Research Projects

Chemokines are small signaling proteins secreted by cells of the immune system. They affect the migratory pattern and positioning of immune cells and are required for health. The receptors that respond to chemokine gradients, known as chemokine receptors, are classically expressed by white blood cells, however, these receptors become deregulated in cancer. Healthy cells at distant sites can secrete chemokines that attract the cancer cells overexpressing chemokine receptors in the process known as metastasis. Aberrant chemokine receptor expression supports tumor growth, altering the microenvironment of the tumor and providing cancer cells a survival advantage. Targeting chemokine receptors and disrupting their interaction with associated proteins may result in improved treatment efficacy for cancer and many other inflammation-related diseases.

**Chemokine receptors:** These receptors are members of the 7-transmembrane guanine nucleotide-binding protein (G protein)–coupled receptor super family. In general, upon binding to their ligands, chemokine receptors undergo conformational changes that allow the binding of G proteins to intracellular loop epitopes and the carboxyl terminal tail of the receptors. The chemokine receptors that do not bind G proteins may act in synchrony with other proteins such as b-arrestin, integrins, and growth factor receptors to support their downstream effects. Crit Rev Eukaryot Gene Expr. 2013; 23(1): 77–91.

Project One- identifying tumor-cell markers to assess their interactions with cancer cells:

Expression profiling shows altered profiles in non cancer cells within the microenvironment, revealing that these specialized types of cell, although not cancer originally, are integral to cancer progression. We are identifying signatures in these cell types to determine whether how we can target their interactions with cancer cells.

Project Two– Analyzing the relationship of antibody structure with function:

Antibodies and FC-fusion proteins are at the forefront of biomedical research as some of the best treatments available for many cancers and inflammatory disease. Antibodies activate innate immune processes including antibody dependent cellular cytotoxicity and antibody dependent cellular phagocytosis.

Monoclonal antibodies may also induce complement-dependent cytotoxicity and inhibition of survival signals to trigger apoptosis; and due to their evolution-optimized properties, they are biologically active in vivo longer than small molecules. Antibodies depend heavily on the glycan (sugar chain) modifications of their FC-(Fragment crystallizable) region to exert their properties. In this project we will classify, phenotypically and structurally, the modifications that enhance the anti-tumor activity of the parent antibody against chemokine receptors.

Our research has been supported by:

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