Microbiology, Immunology & Molecular Genetics Adjunct Faculty
Andrew Hayhurst, Ph.D.
Virology & Immunology
Dr. Hayhurst's laboratory mainly engineers single domain antibodies (sdAb) as rugged recognition motifs for biological threats including high consequence pathogens and toxins such as Filoviruses and botulinum neurotoxins. The sdAb are particularly useful for resource-poor environments since they are very heat stable and can quantitatively refold after melting. Dr. Hayhurst's own graduate training in Virology, and post-doctoral training in antibody engineering enables him to combine strengths to engineer these sdAb for a variety of purposes including rugged diagnostics and novel therapeutics for emerging threats. Dr. Hayhurst's interest in cancer leans on his expertise to engineer bacteria to display anti-CEA scFv and modulate the surface of bacteriophage to enhance tumor targeting and therapeutic options. These and other studies lead Dr. Hayhurst to secure R21 and R01 funding used to support graduate trainees. His expertise in developing sdAb as rugged immunoassay reagents and producing high quantities of quality material suitable for even crystallization studies help the lab explore the mechanism of how the antibodies bind antigens of interest. Therefore, the lab provides an applied research environment with a basic core of wanting to understand how things work that gives graduate students training in translational science, critical thinking and problem solving skills.
Ph.D., Molecular Virology at the National Institute for Medical Research, England
Keywords: Antibody Engineering; Filovirus; Single Domain Antibodies (sdAb)
Dr. Hayhurst's laboratory has a variety of interests mostly related to antibody engineering technology and applications to emerging pathogen countermeasures, tumor targeting and nanotechnology. His lab has recently developed a simple yet effective route to transition from large antibody repertoires to individual sandwich assays in a single day without the need for protein purification or modification to accelerate the antibody characterization process. The rapid antibody pipeline was used to formulate an anti-botulinum neurotoxin assay from an immune repertoire and an anti-Zaire Ebolavirus assay from a non-immune library within the BSL4 lab. They continue to explore the molecular basis for antigen recognition by llama single domain antibodies with their collaborators Alex Taylor and John Hart (UTHSCSA) to rationalize why their antibodies are so effective at recognizing Filovirus nucleoprotein C-termini thereby enabling monoclonal affinity reagent sandwich assays to function so well. As part of this work they are developing a high throughput system to deconvolute the amino-acid residues within both antigen and antibody that are critical for recognition to complement the structural approach and help when antibody-antigen complexes prove fickle to crystallize. They are aiming to disrupt the Filoviral replication machinery using single domain antibodies as intrabodies since they can be potent inhibitors of specific roles of multi-functional proteins and enable one to break down individual contributions to the viral life cycle as opposed to siRNA knockdown style experiments. Dr. Hayhurst's lab tumor targeting work involves modifying bacterial surfaces to more homogenously target tumors rather than just necrotic cores in order to enhance the likelihood of complete tumor regression following bacterial based therapies. Their interests in nanotechnology center on an unusual protein format that appears to rapidly stimulate the promiscuous formation of macromolecular crystalline aggregates of several salts that are visible to the naked eye and we hope to rationalize the mechanism of this phenomenon.
Awards & Accomplishments
- 2004 – San Antonio Business Journal “40 under 40” award
- 2007 – Naval Research Laboratory Alan Berman award for outstanding research publication, Facile generation of heat stable antiviral and antitoxin single domain antibodies from a semisynthetic llama library
- 2007 – NIH U01 Reviewer ZAI1-TP-M-J2, RFA-AI-07-003: Cooperative Research Partnerships in Biodefense
- 2008 – NIH U01 Reviewer ZAI-1-3 (diagnostics) and ZAI-1-1 (immunotherapeutics), RFA-AI-08-001: Cooperative Research Partnerships in Biodefense
- 2009 – NIH P01 Reviewer, ZAI1 GPJ-M(S1): Novel Diagnostics and Therapeutics for Caliciviruses
- 2009 – NIH Challenge Grant Reviewer ZRG1 IMM-E(58)R
- 2010 – NIH R01 Reviewer ZAI1 FDS-M M2 1, RFA-AI-09-028: Partnerships for Biodefense Viral Pathogens
- 2011 - USPO# US7,871,796 “Isolation of binding proteins with high affinity to ligands”. UT Regents
- 2013 - NIH R03 Reviewer ZRG1 BST-F (55) R: Indo-US collaboration on low cost medical devices
- Present - Patent Pending, USPO#US 61/514,717 “Nucleic Acid Compositions, Methods and Kits for Rapid Ligand Pairing”. Texas Biomedical Research Institute
- 2005 – present American Society for Microbiology
- 2005 – present American Society for Virology
- 2007 – present American Chemical Society
Goldman ER, Anderson GP, Liu JL, Delehanty JB, Sherwood LJ, Osborn LE, Cummins LB, Hayhurst A. Facile generation of heat stable antiviral and antitoxin single domain antibodies from a semisynthetic llama library. Anal Chem 2006; 78:8245-8255.
Sherwood LJ, Osborn LE, Carrion R Jr, Patterson JL, Hayhurst A. Rapid assembly of sensitive antigen capture assays specific for Marburg virus using phage display panning at biosafety level four. J Infect Dis 2007; 196(suppl 2):S213-S219.
Goldman ER, Anderson GP, Conway J, Sherwood LJ, Fech M, Vo B-H, Liu JL, Hayhurst A. Thermostable llama single domain antibodies for detection of botulinum neurotoxin A complex. Anal Chem 2008; 80(22):8583-8591. PMCID: PMC2829253
Conway J, Sherwood LJ, Collazo MT, Garza JA, Hayhurst A. Llama single domain antibodies specific for the 7 serotypes of botulinum neurotoxin as heptaplex immunoreagents. PLoS ONE 2010; 5(1):e8818. PMCID: PMC2809108
Swain MD, Anderson, GP, Zabetakis D, Bernstein RD, Liu JL, Sherwood LJ, Hayhurst A, Goldman ER. Llama-derived single domain antibodies for the detection of botulinum A neurotoxin. Anal Bional Chem 2010; 398(1):339-348. PMCID: PMC3049303
Kalarical Janardhanan S, Narayan S, Abbineni G, Hayhurst A, Mao C. Architectonics of phage-liposome nanowebs as optimized photosensitizer vehicles for photodynamic cancer therapy. Mol Cancer Ther 2010; 9(9):2524-2535. PMCID: PMC2937092
Wu M, Park YJ, Pardon E, Turley S, Hayhurst A, Deng J, Steyaert J, Hol, W.G. Structures of a key interaction protein from the Trypanosoma brucei editosome in complex with single domain antibodies. J Struct Biol 2011; 174(1):124-136. PMCID: PMC3037447
Hayhurst, A. Re: “Neutralizing human antibodies binding multiple serotypes of botulinum neurotoxin” by Garcia-Rodriguez et al., PEDS 2011; 24:321-331. Protein Eng Des Sel 2011; 24(9):633.
Sherwood, L.J., Hayhurst, A. Hapten mediated display and pairing of recombinant antibodies accelerates assay assembly for biothreat countermeasures. Sci Rep 2012; 2: 807. PMCID: PMC3495282
- Sherwood, L.J., Hayhurst, A. Ebolavirus nucleoprotein C-termini potently attract single domain antibodies enabling monoclonal affinity reagent sandwich assay (MARSA) formulation. PLoS ONE 2013; 8(4): e61232. PMCID: PMC3618483