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Xiaolin He, PhDAssistant Professor
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Our lab is interested in the structural mechanisms governing the transmembrane signaling events that are critically important in the genesis and development of cancer. Our primary efforts are trying to grasp atomic pictures how the transmembrane receptors recognize their ligands, and how these recognition/activation processes are implicated in cancer. We are also extending into the intracellular signaling cascades of these receptors, particularly the interaction between the receptor cytoplasmic part and the adaptor/regulator proteins. We will use high-resolution X-ray crystallography in combination with other biochemical and biophysical methods to address the biological questions.
Our current research topics mainly include receptor tyrosine kinases and neural receptors. Receptor tyrosine kinases play vital roles in cell growth and differentiation and are frequently involved in cancer, but how their ligands recognize their extracellular domains and activate their intrinsic catalytic activities are not completely understood for most of the family members. Deciphering these schemes is important in designing cancer drugs targeting at transmembrane signaling. We are trying to solve high-resolution structures of various receptor/ligand complexes of this family, such as VEGF/VEGF-Rs, kit/SCF, fms/MCSF, Flt3/Flt3L, and Tie2/Angiopoietins, which are implicated in a variety of cancer types including breast cancer, leukemia, and GIST.
Neurobiology is a rapidly developing field, and offers exciting opportunities for unraveling novel receptor/ligand interations. We are trying to understand the structural mechanisms used by the neuronal receptors in the signaling and regulation of the proliferation, differentiation and growth inhibition of nerve cells. We are working on the neurotrophin receptors (p75, Trk) and the axon guidance receptors (semaphorin/plexin, Robo/Slit, etc.).
He, X.L., Bazan, J.F., McDermott, G. Park, J.B., Wang, K., Tessier-Lavigne, M., He, Z. and Garcia, K.C. Structure of the Nogo receptor ectodomain: a recognition module implicated in myelin inhibition. Neuron 2003, 38: 177-185.
He, X.L., Garcia, K.C. Structure of nerve growth factor complexed with the shared neurotrophin receptor p75. Science, 2004, 304(5672):870-5.
He X.L., Dukkipati A., Wang X., Garcia K.C. A new paradigm for hormone recognition and allosteric receptor activation revealed from structural studies of NPR-C.
Peptides. 2005;26(6):1035-43.
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View Publications by Xiaolin He listed in the National Library of Medicine (PubMed). |
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