Avi Z. Rosenberg

5th Year Graduate Student

Department: Cold Spring Harbor Laboratory

Graduate Program: Genetics

Advisor: Dr. Senthil Muthuswamy

Abstract:

Title:  The Polarity Regulator Scribble Regulates Cell Fate in Mammary Epithelial Cells

The purpose of our study is to understand the role of novel polarity regulators in mammary gland development and their ability to cooperate with oncogenes in tumorogenesis within this gland. We are using mouse systems to understand the role of a particular gene, Scribble, in this process and have identified a role for scribble in cell fate decisions and mammary gland morphogenesis.

In a normal mouse cell line, Comma-1D, using RNAi technology we have observed a morphological change, with cell fate shift towards basal population expansion in scribble knockdown cells. Scribble knockdown also impacts morphology of the outgrowth in a fat pad transplantation model with reduced tertiary (side branches) indicating reduced lobuloalveolar development. This indicates that Scribble regulates differentiation of a progenitor or transit amplifying cell into the lobuloalveolar component of the breast.

This data is significant as it demonstrates the role of a polarity gene, Scribble, in the differentiation of the breast as well as the process by which differentiation occurs. It also provides the first in-vitro model for asymmetric cell division in a mammalian system and potentially allows us to link apical basal polarity regulators with planar polarity regulation.

Publications:
(MSTP-supported publications indicated with an *)

*Aranda V, Haire T, Nolan ME, Calarco JP, Rosenberg AZ, Fawcett JP, Pawson T, Muthuswamy. SK (2006) Par6-aPKC uncouples ErbB2 induced disruption of polarized epithelial organization from proliferation control. Nature Cell Biology. (In press)

Abstracts:

*Xiang B, Rosenberg A, Muthuswamy S. Rapid Mouse Models to Investigate Genetic Interactions During Mammary Tumorigenesis Era of Hope, Department of Defense- Breast Cancer Research Program Meeting, Philadelphia, PA, June 8-11, 2005 (Poster)

DiResta G; Brown H; Aiken S; Rosenberg AZ; Seif N; Doty S; Wright T; Lee S; Shanbahg A; Hawkins M; Healey J. A Bioabsorbable Membrane for Introducing UHMWPE Debris into the Bone-Cement Interface. Orthopaedic Research Society, 47th Annual Meeting, San Francisco, CA, February 25-28, 2001. (presented/ patent pending)