Staff Profile: Damien Y. Duveau

Damien Y. Duveau, Ph.D., M.Sc.
Damien Y. Duveau, Ph.D., M.Sc.

Research Scientist, Chemistry Technology (Contractor)

Division of Pre-Clinical Innovation

National Center for Advancing Translational Sciences

National Institutes of Health

Email Damien Y. Duveau

Biography

Damien Duveau is a research scientist in the Chemistry Technology program within NCATS’ Division of Pre-Clinical Innovation (DPI). His research focuses on the design and synthesis of molecular probes and small molecules with druglike properties, aimed at studying novel targets and specific cellular signaling pathways. His work is carried out through hit-to-lead optimization, guided by structure-activity relationship studies. Since joining NCATS, Duveau has provided significant contributions to the development of small molecules targeting:

  • The myeloid cell leukemia 1 protein (Mcl-1), an antiapoptotic protein of the Bcl-2 family of proteins overexpressed in a number of cancers, such as multiple myeloma;
  • The O-linked β-N-acetylglucosamine transferase (OGT), a central enzyme involved in the post-translational modification of proteins;
  • The 15-hydroxyprostaglandin dehydrogenase (HPGD), an enzyme involved in the metabolism of prostaglandin E2; and
  • The integrin-associated protein CD47 (Cluster of Differentiation 47), a cellular receptor that plays a critical role in self-recognition. Numerous cancers exploit CD47 expression and its interaction with its natural ligand SIRP-α in order to evade immunological surveillance.

Before joining NCATS, Duveau was a postdoctoral research associate and then an assistant research scientist in the laboratory of Sidney Hecht, Ph.D., at the Biodesign Institute in the Center for BioEnergetics at Arizona State University, where he worked on the synthesis of geldanamycin and on the syntheses and characterization of multifunctional radical quenchers to study mitochondrial impairment diseases.

Duveau earned his M.Sc. degree in chemical engineering from the National Higher School of Chemistry (École Nationale Supérieure de Chimie de Montpellier) in France and his Ph.D. in chemistry from the University of Louisville. During his graduate studies, he worked in the laboratory of Frederick Luzzio, Ph.D., in collaboration with William Figg, Pharm.D., at the National Cancer Institute, on the synthesis of 5'-hydroxythalidomide to better understand the antiangiogenic properties of thalidomide.

Research Topics

Duveau is actively involved in the design and curation of the Mechanism Interrogation PlatE (MIPE), a library of approximately 2,500 bioactive agents annotated for their mechanisms of action and clinical development stages, with a focus on oncology. The MIPE library is regularly screened in a combinatorial and phenotypic format versus investigational or approved drugs to identify new additive or synergistic drug pairs. Such outcomes, coupled with mechanistic annotations, provide a better understanding of the molecular basis of diseases. In addition, such screening techniques may facilitate the discovery and advancement of new drug combinations toward the treatment of cancer, a key aspect of the developing field of precision medicine. Finally, Duveau is a member of the DPI working group charged with developing A Specialized Platform for Innovative Research Exploration (ASPIRE). The goal of the ASPIRE initiative is to automate chemical synthesis and integrate artificial intelligence and machine learning into the field of medicinal chemistry at NCATS.

Selected Publications

  1. Structure-Based Evolution of Low Nanomolar O-GlcNAc Transferase Inhibitors.
  2. Targeting neuronal activity-regulated neuroligin-3 dependency in high-grade glioma.
  3. Matrix Screen Identifies Synergistic Combination of PARP Inhibitors and Nicotinamide Phosphoribosyltransferase (NAMPT) Inhibitors in Ewing Sarcoma.
  4. Selective targeting of JAK/STAT signaling is potentiated by Bcl-xL blockade in IL-2-dependent adult T-cell leukemia.
  5. High-throughput combinatorial screening identifies drugs that cooperate with ibrutinib to kill activated B-cell-like diffuse large B-cell lymphoma cells.