Jeffrey M. Rosen, Ph.D.
C.C. Bell Professor of Molecular and Cellular Biology
The research objectives of the Rosen laboratory are to elucidate the mechanisms regulating normal mammary gland development, and to determine how these regulatory mechanisms have deviated in breast cancer. The laboratory is studying the role of systemic hormones, specifically prolactin, estrogens and progestins, and local growth factors, including members of the Wnt and Fgf families, on these processes. The role of specific transcription factors and their dominant-negative isoforms, including members of the C/EBP and Stat families, are also being examined using transgenic and knockout mouse models. Genetically engineered mice, coupled with FACS analysis and transplantation into the cleared mammary fat pad, have been employed as model system in which to isolate and characterize functional mammary stem/progenitor cells. Transgenic and knockout mouse models coupled with lentiviral transduction gain- and loss-of-function experiments are being used to elucidate changes in normal mammary gland stem cells and progenitors and signal transduction pathways that are involved in the progression from the normal mammary gland to pre-neoplasias. Unique preclinical syngeneic mouse models representative of the different human breast cancer subtypes are being employed to study the response of both primary tumors and metastases to combinatorial therapies focusing on the response of tumor initiating cells. These studies are being translated into the clinic to understand the mechanisms of therapeutic resistance of cancer stem cells to chemotherapy and radiation. Finally, studies are underway to elucidate the mechanisms by which noncoding RNAs, both miRNAs and lncRNAs regulate mammary gland development and are altered in breast cancer.