Chemokine receptor signaling and function
Research in my laboratory focuses on functions of chemokines and chemokine receptors in primary and metastatic cancer. In particular, we are investigating independent and coordinated functions of chemokine CXCL12 (also known as SDF-1) and its two receptors, CXCR4 and CXCR7. These receptors are upregulated on malignant cells and tumor blood vessels in multiple malignancies, including breast and ovarian cancers, and CXCL12 also is secreted by stromal cells in primary and metastatic tumor microenvironments. Signaling through these receptors appears to regulate several steps in cancer initiation, progression, and metastasis.
To analyze these signaling pathways in cell-based assays and living mice, we utilize a wide variety of molecular imaging techniques ranging from intravital microscopy to whole animal imaging modalities. Through active collaborations with investigators in Biomedical Engineering (Dr. Shuichi Takayama) and Chemical Engineering (Dr. Jennifer Linderman), we develop novel microfluidic devices to study key steps in tumor progression under physiologic conditions in vitro and computational models to describe and predict signaling dynamics at multiple scales of biologic complexity. Our goals are to advance understanding of signaling pathways under physiologic conditions and gain new insights into mechanisms of metastasis that can be used to improve cancer therapy.
Shcherbo D, Shemiakina II, Ryabova AV, Luker KE, Schmidt BT, Souslova EA, Gorodnicheva TV, Strukova L, Shidlovskiy KM, Britanova OV, Zaraisky AG, Lukyanov KA, Loschenov VB, Luker GD, Chudakov DM. Near-infrared fluorescent proteins. Nat Methods. 2010; 7:827-9.
Torisawa YS, Mosadegh B, Bersano-Begey T, Steele JM, Luker KE, Luker GD, Takayama S. Microfluidic platform for chemotaxis in gradients formed by CXCL12 source-sink cells. Integr Biol (Camb). 2010 Nov 2; 2:680-6.
Ray P, Lewin SA, Mihalko LA, Schmidt BT, Luker KE, Luker GD. Noninvasive Imaging Reveals Inhibition of Ovarian Cancer by Targeting CXCL12-CXCR4. Neoplasia 2011;13:1152-1161.
Ray P, Lewin, SA, Mihalko LA, Lesher-Perez SC, Takayama S, Luker, KE, Luker GD. Secreted CXCL12 (SDF-1) Forms Dimers under Physiologic Conditions. Biochem J 2012; 442:433-42.
Luker KE, Mihalko LA, Schimidt BT, Lewin SA, Ray P, Shcherbo D, Chudakov DM, Luker GD. In Vivo Imaging of Ligand Receptor Binding with Gaussia Luciferase Complementation. Nat Med 2012; 18:172-177.
Luker KE, Lewin SA, Mihalko LA, Schmidt BT, Winkler JS, Thomas DG, Luker GD. Scavenging of CXCL12 by CXCR7 promotes tumor growth and metastasis of CXCR4-positive breast cancer cells. Oncogene 2012; Jan 23. doi: 10.1038/onc.2011.633. [Epub ahead of print]