Senior Advisor to the Laboratory Director
Lawrence Berkeley National Laboratory
Metastasis, the leading cause of death in breast cancer patients, occurs when cancer cells break away from the primary tumor, enter the blood or lymphatic circulation, travel to distant sites such as bone, brain or lung and establish themselves in a new environment called a ‘niche’. Disseminated tumor cells (DTC) can remain dormant for decades after treatment of the primary tumor, but little is known about how DTC become active after periods of dormancy. Dr. Bissell’s laboratory created a three-dimensional (3D) cell culture system that allows her team to study the complex interaction of tumor cells and other cell types in a laboratory setting. Using this model system, they are studying the processes involved in breast cancer cell invasion, metastasis and tumor cell dormancy. Previously, the Bissell team showed that the formation of new blood vessels stimulates dormant tumor cells to grow and multiply. In the coming year, they will concentrate on tiny circulating packages called exosomes that contain an abundance of proteins, RNA, and DNA. Research has shown that tumor cells produce large amount of exosomes, which can circulate in blood and fuse with other cells in distant tissues and promote metastasis. These studies therefore may reveal new predictive biomarkers and therapeutic targets for drug development.
Every cell in the mammary gland is surrounded by a microenvironment, which includes neighboring cells and tissue components called extracellular matrix (ECM) that together make up the architecture of the tissue. A dynamic and reciprocal conversation exists between each cell and its microenvironment to guide the development and maintenance of healthy tissue. Ductal carcinoma in situ (DCIS) is considered an early pre-cancerous lesion that occurs in the cells lining the milk ducts of the breast. How the different components of breast tissue – the cells lining the ducts, the tissue architecture and ECM – interact to prevent or even promote DCIS is still not well understood. In order to understand the changes leading to cancer progression it is imperative to understand the complexity of the normal breast. Dr. Bissell and BCRF colleague, Dr. Laura Esserman are engaged in a collaborative project in which they will use advanced technologies to isolate and characterize each cell type within the normal breast in an effort to identify patterns of similarity and differences between the diverse cell populations. They will then use a similar approach to study the cellular makeup of DCIS. Because tissue architecture plays a crucial role in the progression of breast cancer, they will use a three-dimensional culture system to study the types of colonies formed when cells from non-malignant vs. DCIS tissue are grown in specific microenvironment conditions. They will expand these studies to include estrogen receptor-negative in situ cancers for which there are no targeted therapies. These approaches may lead to a better understanding of the role of the different cellular components in normal physiology, how they give rise to DCIS and which DCIS lesions will progress into aggressive breast cancers.
Dr. Bissell has been a visionary and pioneer in the area of the role of extracellular matrix (ECM) and microenvironment in regulation of tissue-specific gene expression with special emphasis in breast cancer, where she has changed a number of established paradigms. She earned an AB with honors in chemistry from Harvard College and a PhD in bacterial genetics from Harvard University. She joined the Lawrence Berkeley National Laboratory in 1972, became Director of Cell & Molecular Biology in 1988, and was appointed Director of all of Life Sciences in 1992. Upon stepping down as the Life Sciences Division Director, she was named Distinguished Scientist. She has authored more than 380 publications, is a member of nine international scientific boards, and is on the editorial board of a dozen scientific journals. She has given more than 130 ‘named and distinguished’ lectures and was both a Fogarty and Guggenheim Fellow. She is a recipient of numerous awards and honors including the E.O. Lawrence Award, Medal of Honor of the American Caner Society and the Pezcoller-AACR award.
Dr. Bissell is an elected Fellow of the AAAS, e IOM, the American Academy of Arts and Sciences, the Philosophical Society, the Royal Society of Chemistry, the National Academy of Sciences and the AACR Academy. She has received honorary doctorates from Pierre & Marie Curie University in Paris and the University of Copenhagen.