Anton Simeonov, Ph.D., is the acting deputy director of NCATS in the center’s Office of the Director. Simeonov plans, conducts and assesses the center’s complex preclinical and clinical research programs and serves as a key national spokesperson for translational science. He guides the activities of the NCATS Advisory Council and the Cures Acceleration Network Review Board. Simeonov also is the director of the Chemical Genomics Branch within NCATS’ Division of Preclinical Innovation. The goal of the Chemical Genomics Branch is to explore new technological and operational concepts. Such concepts range from strategies for drug discovery and testing to improving the use of stem cells in research. Previously, Simeonov served as the center’s scientific director from August 2015 to January 2024.
Simeonov is the author of more than 250 peer-reviewed scientific publications and an inventor on many patents. He has a diverse background that spans from bioorganic chemistry and molecular biology to clinical diagnostic research and development. He earned a Ph.D. in bioorganic chemistry from the University of Southern California and a B.A. in chemistry from Concordia College. Simeonov trained as a postdoctoral fellow at the Scripps Research Institute under Richard Lerner, M.D., and Kim Janda, Ph.D.
Prior to joining NIH in 2004, Simeonov was a senior scientist at Caliper Life Sciences, where he performed basic research on novel assay methodologies and the development of microfluidic products for research and clinical diagnostics. For the past two decades, Simeonov has served in journal editorial roles, and in 2018, he co-chaired the annual conference of the Society of Laboratory Automation and Screening.
Simeonov’s research interests include novel detection chemistries and techniques, assays and devices for diagnostics, assay miniaturization, and novel approaches to screening and therapeutics development. Presently, Simeonov and his group focus on developing assays to find and identify small-molecule modulators of previously understudied molecular targets and pathways. The goal is to de-risk these novel targets through the development of assay methodology and high-quality pharmacological tool compounds. Watch a video about NCATS laboratories to learn more.
To expand the collection of therapeutic modalities at NCATS, Simeonov began research in the field of antibody discovery and development by generating synthetic, humanized, llama-based nanobody libraries. They were completed during the peak of the COVID-19 pandemic. In this unprecedented public health emergency, Simeonov and his group pivoted to employ these new libraries in phage-panning protocols against the receptor binding domain (RBD) of the SARS-CoV-2 spike protein. One of the nanobodies discovered, RBD-1-2G, possessed a high binding affinity and was able to directly compete with ACE2 binding to the RBD region. The team’s first antibody discovery was published in 2022. In April 2022, NIH contributed the intellectual property around the nanobody library and anti-spike nanobody technology to the technology pool organized by The White House and the World Health Organization to enable royalty-free access to anti-COVID therapies by developing countries. Building on the success of the SARS-CoV-2 project, Simeonov’s group recently established several antibody discovery collaborations.
Simeonov’s current projects include the following:
- Antibody discovery, nanobody libraries
- Epigenetic targets, specifically histone demethylases and acetyltransferases
- DNA repair proteins
- Imaging and 3-D-based assays to discover novel antivirals
- Metabolic enzymes as targets in oncology
- Lipoxygenases and related lipid-modifying enzymes, ferroptosis
- Redesigning existing assays to minimize the interfering effect of library compounds
- Novel approaches to demonstrating small-molecule target engagement in the cell
- Library profiling to enable generation of artificial intelligence/machine learning predictions