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Mina J. Bissell, PhD
Senior Advisor to the Laboratory Director
Lawrence Berkeley National Laboratory
Goal: Identifying potential targets to prevent or treat the spread of breast cancer.
Impact: Dr. Bissell is examining the ways in which dormant cancer cells in breast cancer patients are “awakened” and metastasize. Her laboratory findings may reveal novel therapeutic targets and strategies to treat breast cancer patients and prevent breast cancer recurrence and metastasis.
What’s next: She and her team will continue to focus on exosomes—tiny particles shed from the surface of cells—and the role they play in tumor progression and metastasis.
Complex interactions occur in the network of cells and structures that surround a tumor (the microenvironment) that can prevent or promote tumor growth and spread. Dr. Bissell is studying how signals from the tissue and tumor microenvironment affect the signaling pathways inside breast cells that cause them to become malignant and what can be done to stop or reverse this process.
Full Research Summary
Research area: To understand how the signals from the microenvironment surrounding breast tumor cells affect tumor growth and metastasis.
Impact: Metastasis is a major cause of breast cancer related deaths. Although recent advances in cancer research have revealed how cancer cells leave the primary site and colonize other tissues, what happens to disseminated and dormant tumor cells in the interim is poorly understood. Tissue organization and signaling from the microenvironment are important to maintain cells in a non-malignant state. Therefore, Dr. Bissell is focusing on the role of the tissue architecture and microenvironment in the maintenance of normalcy or the ability of dormant cancer cells to “awaken” and begin to grow and spread to other sites. The results of her investigations will provide novel insights into the mechanism of tumorigenesis and metastasis as well as provide new avenues to pursue less toxic therapeutic targets for breast cancer treatment.
Current investigation: Dr. Bissell and her colleagues are determining how the tissue architecture signals breast cancer cells and allow the awakening of dormant cancer cells to grow and spread. They will focus on how extracellular vesicles called exosomes influence the metastatic potential of breast cancer cells.
What she’s accomplished so far: Dr. Bissell’s team have discovered that key regulators of the communication between the extracellular matrix and cells (laminins, nitric oxide, p53, and microRNAs) are required for establishing proper breast tissue structure. Moreover, delta133p53 a modified form of p53, was more highly expressed in nonmalignant cells than in malignant breast cells. Furthermore, they found that delta133p53 plays a role in modulating fibronectin (FN), one of the components of the extracellular matrix (ECM) which is involved in cell migration and invasion.
What’s next: The team will continue to focus on how different versions of the p53 protein influence tissue architecture and invasion, how growth factors affect cell behavior, and how exosomes participate in cell communication. They will also investigate how exosomes, which are increasingly shed with tumor progression, and the cargo they carry (growth factors, enzymes, nucleic acid, etc.) influence the behavior of cells even at distant sites of metastasis.
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 Cancer Society and the Pezcoller-AACR award.
Dr. Bissell is an elected Fellow of the AAAS, the 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. She received BCRF's Jill Rose Award for research excellence in 2011.