Charlotte Kuperwasser, PhD Principal Investigator 617-636-2364 Charlotte Kuperwasser BS, Biochemistry, University of Massachusetts-Amherst, Amherst, MA PhD, Molecular & Cellular Biology, University of Massachusetts-Amherst, Amherst, MA Postdoctoral Training, Whitehead Institute/MIT, Cambridge, MA My laboratory uses various animal models, including human xenograft models and other strategies to understand the genetic and epigenetic pathways involved in human breast cancer development, invasion and metastasis, with the emphasis on stromal-epithelial interactions. We aim to identify key stromal regulators that may ultimately be used for drug development to prevent or treat breast cancer.

Lisa Arendt, DVM, PhD Senior Research Associate Lisa Arendt           Theresa DiMeo Graduate Student 617-636-5644 Theresa DiMeo BS, Biochemistry, University of Massachusetts-Amherst, Amherst, MA Breast cancer metastasis is the most frequent cause of mortality associated with the disease, even if the primary tumor has been resected. Approximately 10-15% of patients have an aggressive disease and will succumb to metastatic spread within three years of the initial diagnosis. Our lab has developed a model system to study metastasis using a human breast cancer cell line, SUM1315. These cells are highly invasive and metastatic to both human implanted bone1 and mouse lung.  We isolated and cultured the cells that metastasized to lung, establishing a subline we called SUM1315 LP1. When injected orthotopically, the LP1 line metastasized more quickly and with more efficiency than the parental line. A microarray was performed comparing the tumor formed from the LP1 injection and the cells that formed nodules in the lungs. From this microarray, we found a number of genes from the Wnt pathway that were differentially expressed in the metastatic lungs compared to the primary tumor. More specifically, many genes downstream of the transcriptional co-activator β-catenin were downregulated in the lungs, while genes from the noncanonical (Wnt-JNK) pathway were upregulated. We are currently working to characterize the Wnt signaling activities in the metastatic cells to determine how the differential regulation of these two pathways is implicated in breast cancer metastasis.

Vandana Iyer, PhD Postdoctoral Fellow 617-636-5644 B.S. Cell & Developmental Biology, University of Rochester, Rochester NY Ph.D. Cell Biology, Albany Medical College, Albany NY Our lab has demonstrated that an increase in the levels of circulating estrogen (such as that found following pregnancy) promotes the formation and progression of ER-negative cancers through a systemic enhancement of host angiogenesis.  In addition to the systemic increase in angiogenesis, there is an increase in the recruitment of bone marrow derived cells into the growing tumor mass.  My project will focus on identifying which type of bone marrow derived cell is the target of estrogen-mediated angiogenesis and tumor promotion as well as the mechanism by which estrogen influences these cells through both in vitro and in vivo methods.

Patricia Keller, PhD Postdoctoral Fellow 617-636-5644 Patricia Keller B.S. Biochemistry and B.S. Molecular Biology, University of Wisconsin-Madison Ph.D. Pharmacology, University of North Carolina-Chapel Hill

Ina Klebba Senior Research Technician 617-636-5644 Ina Klebba Establishing a model system that more accurately recapitulates both normal and neoplastic breast epithelial development in rodents is central to studying human breast carcinogenesis. However, the inability of human breast epithelial cells to colonize mouse mammary fat pads is problematic. In light of the fact that the human breast is a more fibrous tissue compared to the adipose rich stroma of the murine mammary gland, our group sought to bypass the effects of the rodent microenvironment through incorporation of human stromal fibroblasts. As a result, we have been successful in reproducibly re-creating functionally normal breast tissues from reduction mammoplasty. In addition, we have also been successful in recreating tumor tissues from patient-derived samples as well as through genetic engineering, in what we term the Human In Mouse (HIM) model. As the senior animal technician in the lab, my focus is to apply this model system towards understanding the biology of normal human breast development and tumorigenesis. In addition to the application of the HIM model to address questions regarding human breast stem cells, heterotypic interactions and cell type of origin in breast cancer development, I am also centrally involved in all the other in vivo models employed in the lab to study metastasis and systemic and endocrine effects in breast cancer formation. Amy Lin Graduate Student         Xiang Liu, PhD Postdoctoral Fellow         Jessica McCready, PhD Postdoctoral Fellow         Jennifer Rudnick Graduate Student Jennifer Rudnick           Kai Tao Research Associate           Maja Sedic Graduate Student