Assistant Professor of Biochemistry & Molecular Biology
215-762-3554
Mauricio.Reginato@Drexelmed.edu

Education:
Ph.D. (1998), Pharmacology
University of Pennsylvania

Research Program

Every year approximately 200,000 new cases of breast cancer are diagnosed, and 40,000 women are expected to die from this disease in the U.S. alone. One of the earliest events in breast cancer are changes in tissue architecture. In pre-cancer lesions such as carcinoma in situ, cells can proliferate and survive and consequently fill the luminal space and thereby change the normal ductal architecture. As some of these pre-cancers progress to invasive carcinoma, the basement membrane, made up of extracellular matrix (ECM) proteins, is disrupted and cells break out of the ducts and invade the surrounding tissue. Our lab is interested in identifying the molecular basis for early changes in tissue architecture related to breast cancer progression.

We are using a 3-dimensional (3D) basement membrane culture model in which cultured human mammary epithelial cells form growth-arrested, polarized, acini-like structures containing hollow lumens and thus recapitulating many architectural characteristics observed in normal mammary acini in vivo. The ECM plays a critical role in regulating breast tissue architecture and homeostasis, as cells require ECM for proper growth, differentiation and survival. In order to maintain normal tissue architecture, cells displaced from the ECM undergo apoptosis, referred to as anoikis. Tumor cells display significant resistance to anoikis, as they survive in the absence of matrix attachment and thus contributing to anchorage independence and metastasis. We are investigating how the major adhesion receptors, the integrin receptors in concert with oncogenes such as the ErbB-family tyrosine kinase receptors, regulate signaling pathways involved in cell survival, as well as cell growth and invasion, in 3D culture. Understanding these pathways will shed light on how tumor cells disrupt tissue architecture and may aid in identifying novel breast cancer markers and therapeutic targets.


Selected Publications

1. Sodunke, T. R., Turner, K. K., Caldwell, S. A., McBride, K. W., Reginato, M. J. and Noh, N. (2007) Micropatterns of Matrigel for Three-Dimensional Epithelial Cultures. Biomaterials 28:4006-16.

2. Reginato, M.J., and Muthuswamy, S.K. (2006) Illuminating the center: mechanisms regulating lumen formation and maintenance in mammary morphogenesis. J Mammary Gland Biol Neoplasia, 11:205-11.

3. Reginato, M. J., Mills, K. R.,Becker, E.B., Lynch, D.K., Bonni, A., Muthuswamy S., and Brugge, J. S. (2005) Bim regulation of lumen formation in cultured mammary epithelial acini is targeted by oncogenes. Mol. Cell. Biol. 25, 4591-4601.

4. Collins, N., Reginato, M. J., Paulus, J. K., Witt, A., LeBear, J., and Brugge, J. S. (2005) G1/S cell cycle arrest provides anoikis resistance through Erk-mediated Bim suppression. Mol. Cell. Biol. 25, 5282-5291.

5. Mills. K. R., Reginato, M. J., Debnath, J., Queenan, B., and Brugge, J. S. (2004) Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is required for induction of autophagy during lumen formation in vitro. Proc. Natl. Acad. Sci. USA, 101, 3438-3443.

6. Martin, S., Ridgeway, A., Pinkas, J., Lu, Y., Reginato, M. J., Koh, E., Michelman, M., Brugge, and Leder, P. (2004) A cytoskeleton-based functional genetic screen identifies Bcl-xL as an enhancer of metastasis, but not primary tumor growth. Cancer Research, 23, 4641-4645.

7. Reginato, M. J., Mills, K. R., Paulus, J. K., Lynch, D. K., Sgroi, D.C., Debnath J., Muthuswamy S., and Brugge, J. S. (2003) Integrins and EGFR coordinately regulate the pro-apoptotic protein Bim to prevent anoikis. Nature Cell Biology. 5, 733-740.

8. Debnath, J., Mills, K. R., Collins, N., Reginato, M. J., Muthuswamy S., and Brugge, J. S. (2002) The role of apoptosis in creating and maintaining luminal space within normal and oncogene expressing mammary acini. Cell 111, 29-40.