Aaron LeBeau, PhD

Biography

Research Interests

• Single-domain antibody engineering
• Targeted radionuclide therapy and nuclear imaging
• Antibody-drug conjugates
• Strucutral biology

The LeBeau laboratory operates at the interface of synthetic biology and nuclear medicine. Our goal is to decrease cancer mortality and morbidity by developing antibody‑based molecular imaging agents and targeted therapeutics. We are pioneering the use of Variable New Antigen Receptors (VNARs) isolated from shark antibodies as targeting vectors in models of human cancer. All of our VNARs are generated in-house through the direct immunization of nurse sharks. VNARs are a fraction the size of human antibodies and possess a high degree of molecular dexterity. This allows us to engineer VNARs onto different scaffolds to create multivalent, bispecific, or biparatopic constructs for enhanced targeting. Our research has been featured by multiple national and international media outlets ranging from the BBC to NPR’s Radiolab.

Selected Publications

• Ubah OC, Lake EW, Ott KL, Priyanka S, Celeda S, West JL, Gunaratne GS, Shi K, Moeller NH, Porter AJ, Aihara H, Kosoff D, LeBeau AM, Barelle CJ. “The structural basis for the selective antagonism of soluble TNF-alpha by shark variable new antigen receptors.” Nature Communications. 2025 Nov 29;17(1):256.
• Gunaratne GS, Gallant JP, Ott KL, Broome PL, Celada S, West JL, Mixdorf JC, Aluicio-Sarduy E, Engle JW, Boros E, Meimetis L, Lang JM, Zhao SG, Hernandez R, Kosoff D, LeBeau AM. The characterization of variable new antigen receptors targeting FAP isolated from a novel immunized library. Communications Biology. 2025 Aug 13;8(1):1210.
• Gallant JP, Hintz HM, Gunaratne GS, Breneman MT, Recchia EE, West JL, Ott KL, Heninger E, Jackson AE, Luo NY, Rosenkrans ZT, Hernandez R, Zhao SG, Lang JM, Meimetis L, Kosoff D, LeBeau AM. Mechanistic Characterization of Cancer-associated Fibroblast Depletion via an Antibody-Drug Conjugate Targeting Fibroblast Activation Protein. Cancer Research Communications. 2024 Jun 12;4(6):1481-1494.
• Ubah OC, Lake EW, Gunaratne GS, Gallant JP, Fernie M, Robertson AJ, Marchant JS, Bold TD, Langlois RA, Matchett WE, Thiede JM, Shi K, Yin L, Moeller NH, Banerjee S, Ferguson L, Kovaleva M, Porter AJ, Aihara H, LeBeau AM, Barelle CJ. Mechanisms of SARS-CoV-2 neutralization by shark variable new antigen receptors elucidated through X-ray crystallography. Nature Communications. 2021 Dec 16;12(1):7325.