The Freeman Lab

Martin Hager Martin H. Hager, M.Sc., Ph.D.
DOD PCRP Fellow
Staff Scientist
Children's Hospital Boston

John F. Enders Pediatric Research Laboratories
300 Longwood Avenue
Boston, MA 02115
617-919-2022 (office)
617-730-0238 (fax)
Martin.Hager@Childrens.Harvard.edu

Hager research An important hallmark of advanced cancer is the loss of epithelial tissue architecture and the progression to invasive, metastatic disease with dissemination of single cancer cells that display mesenchymal morphology. This epithelial-mesenchymal transition (EMT) is characterized by loss of cell-cell adhesion and apical-basal cell polarity and results in a population of tumor cells with high motility. Whereas the importance of EMT is widely accepted and well studied, the role of cell polarity in carcinogenesis and metastasis is not well understood.

I am studying the links between growth factor signaling, receptor endocytosis, cell polarity and cancer metastasis. Regulators of cell polarity are frequently lost or become deregulated during carcinogenesis resulting in disorganized tissue structures. Although loss of cell polarity was previously considered to be merely a consequence EMT, recent evidence supports the idea that disruption of cell polarity mechansisms can play a causal role in tumorigenesis. Interestingly, the loss of cell polarity itself has been reported to provoke upregulation of important signaling pathways. To further understand the underlying molecular mechanisms, I use organotypic, 3-dimensional cell culture assays that recapitulate polarized epithelial morphogenesis in vitro in concert with in vivo metastasis assays.

Positions and honors

Positions
2003-2005	Postdoctoral Fellow, National Cooperative Drug Discovery Group, School of Pharmacy, University of Wisconsin, Madison, WI
2006	Research Fellow, Department of Urology, Children’s Hospital Boston and Harvard Medical School, Boston, MA

Selected Awards
2002	Research grant, Ministry of Science and Education, Innovations by Young Scientists Program, "Development otf a screening system for inhibitory ligands of the human Epidermal Growth Factor Receptor in yeast".
2003	Postdoctoral research fellowship (BMBF-LPD 9901/8-82), German Academy of Scientists, "Synthesis of new bioactive compounds by development of glycosyltransferases with altered substrate specificity".
2006	Prostate Cancer Training Award (Principal Investigator, PC061145), Department of Defense, Prostate Cancer Research Program (PCRP), "Membrane Heterogeneity in Akt Activation in Prostate Cancer".
2007	American Urological Association Foundation Research Program Scholarship, sponsored by the AUA Foundation Prostate Cancer Fund and GlaxoSmithKline.

Publications

Galm, U., Hager, M.H., vanLanen, S.G., Ju, J., Thorson, J.S., and Shen, B. (2005) Antitumor Antibiotics: Bleomycin, Enediynes, Mitomycin. Chem. Rev. 105: 739-758.

Singh, S., Hager, M.H., Zhang, C., Griffith, B.R., Lee, M., Hallenga, K., Markley, J.R., and Thorson, J.S. (2006) Structural insight into self-sacrifice mechanism of enediyne resistance. ACS Chem. Biol. 1 (7), 451- 460.

Hager, M.H., Solomon, K.R., and Freeman, M.R. (2006) The role of cholesterol in prostate cancer. Curr. Opin. Nutr. Metab. Care 9: 379-385.

Mukhopadhyay, N.K., Kim, J., Cinar, B., Ramachan, A., Hager, M.H., Adam, R.M., Raychaudruri, P., DeBenedetti, A., and Freeman, M.R. (2009) Heterogeneous Nuclear Ribonucleoprotein K is a Novel Regulator of Androgen Receptor Translation. Cancer Res. 69 (6): 2210-2218.

Di Vizio, D., Kim, J., Hager, M.H., Morello, M., Rubin, M.A., Adam, R.M., Yang, W., and Freeman, M.R. (2009) Oncosome Formation in Prostate Cancer: Association with a Region of Frequent Chromosomal Deletion in Metastatic Disease. Cancer Res. 69 (13): 5601-5609