Our lab focuses on investigating the molecular mechanisms that drive normal breast development and how these processes become disrupted in cancerous tissue. More specifically, we are interested in the role of stem and progenitor cells in both normal and carcinogenic development, especially the molecular drivers of breast epithelial differentiation. Previous work recently established the transcription factor Slug (SNAI2) as a luminal differentiation suppressor. My project seeks to determine the effect of aging on mammary progenitor cells, specifically in regard to the role of Slug as a regulator of breast epithelial differentiation. I am also working to show that this transcription factor may also have a novel function as an RNA binding protein.
Our lab has shown that lineage-committed mammary epithelial cells can have bipotent character by stimulating luminal cells to adopt a basal phenotype. My project focuses on elucidating whether the reverse of this phenomenon can be induced, namely I aim to study whether basal cells can acquire a luminal phenotype.
Breast tumors and other solid cancers do not exist in a vacuum and is a disease composed not only of cancer cells, but also the surrounding stromal cells making up the tumor microenvironment. My research interests are focused on the role of the surrounding fibroblasts in modulating the rigidity of the tumor microenvironment and its contribution to the promotion and progression of breast cancer.
Breast cancer is a heterogeneous disease that encompasses multiple subtypes, which differ in their molecular profiles, clinical course of progression, and response to therapeutics. Similarities between breast cancer subtypes and epithelial cell lineages found in the normal breast suggest that determining the identity and activity of normal breast cells could lead to a better understanding of both mammary cell biology and breast cancer. My research focuses on characterizing and classifying cellular subsets within epithelial cell lineages of the normal mammary gland to better understand the hierarchy of development from stem/progenitor to mature mammary epithelial cells and how disruption of this hierarchy could lead to breast cancer.
Project Title: “Functional Investigation of the Long Tail Drivers of Human Breast Cancer”
Cancer exome sequencing has revealed that 20% of cancers lack mutations in even a single known or putative driver gene, indicating that we must look to the “long tail” distribution of mutated genes in order to complete our knowledge of cancer genetics. Since it is currently unknown how long tail drivers impact the proliferative pathways commonly deregulated in cancer, the investigation of these drivers is of central importance for basic and translational cancer research. Throughout my doctoral and postdoctoral work, I have pioneered genetic technologies to identify long tail drivers. These early works have served as the foundation for my current focus, which is to ask how such drivers mechanistically cause the dysfunction of major proliferative signaling pathways in order to promote transformation and tumorigenesis.
Over the past several years, genome sequencing has led to unparalleled, multifaceted analysis of the genetic and molecular landscape of human cancer, in particular breast cancer. Ideally, this information could enable medical professionals to make better decisions regarding treatment regimes. Perhaps the most exciting potential of this new personalised medicine era is the ability to tailor drugs towards the characteristics of an individual’s tumour. However, in order to develop such therapeutics, we need to not only identify mutated genes but to also assemble and understand the regulatory pathways that are required for tumourigenesis. The aim of my project is to identify the potential pathways which are required for cancer initiation using the innovative Human-In-Mouse model pioneered by the Kuperwasser Laboratory. Using this model, we can study human breast cancer within the architecture of a mouse and provide more clinically relevant data. Identification of the genetic alterations that transform cells into a malignant state will provide novel potential therapeutic targets for treating tumours prophylactically.
B.S University of California, Davis
Basal-like breast cancer (BLBC) is an aggressive breast cancer subtype for which there is currently no effective targeted treatment. Our lab previously identified the transcriptional repressor Slug is frequently overexpressed in BLBC, and Slug is an important regulator of luminal differentiation. I carried out a chemical screen to identify potential homeostatic regulator(s) of Slug protein. In doing so, my goal is to pinpoint druggable regulators for developing rational therapeutic strategies to molecularly dampen Slug hyperactivity, and ultimately improve our abilities to treat and improve outcome of patients diagnosed with BLBC.
Associate Professor of Developmental, Molecular & Chemical Biology
Tufts University School of Medicine
Investigator Molecular Oncology Research Institute (MORI)
Tufts Medical Center
Dr. Charlotte Kuperwasser is the Director of the Raymond and Beverly Sackler Convergence Laboratory at Tufts University School of Medicine. She is an Associate Professor Developmental, Molecular & Chemical Biology and an investigator at the Molecular Oncology Research Institute (MORI) at Tufts Medical Center. She is a national and internationally recognized expert in the fields of mammary gland biology and breast cancer.
Dr. Kuperwasser has made seminal and important contributions in the field of mammary gland development, breast cancer, stromal-epithelial cell biology, and stem cells. Dr. Kuperwasser received her PhD at the University of Massachusetts, Amherst, and was a Jane Coffin Child’s Postdoctoral Fellow in the laboratory of Robert Weinberg at the Whitehead Institute for Biomedical Research at MIT. Dr. Kuperwasser has been a Howard Hughes Fellow, a Merck Fellow and received several awards including the COG/Aventis Young Investigator Award, and the Natalie V. Zucker Award.