DF/HCC Program Affiliation

Lung Cancer
Cancer Cell Biology

Research Abstract

Structural biology of tyrosine kinase signaling and cancer. We use x-ray crystallography and other biophysical and biochemical methods to study the structure and regulation of tyrosine kinases and their disregulation in cancer. Particular interests include EGFR kinase mutations in lung cancer and Jak kinase mutations in myeloproliferative disorders. We are also interested focal adhesion kinase, and in structure-based approaches to development of new tyrosine kinase inhibitors.

Publications

• Yun CH, Mengwasser KE, Toms AV, Woo MS, Greulich H, Wong KK, Meyerson M, Eck MJ.The T790M mutation in EGFR kinase causes drug resistance by increasing the affinity for ATP.Proc Natl Acad Sci U S A 2008 Jan 28.
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• Yun CH, Boggon TJ, Li Y, Woo MS, Greulich H, Meyerson M, Eck MJ.Structures of lung cancer-derived EGFR mutants and inhibitor complexes: mechanism of activation and insights into differential inhibitor sensitivity.Cancer Cell 2007 Mar;11(3):217-27.
  17349580
• Boggon TJ, Li Y, Manley PW, Eck MJ.Crystal structure of the Jak3 kinase domain in complex with a staurosporine analog.Blood 2005 Aug 1;106(3):996-1002.
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• Xu Y, Moseley JB, Sagot I, Poy F, Pellman D, Goode BL, Eck MJ.Crystal structures of a Formin Homology-2 domain reveal a tethered dimer architecture.Cell 2004 Mar 5;116(5):711-23.
  15006353
• Kim PW, Sun ZY, Blacklow SC, Wagner G, Eck MJ.A zinc clasp structure tethers Lck to T cell coreceptors CD4 and CD8.Science 2003 Sep 19;301(5640):1725-8.
  14500983
• Meng W, Sawasdikosol S, Burakoff SJ, Eck MJ.Structure of the amino-terminal domain of Cbl complexed to its binding site on ZAP-70 kinase.Nature 1999 Mar 4;398(6722):84-90.
  10078535
• Hof P, Pluskey S, Dhe-Paganon S, Eck MJ, Shoelson SE.Crystal structure of the tyrosine phosphatase SHP-2.Cell 1998 Feb 20;92(4):441-50.
  9491886
• Xu W, Harrison SC, Eck MJ.Three-dimensional structure of the tyrosine kinase c-Src.Nature 1997 Feb 13;385(6617):595-602.
  9024657