The driving force of Dr. Qin's project is due to advances in metallomics techniques and the development of copper trafficking theory; it is time to revisit the vascular function of copper, an essential nutrient in human.
Metallomics is a novel knowledge hub to connect the medicine with biology, chemistry, physics, and even geology. And the sensitivity and application of metallomic techniques have greatly improved. By working with Dr. Barry Lai at the Argonne National Laboratory, Dr. Qin's laboratory is beginning to utilize a highly novel approach, synchrotron radiation X-ray fluorescence microscopy (SRXRF) to investigate the spatial information of metal in the blood vessel wall. Application of SRXRF imaging to biological samples in early 21st century represented one of most exciting advances in metallomics. SRXRF, which can be used to detect small accumulations of copper in murine arterial walls and single microvascular cell, has enabled them to identify the preferential accumulation of copper in aortic elastic laminae.
Moreover, laser ablation inductively coupled plasma-mass spectrometry (LA-ICP-MS) is another novel metallomics imaging technique; its biological value in neuroscience has been demonstrated by Becker's group at the Central Division of Analytical Chemistry of the Research Center Juelich, Germany. Recently, Drs. Qin and Becker's labs acquired first metal distribution map using LA-ICP-MS in normal murine hearts. In addition, the emerging flow injection technique along with improved sample extraction methodology has produced a more powerful ICP-MS. The technique has been optimized and applied in Dr. Qin's project in vascular tissues and cells via a close collaboration with Dr. Joseph Caruso's group.
Copper trafficking in cells is a novel theory, which has been validated in several laboratories. This theory convincingly defines a group of proteins in the regulation of uptake, distribution, sequestration and export of cellular copper. Among these proteins, ATP7A has attracted significant attention since the identification of its function as a copper egress pump and the discovery of mutations of ATP7A leading to human Menkes disease. Dr. Qin's laboratory recently demonstrated that ATP7A is primarily localized in trans-Golgi apparatus in human primary macrophage. Human THP-1 cells are widely used as a macrophage model cell line, and a reasonable model to study copper metabolism. Dr. Qin's study revealed that PMA treatment leads to an increase in ATP7A expression and copper egress in THP-1 cells in a dose- and time-dependent fashion. PMA is a potent inducer of inflammation, angiogenesis, and cancer. These initial works lay out the foundation for the development of a novel concept, vascular metallomics, to bridge the gap between vascular biology and metallomics.
Thus, Dr. Qin's current research program includes the following two directions:
- Expression and function of copper transporter ATP7A in vasculature
- Vascular metallomics imaging