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Gerard Blobe

Associate Professor
Pharmacology and Cancer Biology
(919) 668-1352
Research Interest: 
Cell cycle
Cell biophysics
Signal transduction
Research Summary: 
The role of transforming growth factor-beta (TGF-beta) superfamily signaling pathways in cancer biology.
Research Description: 

Our laboratory focuses on the role of transforming growth factor-beta (TGF-beta) superfamily signaling pathways in cancer biology. The TGF-beta signaling pathway functions as both a tumor-suppressor and as tumor promoter during carcinogenesis. This dichotomy of TGF-beta function remains a fundamental problem in the field both in terms of understanding the mechanism of action of the TGF-beta pathway, and directly impacting our ability to target this pathway for the chemoprevention or treatment of human cancers. Resistance to the tumor suppressor effects of TGF-beta is also a common feature of epithelial-derived human cancers, however, mechanisms for TGF-beta resistance remain undefined in the majority of cases. The laboratory is currently focused on elucidating mechanisms for TGF-beta resistance and for the dichotomous function of TGF-beta in human breast, colon, pancreatic and renal cell cancers using a multidisciplinary approach. TGF-beta and the TGF-beta signaling pathway also have an important role in vascular biology. Indeed, mutations in two endothelial specific TGF-beta receptors, endoglin and ALK-1, are responsible for the human vascular disease, hereditary hemorrhagic telangiectasia (HHT), and mice which lack expression of these receptors are embryonic lethal due to defects in angiogenesis. Studies are currently underway to elucidate the signal transduction pathway downstream from these receptors and to establish their role in regulating tumor-induced angiogenesis. The ultimate goal of these studies is the ability to target the TGF-beta pathway for the chemoprevention or treatment of human cancers.

Beta-arrestin 2 mediates endocytosis of type III TGF-beta receptor and down-regulation of its signaling.
Chen W, Kirkbride KC, How T, Nelson CD, Mo J, Frederick JP, Wang XF, Lefkowitz RJ, Blobe GC.
Science. 2003. 301:1394-7.

The type III TGF-beta receptor suppresses breast cancer progression.
Dong M, How T, Kirkbride KC, Gordon KJ, Lee JD, Hempel N, Kelly P, Moeller BJ, Marks JR, Blobe GC.
J Clin Invest. 2007. 117:206-17.

Bone morphogenetic proteins signal through the transforming growth factor-beta type III receptor.
Kirkbride KC, Townsend TA, Bruinsma MW, Barnett JV, Blobe GC.
J Biol Chem. 2008. 283:7628-37.

The type III TGF-beta receptor regulates epithelial and cancer cell migration through beta-arrestin2-mediated activation of Cdc42.
Mythreye K, Blobe GC.
Proc Natl Acad Sci U S A. 2009. 106:8221-6.

Mechanical stiffness grades metastatic potential in patient tumor cells and in cancer cell lines.
Swaminathan V, Mythreye K, O'Brien ET, Berchuck A, Blobe GC, Superfine R.
Cancer Res. 2011. 71:5075-80.