Charlotte Kuperwasser, PhD

To date, Dr. Kuperwasser's team has identified breast cancer "stem cells" in many different human breast cancer cell lines. They have shown that these cells have the ability to give rise to tumors with as few as 100 cells and the tumors they form resemble the human breast cancers. In addition, while these cells fuel tumor growth, the researchers have found they are not rapidly dividing. As a consequence they have shown that these breast cancer "stem cells" are resistant to chemotherapy yet surprisingly were more sensitive to radiation. They are now using these cancer stem cells as targets to identify anti-breast cancer drugs, particularly those that may eradicate or even prevent breast cancer metastasis to bone, brain and lung.

It is reported that 4%-45% of patients with early stage breast cancer already have disseminated breast cancer cells that do not appear to be growing in the bone marrow by the time the primary tumors are surgically removed. Despite the removal of the primary tumor, relapse in these patients and metastases at distant sites such as bone, lung, and brain is still the major obstacle in the clinic. Recently, the Kuperwasser laboratory developed several models of human breast cancer metastasis to lung, brain and human bone. They have shown that a population of breast cancer stem cells can be found in a variety of the human breast cancer cell lines that are used in these models of metastasis.

Furthermore, they have observed that these cells are resistant to Paclitaxel (Taxol) and 5-Fluorouracil (5-FU), both commonly used chemotherapies for the treatment of breast cancer. They now wish to extend this work by understanding how cancer stem cells survive and expand in the bone marrow, brain and lung tissues. This will identify important novel anti-cancer treatments that could prevent the expansion of breast cancer cells in secondary tissues.

Mid-Year Progress Report:
With the support of BCRF, Dr. Kuperwasser’s team has been working towards understanding the effect of hormones on the cells that fuel breast tumor growth and metastasis, namely cancer stem cells (CSCs). During the course of characterizing the dynamics of cancer stem cells in culture, they observed that the percentage of CSCs cells varied, depending on the presence or absence of certain types of hormones. They are currently working towards identifying the mechanism by which estrogen exerts this effect to ultimately target expansion of the cell population that fuel tumor growth and metastasis.

Bio:
Dr. Charlotte Kuperwasser joined the faculty of Tufts University School of Medicine in 2004 and holds a tenure-track position as an Assistant Professor in the Department of Anatomy and Cellular Biology. She also holds a secondary appointment in the Department of Radiation Oncology at Tufts-NEMC, and is an investigator at the Molecular Oncology Research Institute (MORI) at Tufts-NEMC. She has been actively working in breast cancer research for nearly a decade beginning during her graduate training at the University of Massachusetts, Amherst, where she completed her PhD in 2000. Her thesis work focused on establishing a laboratory model of Li-Fraumeni Syndrome (a hereditary cancer syndrome in which breast cancer is one of the most common tumor types), demonstrated for the first time that hormones may regulate the function of p53 in the breast epithelium.

She continued to study breast cancer research during her postdoctoral training at the Whitehead Institute in the laboratory of Robert Weinberg, where she developed a novel humanized model to successfully recreate normal and neoplastic human breast tissues in laboratory models. This work demonstrated the importance of the human breast stromal cells in the normal development of human breast epithelium as well as in the promotion of pre-neoplastic and neoplastic growth. In addition, she also developed another novel humanized model of human breast cancer metastasis to human bone.

Since joining Tufts University and the Sackler School of Graduate Biomedical Sciences, Dr. Kuperwasser has established three main programs to study breast cancer pathogenesis in her laboratory that she feels demonstrate a greatest potential for clinical translation.