interactions between breast cancer cells and stromal cells (mammary epithelial cells, mesenchymal stem cells, fibroblasts, endothelial cells). This platform will provide 3D model of breast tumor environment that will be used to study and understand how the microenvironment physical properties and the spatial organization of cells and cell-cell interactions regulate expression of oncogenes such as HER2 in breast cancers. Adult stem cells and animals are used in this laboratory.
Modulation of Hematopoietic Stem Cell activity by Mechanical Stimulation
We are interested in determining if mechanical forces can impact hematopoietic stem cell (HSC) phenotypes. In the body, multipotent HSCs reside predominantly in the marrow cavities of bones in adult mammals and are localized to the osteoblast-lined endosteal niches and the pericyte-lined vascular environments. Bone is a dynamic organ, which responds to mechanical and physiological stimuli. In the bone, the response of osteocytes and osteoblasts to physical forces has been extensively studied. However, other cells within the marrow cavity are also subject to a mechanically active environment. In this project, we will build an in vitro model of the bone marrow that includes the HSCs and bone lining osteoblasts in a hydrogel matrix. In these in vitro engineered bone marrow microenvironments, we will quantify the response of HSCs to changes in the loading or unloading of the bone; as well as, exposure to tensile, compressive, and shear stresses in terms of their frequency, their retention of stem cell renewal potential, and their ability to form differentiated daughters of all lineages. Adult stem cells and animals are used in this laboratory.