TMEN Programs

Program Area

Bioengineering 3-D Models for Breast Cancer Therapy
PI Name: BISSELL, MINA Institute: UNIVERSITY OF CALIF-LAWRENC BERKELEY LAB Co-PI: Catherine Park M.D. Collaborators: Nancy Boudreau, Ph.D., Kevin Healy, Ph.D. (with Paraic Kenny and Mark LaBarge, Post-doctoral Fellows) To understand diseases such as cancer, especially in organs that rely on epithelial-stromal crosstalk, and to find effective therapeutic agents, we must also understand how these different cell types and factors communicate with each other. Breast cancer manifests itself in the mammary epithelium, yet there is good evidence that other cell types of the mammary gland (myoepithelial, stromal, endothelial and immune cells) also play important roles in tumorigenesis. It is now becoming more widely appreciated that, as with other organs, the biogenesis of the breast tumor is the net result of interaction between the tumor epithelial cells, the microenvironment including these other cell types and the inflammatory mediators. Despite having established a robust assay for reproducing the distinction between normal epithelial and malignant epithelial breast cells in 3D, having demonstrated the supreme dominance of the microenvironment in manifesting the malignant phenotype in 3D assays or in mice, having discovered that signaling pathways are regulated differentially in 2D and 3D, serious questions remain: How close are we to recreating a model for human breast cancer both for understanding the mechanisms, but more importantly and urgently also for discovery of novel drugs and targeted therapies? Are there intrinsic differences in the tumor cells themselves or their microenvironments that lead to differential responses to chemotherapies? Accordingly, we propose the following aims:Aim 1: To develop functional co-cultures consisting of multiple human cell types using designer microenvironments that utilize both natural ECM molecules and biomimetics to create approximate organ models of normal and malignant breast in 3D. (Lead Investigator Mina Bissell. Co-investigators: Kevin Healy, Nancy Boudreau, with Genee Lee and Paraic Kenny) Aim 2: To dissect the role of the microenvironment in directing “mammary-specificity” in both homeostasis and in breast cancer response to chemotherapeutic drugs. With respect to the latter, we will also investigate if stem-like cells in tumor populations are enriched after some drug treatments signifying resistance due the existence of these precursors. (Lead Investigator Mina Bissell, Co-Investigator Kevin Healy, with Mark LaBarge, Celeste Nelson and Adam Carroll).

Bioengineering 3-D Models for Breast Cancer Therapy

PI Name: BISSELL, MINA
Institute: UNIVERSITY OF CALIF-LAWRENC BERKELEY LAB
Co-PI: Catherine Park M.D. Collaborators: Nancy Boudreau, Ph.D., Kevin Healy, Ph.D. (with Paraic Kenny and Mark LaBarge, Post-doctoral Fellows)

To understand diseases such as cancer, especially in organs that rely on epithelial-stromal crosstalk, and to find effective therapeutic agents, we must also understand how these different cell types and factors communicate with each other. Breast cancer manifests itself in the mammary epithelium, yet there is good evidence that other cell types of the mammary gland (myoepithelial, stromal, endothelial and immune cells) also play important roles in tumorigenesis. It is now becoming more widely appreciated that, as with other organs, the biogenesis of the breast tumor is the net result of interaction between the tumor epithelial cells, the microenvironment including these other cell types and the inflammatory mediators. Despite having established a robust assay for reproducing the distinction between normal epithelial and malignant epithelial breast cells in 3D, having demonstrated the supreme dominance of the microenvironment in manifesting the malignant phenotype in 3D assays or in mice, having discovered that signaling pathways are regulated differentially in 2D and 3D, serious questions remain: How close are we to recreating a model for human breast cancer both for understanding the mechanisms, but more importantly and urgently also for discovery of novel drugs and targeted therapies? Are there intrinsic differences in the tumor cells themselves or their microenvironments that lead to differential responses to chemotherapies? Accordingly, we propose the following aims:Aim 1: To develop functional co-cultures consisting of multiple human cell types using designer microenvironments that utilize both natural ECM molecules and biomimetics to create approximate organ models of normal and malignant breast in 3D. (Lead Investigator Mina Bissell. Co-investigators: Kevin Healy, Nancy Boudreau, with Genee Lee and Paraic Kenny)

Aim 2: To dissect the role of the microenvironment in directing “mammary-specificity” in both homeostasis and in breast cancer response to chemotherapeutic drugs. With respect to the latter, we will also investigate if stem-like cells in tumor populations are enriched after some drug treatments signifying resistance due the existence of these precursors. (Lead Investigator Mina Bissell, Co-Investigator Kevin Healy, with Mark LaBarge, Celeste Nelson and Adam Carroll).

	Help \| Contact Us \| Accessibility