Charlotte Kuperwasser, PhD

Metaplastic breast carcinomas (MBCs) are a distinct aggressive form of estrogen receptor negative (ER-) invasive breast cancers that resemble tissues such as skin, bone, and cartilage. These cancers have a high rate of metastasis and few treatment options. Therefore, an understanding of the origins and mechanisms that give rise to metaplastic cancers is critical for the development of new therapies for this deadly form of breast cancer. Part of Dr. Kuperwasser’s long-term goal is to understand the molecular regulators of breast stem cells and how these cells make decisions to give rise to more mature cells with limited life span and growth potential. Ongoing research has led to remarkable molecular discoveries that have identified potential master regulators of stem cells that might be useful for targets in metaplastic and ER-negative breast cancer.

In 2012-2013, Dr. Kuperwasser will focus on two projects. The first is to understand the link between cellular reprogramming and early pre-malignant changes in human breast epithelial cells. The second is to define the transcriptional regulators of breast epithelial differentiation and stem cells, as these factors represent novel possible gene candidates that suppress differentiation. Dr. Kuperwasser’s team will perform functional and biological assays to determine their function and relevance and cancer. They will also collaborate with chemists to develop small molecule inhibitors as potential therapies for the treatment of breast cancer.

Mid-year Progress: Dr. Kuperwasser's team continues to make important advances on an innovative project supported by BCRF and has begun a new and exciting project using genome-wide functional screening to identify master regulators of human breast stem cells and differentiation. In their study aiming to understand the link between cellular reprogramming and early pre-malignant changes in human breast epithelial cells, they have begun to enumerate and characterize human breast tissue resident stem/progenitor cells that are likely the cellular precursors to breast cancer. In the past 6 months, Dr. Kuperwasser's group published a study in which they found that myoepithelial cells from adult human breast tissues can spontaneously reprogram back into surface ectodermal/epidermal stem cells that have lost the ability to make breast but now can generate self-renewing epidermal tissues such as skin but no longer form breast glandular structures. When transformed these cells give rise to metaplastic carcinomas.

Dr. Kuperwasser's laboratory has also performed sample analysis as well as labeling studies to determine directly whether the reprogrammed human mammary epithelial cells are pre-existing or arise de novo during in vitro culture. Based on their findings, they have been testing the hypothesis that loss of a proper microenvironment leads to spontaneous epigenetic reprogramming of a rare population of human breast basal/ME cells back into a more primitive state of embryonic development.

In their second project, Dr. Kuperwasser and colleagues are working towards identifying the repertoire of essential transcription factors (TFs) governing mammary epithelial differentiation and to determine how they regulate breast cancer phenotype and heterogeneity. Other activities related to this study are ongoing.

Bio:
Dr. Charlotte Kuperwasser is an Associate Professor in the Department of Anatomy and Cellular Biology at Tufts University School of Medicine and an investigator at the Molecular Oncology Research Institute (MORI) at Tufts Medical Center. She has been working in breast cancer research since her graduate training at the University of Massachusetts, Amherst, where she completed her PhD in 2000.

As a Jane Coffin Child's Postdoctoral Fellow in the laboratory of Robert Weinberg, she developed a novel humanized model to successfully recreate normal and neoplastic human breast tissues in laboratory models. In addition, she also developed another novel humanized model of human breast cancer metastasis to human bone.

Dr. Kuperwasser is a nationally recognized expert in breast cancer research, xenograft laboratory models, and the tissue microenviroment. Dr. Kuperwasser has received several awards including the COG/Aventis Young Investigator Award, the Raymond & Beverly Sackler Award, and the Natalie V. Zucker Award