CLEAR/CURES Research Seminar: Dr. Andrew Lipchik (Wayne State U) - October 23, 2025

ABSTRACT
Heavy metals, including arsenic, cadmium, lead, mercury, and chromium, are among the most concerning chemicals to public health. Metal chelation therapy (MCT) is the primary treatment for heavy metal toxicity and exposure. This requires the administration of small organic molecules to remove the toxic metal of interest. However, current MCT suffers from several limitations, including poor pharmacokinetics and the inability to distinguish between the toxic metal of interest and essential metals. These limitations combine to result in inefficient removal of toxic metals and disruption of metal homeostasis. Therefore, the development of new metal chelators that are specific to the target metal is necessary for treating heavy metal exposure and toxicity. Ideally, chelating agents should have aqueous solubility, high affinity for the target metal, high specificity, the ability to cross tissues and cell membranes, low toxicity, and the ability to eliminate the metal-bound complex. Peptides can achieve all these criteria. Recently, we have identified peptide chelators with specificity for cadmium (Cd) and lead (Pb). Here, we present the characterization of Cd and Pb binding to these peptides using biochemical, biophysical, and analytical methods to determine the contribution of each amino acid in these peptides to metal binding. Utilizing these mechanisms of binding, we have optimized the binding properties and stability of these peptides to their respective metals, improving the binding affinity by as much as 100-fold. The improvement in stability and binding has translated to improved rescues of a number of phenotypes, including viability, redox stress, and iron mobilization in vitro. These results demonstrate the potential of these peptide chelators for the treatment of Cd and Pb toxicity.

ABOUT THE SPEAKER
Dr. Andrew Lipchik received his doctoral degree from Purdue University in the Department of Medicinal Chemistry and Molecular Pharmacology in 2013 in the laboratory of Dr. Laurie Parker. His thesis work focused on the development of novel peptide biosensors for detection of kinase activity utilizing terbium coordination and luminescence. Following his graduate work, he joined the laboratory of Dr. Michael Snyder at Stanford University as a NIH Ruth L. Kirschstein Postdoctoral Fellow, where he focused on regulation of histone synthesis and therapeutic targeting of this pathway. Dr. Lipchik is now an assistant professor at Wayne State University in the Department of Pharmaceutical Sciences were he is integrating his training in peptide chemistry, metal coordination chemistry, and genetics to develop new chelators as well as understanding of biochemical underpinnings of their toxicity.

ABOUT CLEAR
CLEAR is funded by the National Institute of Environmental Health Sciences of the National Institutes of Health (NIH) Superfund Research Program (SRP). The center is dedicated to understanding and mitigating adverse birth outcomes and serious developmental health problems that have been associated with urban environmental exposure to volatile organic chemicals or VOCs, a special class of pollutants found in the subsurface of post-industrial cities like Detroit MI. Sadly, Detroit has the highest preterm birth rate in the country (15.2%), and up to 37 of the 67 Superfund sites in Michigan must manage VOC contamination. Watch this video to learn more and subscribe to our channel. Check out our website www.clear.wayne.edu, or follow us on X at www.x.com/CLEARWSU.