University of Miami >> Miller School of Medicine >> Office of Graduate Studies >> Faculty >> Faculty Detail

David J Robbins, Ph. D

305-243-5717 (office)

305-243-2810 (fax)

1042 RMSB, R104

drobbins@med.miami.edu


Curriculum Vitae

University of California, G.W. Hooper Foundation, CA

Post-doctoral research- 1998
 

University of Texas, Southwestern Medical Center, TX

PhD, Pharmacology- 1993
 

Rutgers University, NJ

BS, Biochemistry- 1987
 

Research Interests
The Hedgehog (Hh) signal transduction pathway plays a critical role in both early development and in cancer. Underscoring these observations, individuals with the developmental disorder known as Gorlin's syndrome, in which the Hh receptor is mutated, also exhibit an inherited predisposition to a variety of tumor types. Components of the Hh signaling pathway are also found mutated in sporadic forms of these same tumors. More recently, constitutive activation of the Hh pathway has also been implicated as a survival factor for a different subset of human tumors, including those derived from the lung, breast, prostate or pancreas. No mutations of Hh signaling components were found in these latter tumors. Rather, increased production of Hh was implicated as a key factor in tumor maintenance. Additionally, hyperactivation of the Hh signaling pathway was found to act as a marker of more aggressive tumors. Thus, the Hh pathway appears to play a crucial role in the progression and maintenance of many common tumors.
 
Consistent with the important role Hh plays in human cancer, recent results from the first clinical trial of a Hh small-molecule inhibitor showed a dramatic reduction in the tumor burden of patients who received this drug. The cellular target of this small-molecule is the G-protein coupled transmembrane protein Smoothened. While Smoothened plays a pivotal and rate limiting step in Hh signal transduction, the mechanism by which it acts remains largely unknown. My research program is focused on elucidating the role Hh plays in cancer, and toward this goal we have identified the only two known Smoothened effectors. Our future work is focused on: 1) dissecting the signaling pathway downstream of Smoothened, and 2) elucidating the production and presentation of the Hh ligand. We are studying this pathway in both developmental and pathological settings, making our research highly complementary and mutually supporting. Such an approach will more rapidly decipher the mechanism by which the Hh pathway contributes to human oncogenesis, as well as facilitate the rational design of additional Hh inhibitors.
 

Recent Publications
Fei DL, Li H, Kozul CD, Black KE, Singh S, Gosse JA, DiRenzo J, Martin KA, Wang B, Hamilton JW, Karagas MR, Robbins DJ: Activation of Hedgehog signaling by the environmental toxicant arsenic may contribute to the etiology of arsenic induced tumors. Cancer Research, 2010 1;70(5):1981-8.
 
Tokhunts R, Singh S, Chu T, D'Angelo G, Baubet V, Goetz JA, Huang Z, Yuan Z, Ascano M, Zavros Y, Therond PP, Kunes S, Dahmane N, Robbins DJ: The full-length unprocessed hedgehog protein is an active signaling molecule. J Biol Chem. 2010 285(4):2562-8.
 
Ogden SK, Fei DL, Schilling NS, Ahmed YF, Hwa J, Robbins DJ: “G Protein Galphai Functions Immediately Downstream of Smoothened in Hedgehog Signaling”. Nature. 18 456(7224):967-70; 2008.
 
Farzan SF, Ascano M Jr, Ogden SK, Sanial M, Brigui A, Plessis A, Robbins DJ: “Costal2 Functions As A Kinesin-like Protein In The Hedgehog Signal Transduction Pathway”: Curr Biol. 26 18(16):1215-20; 2008.
 

Robbins, D.J. and Hebrok, M. “Hedgehogs: La Dolce Vita”: EMBO Reports, 8, 451-455 2007.

Ma, Y., Fiering, S., Black, C., Liu, X., Yuan, Z., Memoli, V.A., Robbins, D.J., Tsongalis, G.J., Demidenko, E., Freemantle, S.J. and Dmitrovsky, E: “Transgenic Cyclin E Species Trigger Dysplasia And Multiple Pulmonary Adenocarcinomas”. Proc Natl Acad Sci ; 104(10): 4089-94; 2007.
 
Yuan, Z., Goetz, J. A., Singh, S., Ogden, S. A., Petty, W. J., Black, C. C., Memoli, V. A., Dmitrovsky, E., and Robbins, D. J.: “Frequent Requirement Of Hedgehog Signaling In Non-Small Cell Lung Carcinoma”. Oncogene ; 26:1046-55; 2007.
 

Zeng, X, Goetz, J., Suber, L., Schrenier, C., Scott, W., and Robbins, D.J.: “A Freely Diffusible Form Of Sonic Hedgehog Mediates Long-range Signaling”: Nature: 7, 411(6838): 716-20, 2001

 


 
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