Jeffrey M. Rosen, Ph.D.
Molecular and Cellular Biology
Stem cells in mammary gland development and breast cancer
Jeffrey M. Rosen, Ph.D., C.C. Bell Professor in the Departments of Molecular and
Cellular Biology and Medicine, received the award for his research directed towards
elucidating the mechanisms regulating normal mammary gland development, and how
these regulatory mechanisms have deviated in breast cancer. Specifically, in collaboration
with Dr. Peggy Goodell at Baylor College of Medicine, the Rosen laboratory was the
first to isolate functional mammary gland stem/progenitor cells. In collaboration
with Dr. Harold Varmus and his colleagues at Memorial Sloan Kettering, they also
have investigated the role of stem/progenitor cells in the etiology of several different
mouse mammary cancer models. These studies have led to the hypothesis that the clinical
and genetic heterogeneity of breast cancer is a result of the activation of different
oncogenes or loss of different tumor suppressor genes in specific stem/progenitor
cells. The Rosen laboratory has also demonstrated the importance of the Wnt/ß-catenin
pathway in mammary alveolar development, mammary stem/ progenitor cell self-renewal
and survival, and finally resistance to conventional radiation therapy. These studies
have important implications for our understanding of the etiology of breast cancer
as well as the design of new therapeutic agents targeted to putative “cancer stem
cells”.
Dr. Rosen’s nomination was based on the following publications:
Welm BE, Tepera SB, Venezia T, Graubert TA, Rosen JM, Goodell MA."
Sca-1( pos) cells in the mouse mammary gland represent an enriched progenitor cell
population. ". Dev Biol. 2002 May 1;245(1):42-56.
Li Y, Welm B, Podsypanina K, Huang S, Chamorro M, Zhang X, Rowlands T, Egeblad M,
Cowin P, Werb Z, Tan LK, Rosen JM, Varmus HE. "
Evidence that transgenes encoding components of the Wnt signaling pathway preferentially
induce mammary cancers from progenitor cells. ". Proc Natl Acad Sci U S
A. 2003 Dec 23;100(26):15853-8.
Lam MH, Liu Q, Elledge SJ, Rosen JM. "
Chk1 is haploinsufficient for multiple functions critical to tumor suppression.
". Cancer Cell. 2004 Jul;6(1):45-59.