Irina Nesmelova, PhD, assistant professor in UNC Charlotte’s Department of Physics and Optical Sciences, studies the effect of protein heterodimer formation on the biological activity of a family of cytokines that guide the migration of leukocytes during normal and inflammatory conditions. By understanding the change in biological activity that results from the formation of heterodimers, she is investigating the link between controlling chemokine activity and chronic diseases like cancer.
Working with scientists at the David H. Murdock Research Institute (DHMRI) and Associate Professor Didier Dréau, PhD, in the UNC Charlotte’s Department of Biological Sciences, 11 chemokines were analyzed using a ThermoOrbitrap ™ mass spectrometer with a nanoelectrospray ionization source. The method determined which chemokines most preferentially form heterodimers among an assortment of platelet-derived chemokines.
“We particularly focused on two chemokines CXCL7 and CXCL4,” Nesmelova said. “These are the most abundant chemokines released from platelets in high concentrations. We looked at all 11 chemokines and their interaction with these two, and we identified complexes that form strong heterodimers.”
They observed strong heterodimerization between CXCL12 and CXCL4 or CXCL7. Nesmelova and Dréau also found that CXCL4 interacted with CXCL12. “CXCL12 actually promotes breast cancer cell migration, and CXCL4 interacts with it to blocks its migration,” Nesmelova explained.
The preliminary data gained through the use of DHMRI’s mass spectrometry contributed to a National Institutes of Health grant application to further study CXCL4 and CXCL12, screen additional chemokines and conduct NMR experiments to build a structural model, which will assist in the design of a peptide to regulate the activity of these chemokines and breast cancer cell migration.
“I am not a specialist in mass spectrometry so DHMRI ran the experiments, and I analyzed the data,” Nesmelova said. “I find DHMRI to be a great resource. The equipment is excellent, and everyone is very helpful and able to discuss how to design the best experiments.”
The results were published in the paper “The heterodimerization of platelet-derived chemokines” that was printed in the journal Biochimica et Biophysica Acta (BBA), co-authored by Nesmelova, Dréau and DHMRI scientists.