Biography

Dehua Pei received his B.S. in Chemistry from Wuhan University and his Ph.D. in Organic Chemistry from the University of California, Berkeley. Following a postdoctoral fellowship at Harvard Medical School, he joined the faculty at The Ohio State University in 1995. Dr. Pei is a Fellow of the American Association for the Advancement of Science (AAAS) and the National Academy of Inventors (NAI). He is a co-founder of multiple biotechnology companies, including Entrada Therapeutics (NASDAQ: TRDA).

Research Overview

Biochemistry | Chemical Biology | Organic Chemistry

Approximately 75% of disease-relevant human proteins are considered "undruggable" by conventional modalities like small molecules (< 500 Da) or standard biologics (> 5000 Da). These targets primarily involve intracellular protein-protein interactions (PPIs) or missing/defective proteins caused by genetic mutations.

Our group seeks to solve the fundamental challenge of cellular delivery: how to transport large, functional biomolecules across the cell membrane. By discovering fundamental membrane translocation pathways, we engineer novel delivery platforms—cyclic cell-penetrating peptides (CPPs) and membrane translocation domains (MTDs)—to pioneer a new class of intracellular biologics for previously intractable diseases.

Current Research Thrusts

• Elucidating Membrane Translocation Mechanics (VBC Pathway)

While the cell membrane restricts most large biomolecules, bacterial toxins, non-enveloped viruses, and certain proteins cross it naturally. We discovered the Vesicle Budding-and-Collapse (VBC) mechanism—a fundamental pathway driving the cytosolic entry of cyclic CPPs and toxins. Current work investigates VBC involvement in non-enveloped viral entry, lipid nanoparticle (LNP) dynamics, and unconventional protein secretion in eukaryotes.

• Engineering Delivery Vehicles: Cyclic CPPs & MTDs

  Leveraging VBC mechanics, we design autonomous delivery systems that drive efficient endosomal escape:

  • Cyclic CPPs: Ideal for chemical conjugation to synthetic peptides, oligonucleotides, and small-molecule payloads.
  • Membrane Translocation Domains (MTDs): Small (~90 aa) protein domains that can be genetically fused to the N- or C-terminus of cargo proteins (or RNPs) for single-step recombinant production in E. coli or eukaryotic hosts.

• Developing Intracellular Biologics & Chemical Probes

  We apply our delivery platforms across diverse therapeutic and biotechnological spaces:

  • PPI Inhibitors: Conjugating cyclic CPPs to macrocyclic peptides to target previously intractable intracellular protein interfaces.
  • Protein & RNP Therapeutics: Delivering MTD-fused enzymes, antibodies, and genome-editing complexes into mammalian and plant cells to replace missing proteins, modulate gene expression, or execute targeted genome editing.

Selected Publications

Wang, J., Patel, P., Bhat, P., Hu, C., Storch, C., Harty, B., Bellizzi, M., Jordan, C., Good, D., Gopalan, V., Jacobs, J. M., Pei, D., and Wang, G.-L. (2026) Systemic Delivery of Functional Proteins into Plants Using an Engineered Membrane Translocation Domain. Plant Biotechnol. J. 24, 3939–3952.

Bhat, P., Salim, H., Ritchey, J. L., Li, N., Harty, B. B., Patel, T., Zhao, J., Wang, Q.-E., King, V. L., Tartaglia, L., Gyuris, J., and Pei, D. (2026) Intracellular Delivery of Peptides and Proteins with an Engineered Membrane Translocation Domain. ACS Chem. Biol. 21, 1818–1828.

Mandal, S., Ritchey, J. L., Bhat, P., and Pei, D. (2026) Discovery of a Minimally Charged Cell-Penetrating Peptide. Biochemistry 65, 985–993.

Pei, D. (2025) Endosomal Escape of Lipid Nanoparticles: A Perspective on the Literature Data. ACS Nano 19, 40293–40303.

Ritchey, J. L., Filippi, L., Ballard, D., and Pei, D. (2024) Bismuth-Cyclized Cell-Penetrating Peptides. Mol. Pharmaceutics 21, 5255–5260.

Sahni, A., Ritchey, J. L., Qian, Z., and Pei, D. (2024) Cell-Penetrating Peptides Translocate across the Plasma Membrane by Inducing Vesicle Budding and Collapse. J. Am. Chem. Soc. 146, 25371–25382.

Pei, D. (2022) How Do Biomolecules Cross the Cell Membrane? Acc. Chem. Res. 55, 309–318.

Sahni, A., and Pei, D. (2021) Bacterial Toxins Escape the Endosome by Inducing Vesicle Budding and Collapse. ACS Chem. Biol. 16, 2415–2422.

Buyanova, M., Cai, S., Cooper, J., Rhodes, C., Salim, H., Sahni, A., Upadhyaya, P., Yang, R., Sarkar, A., Li, N., Wang, Q. E., and Pei, D. (2021) Discovery of a Bicyclic Peptidyl Pan-Ras Inhibitor. J. Med. Chem. 64, 13038–13053.