The Center for Diagnostics and Therapeutics is an interdisciplinary initiative to realize viable applications of research discoveries.
CDT on the Cover of Metallomics, June 2016
Metal ions play crucial roles in numerous biological processes, facilitating biochemical reactions by binding to various proteins. An increasing body of evidence suggests that neurotoxicity associated with exposure to nonessential metals (e.g., Pb2+) involves disruption of synaptic activity, and these observed effects are associated with the ability of Pb2+ to interfere with Zn2+ and Ca2+-dependent functions. However, the molecular mechanism behind Pb2+ toxicity remains a topic of debate. In this review, we first discuss potential neuronal Ca2+ binding protein (CaBP) targets for Pb2+ such as calmodulin (CaM), synaptotagmin, neuronal calcium sensor-1 (NCS-1), N-methyl-D-aspartate receptor (NMDAR) and family C of G-protein coupled receptors (cGPCRs), and their involvement in Ca2+-signalling pathways. We then compare metal binding properties between Ca2+ and Pb2+ to understand the structural implications of Pb2+ binding to CaBPs. Statistical and biophysical studies (e.g., NMR and fluorescence spectroscopy) of Pb2+ binding are discussed to investigate the molecular mechanism behind Pb2+ toxicity. These studies identify an opportunistic, allosteric binding of Pb2+ to CaM, which is distinct from ionic displacement. Together, these data suggest three potential modes of Pb2+ activity related to molecular and/or neural toxicity: (i) Pb2+ can occupy Ca2+-binding sites, inhibiting the activity of the protein by structural modulation, (ii) Pb2+ can mimic Ca2+ in the binding sites, falsely activating the protein and perturbing downstream activities, or (iii) Pb2+ can bind outside of the Ca2+-binding sites, resulting in the allosteric modulation of the protein activity. Moreover, the data further suggest that even low concentrations of Pb2+ can interfere at multiple points within the neuronal Ca2+ signalling pathways to cause neurotoxicity. Read More…
New Class of Protein Could Treat Cancer and Other Diseases, Georgia State Researchers Find
ATLANTA—A protein designed by researchers at Georgia State University can effectively target a cell surface receptor linked to a number of diseases, showing potential as a therapeutic treatment for an array of illnesses, including cancer, according to the research team.
ProAgio, which is created from a human protein, targets the cell surface receptor integrin αVβ₃ at a novel site that has not been targeted by other scientists. The researchers found ProAgio induces apoptosis, or programmed cell death, of cells that express integrin αVβ₃. This integrin has been a focus for drug development because abnormal expression of αVβ₃ is linked to the development and progression of a number of diseases.
The findings are reported in the journal Nature Communications.
“This integrin pair, αVβ₃, is not expressed in high levels in normal tissue,” said Zhi-Ren Liu, lead author of the study and professor in the Department of Biology at Georgia State. “In most cases, it’s associated with a number of different pathological conditions. Therefore, it constitutes a very good target for multiple disease treatment.” Read more…
Georgia State-Led Study Paves Way for New Therapies in Fight Against Calcium Disorders
ATLANTA—A study led by researchers at Georgia State University provides new insights into the molecular basis of human diseases resulting from mutations in the calcium-sensing receptor (CaSR), a protein found in cell membranes.
Their findings, published Friday (May 27) in the journal Science Advances, may assist in the development of novel receptor-based therapeutics for mutations that lead to certain types of hypocalcemia and neonatal hyperparathyroidism, in addition to Alzheimer’s disease and some cancers. Read More…
First Noninvasive Early Detection Of Liver Cancer Developed By Georgia State Researchers
ATLANTA—Led by Georgia State University, researchers have developed the first robust and noninvasive detection of early stage liver cancer and liver metastases, in addition to other liver diseases, such as cirrhosis and liver fibrosis.
Their findings were published Wednesday (May 13) in Proceedings of the National Academy of Sciences.
More than 700,000 people are diagnosed with liver cancer each year. It is the leading cause of cancer deaths worldwide, accounting for more than 600,000 deaths annually, according to the American Cancer Society. The rate of liver cancer in the U.S. has sharply increased because of several factors, including chronic alcohol abuse, obesity and insulin resistance.
Chemistry Ph.D. student Crystal Smitherman has received the Jeremy Knowles Travel Award at the 2015 Gordon Research Conference on Enzymes, Coenzymes, and Metabolic Pathways. Read more »
CDT members Drs. Aimin Liu and Zhiren Liu have just been named Distinguished University Professors of Chemistry and Biology, respectively. This is an honor reserved only for a small percentage of faculty for their extraordinary contributions to research, teaching, and service.
Dr. Jun Yin’s recent work on SUMO has made the back cover of ChemBioChem. Read more »
Dr. Aimin Liu’s study has been featured by the National Science Foundation on their new site, Science360 News. Read more »
Dr. Jenny Yang, CDT Associate Director, has been named a Distinguished University Professor by Georgia State University. Read more »
Center for Diagnostics and Therapeutics
Georgia State University
P.O. Box 5090
Atlanta, GA 30303-5090
Monica Liu is the Project Coordinator for The Center for Diagnostics and Therapeutics (CDT).