Fundamental Understanding of Growth and Inhibition of Calcium Oxalate Kidney Stones

点击翻译按钮获取中文摘要

Non-Technical:Millions of Americans are afflicted by kidney stones and related diseases. Currently the sciences involved in the formation, composition and growth of kidney stones are not known. Hence, there are no well developed treatments, and how to prevent their formation and growth. Current treatments for the prevention of this disease using different inhibitors show inconsistent results among patients who often have similar symptoms. Calcium oxalate (CaOx) crystals are the main constituents of kidney stones. These crystals undergo nucleation and growth starting from atomic scale, and progresses to millimeter or centimeter scales. Most of the available therapeutic treatments are designed to address the presence of crystals that may be detected through standard imaging techniques. At this stage of the crystal growth, these crystals become very stable and are difficult to breakdown or dissolve. The proposed research aims to understand the sciences involved in the nucleation and growth of crystals with the goal to understand the chemical and physical changes to these crystals at nanoscales. Understanding the nanoscale crystallization of CaOx, and the mechanisms through which different crystal structures are formed could provide clues why some medications are effective in treating only some kidney stone patients. The proposed advanced microscopic studies could provide insight into kidney stone formation and growth, and sciences from these studies could in turn develop novel prevention and treatment protocols, if this research is successful. Additionally, these materials research studies would be invaluable in other sciences for which crystal formation and growth are critical, such as polymers, pharmaceuticals, food products, geosciences and electro optic materials. Through the course of this research, particular attention will be given in recruiting and mentoring female and underrepresented students to work in the principal investigators' research laboratory. In addition, the research findings of this project will be incorporated in relevant undergraduate and graduate classes to further stimulate a new generation of students with the fundamental knowledge to engage in this field. To increase public awareness, the PIs plans to disseminate the new results of this project through social media, press coverage, and news releases.Technical:The goal of this project is to gain a better understanding of the basic sciences in the formation mechanisms of calcium oxalate (CaOx) minerals that are responsible for kidney stone disease. This disease affects approximately 20 million people in the United States. The current treatments show inconsistent results for these patients indicating that more fundamental understanding must be gained on how these crystals formed and how one can prevent the growth of such minerals. Using liquid electron microscopy with subnanometer scale resolution, this program will study the formation of calcium oxalate crystals in liquid solution. A unique advantage of this study is the ability to monitor the local chemical and structural evolutions with the state-of-the art aberration-corrected transmission electron microscopy equipped with imaging and spectrometers sensitive to single atoms. The proposed research is expected to yield a new understanding on the growth kinetics of Calcium crystals under different environmental conditions. The scientific broader impact of these studies could benefit further understanding in crystal formation and growth of polymers, pharmaceuticals, food products, geosciences and electro optic materials. The broader impacts with respect to outreach activities of this award would be the inclusion of students at both undergraduate and graduate level in training and education on the state-of-the art microscopy techniques for health sciences in improving the quality of life. As part of the planned outreach activities, minority and underrepresented students will be included for scientific visits and hands-on experience in the lab activities. The finding of this research will be incorporated in a bioengineering graduate course that has been developed for senior undergraduate and graduate students. The PIs are committed to recruit female/minority students for undergraduate education through well-established outreach programs at the University of Illinois at Chicago.