B.Sc. Genetics (hons, first class), University of Aberdeen, UK.

M.Sc. Antibody Engineering (with distinction), University of Aberdeen, UK. 

Ph.D. ‘Characterisation of single domain antibody fragments from the Nurse Shark, Ginglymostoma cirratum, using phage display’, University of Aberdeen, UK.

Associate Fellow of the Higher Education Academy (HEA), UK.

After completing my PhD in antibody engineering at the University of Aberdeen I moved to the US to join the comparative immunology group of Dr Martin Flajnik at the University of Maryland School of Medicine, as a post-doc. It was there that I became interested in understanding the evolution of the immune system and began to study the immune molecules and responses of sharks. We were the first team to show that libraries of highly stable, target-specific binding-domains ('VNARs', derived from the novel antibody isotype IgNAR), could be generated from immunized sharks. This technology was licensed by the pharmaceutical company Wyeth and in 2008 I was recruited as a Principal Research Scientist in their Global Biotherapeutics Technologies division, heading one of the teams exploring the potential of VNARs as future biotherapeutics. I remained in this role following the acquisition of Wyeth by Pfizer in 2009.

In 2012 I moved back into academia, setting up my own research group at the University of Aberdeen to study evolutionary immunology. I was promoted from Lecturer to Senior Lecturer in 2015. I re-joined the University of Maryland School of Medicine as an Assistant Professor in 2016 and was promoted to Associate Professor in 2023. Using cartilaginous fishes (i.e., chimera, sharks, skates, and rays) as our baseline my team are mapping the evolution of immune molecules and networks across vertebrate phylogeny to better understand the impact of change upon immune protection. We are also leading efforts to use VNARs as novel therapeutic and diagnostic agents.

Immunology, evolution, antibodies, sharks, biologics

Tan et al. The whale shark genome reveals patterns of vertebrate gene family evolution. Elife. 2021 Aug 19;10:e65394. PMID: 34409936.

Chen et al. Shark nanobodies with potent SARS-CoV-2 neutralizing activity and broad sarbecovirus reactivity. Nat Commun. 2023 Feb 3;14(1):580. PMID: 36737435.

Matz et al. Organized B cell sites in cartilaginous fishes reveal the evolutionary foundation of germinal centers. Cell Rep. 2023 Jul 25;42(7):112664. PMID: 37342909.

Ludwig et al. Multiparatopic antibodies induce targeted downregulation of programmed death-ligand 1. Cell Chem Biol. 2024 May 16;31(5):904-919.e11. PMID: 38679021.

Hill & Dooley. The unexpected role of nurse shark pancreas as a secondary lymphoid organ. J Immunol. 2025 Jul 1;214(7):1493-1503. PMID: 40373270.

A full list of my publications can be found at NCBI: My Bibliography - NCBI

Dooley H, Flajnik MF, Porter AJ. Selection and characterization of naturally occurring single-domain (IgNAR) antibody fragments from immunized sharks by phage display. Mol Immunol. 2003 Sep;40(1):25-33. PMID: 12909128.

Stanfield RL, Dooley H, Flajnik MF, Wilson IA. Crystal structure of a shark single-domain antibody V region in complex with lysozyme. Science. 2004 Sep 17;305(5691):1770-3. PMID: 15319492.

Dooley H, Flajnik MF. Shark immunity bites back: affinity maturation and memory response in the nurse shark, Ginglymostoma cirratum. Eur J Immunol. 2005 Mar;35(3):936-45. PMID: 15688348.

Dooley H, Flajnik MF. Antibody repertoire development in cartilaginous fish. Dev Comp Immunol. 2006;30(1-2):43-56. PMID: 16146649.

Dooley H, Stanfield RL, Brady RA, Flajnik MF. First molecular and biochemical analysis of in vivo affinity maturation in an ectothermic vertebrate. Proc Natl Acad Sci U S A. 2006 Feb 7;103(6):1846-51. PMID: 16446445.

Stanfield RL, Dooley H, Verdino P, Flajnik MF, Wilson IA. Maturation of shark single-domain (IgNAR) antibodies: evidence for induced-fit binding. J Mol Biol. 2007 Mar 23;367(2):358-72. PMID: 17258766.

Goodchild SA, Dooley H, Schoepp RJ, Flajnik M, Lonsdale SG. Isolation and characterisation of Ebolavirus-specific recombinant antibody fragments from murine and shark immune libraries. Mol Immunol. 2011 Sep;48(15-16):2027-37. PMID: 21752470.

Dooley H, Buckingham EB, Criscitiello MF, Flajnik MF. Emergence of the acute-phase protein hemopexin in jawed vertebrates. Mol Immunol. 2010 Nov-Dec;48(1-3):147-52. PMID: 20884052.

Li R, Dooley H, Wang T, Secombes CJ, Bird S. Characterisation and expression analysis of B-cell activating factor (BAFF) in spiny dogfish (Squalus acanthias): cartilaginous fish BAFF has a unique extra exon that may impact receptor binding. Dev Comp Immunol. 2012 Apr;36(4):707-17. PMID: 22155638.

Crouch K, Smith LE, Williams R, Cao W, Lee M, Jensen A, Dooley H. Humoral immune response of the small-spotted catshark, Scyliorhinus canicula. Fish Shellfish Immunol. 2013 May;34(5):1158-69. PMID: 23439398.

Pettinello R, Dooley H. The immunoglobulins of cold-blooded vertebrates. Biomolecules. 2014 Nov 24;4(4):1045-69. PMID: 25427250.

Li R, Redmond AK, Wang T, Bird S, Dooley H, Secombes CJ. Characterisation of the TNF superfamily members CD40L and BAFF in the small-spotted catshark (Scyliorhinus canicula). Fish Shellfish Immunol. 2015 Nov;47(1):381-9. PMID: 26386192.

Redmond AK, Pettinello R, Dooley H. Outgroup, alignment and modelling improvements indicate that two TNFSF13-like genes existed in the vertebrate ancestor. Immunogenetics. 2017 Mar;69(3):187-192. PMID: 28070614.

Pettinello R, Redmond AK, Secombes CJ, Macqueen DJ, Dooley H. Evolutionary history of the T cell receptor complex as revealed by small-spotted catshark (Scyliorhinus canicula). Dev Comp Immunol. 2017 Sep;74:125-135. PMID: 28433528.

Redmond AK, Ohta Y, Criscitiello MF, Macqueen DJ, Flajnik MF, Dooley H. Haptoglobin Is a Divergent MASP Family Member That Neofunctionalized To Recycle Hemoglobin via CD163 in Mammals. J Immunol. 2018 Oct 15;201(8):2483-2491. PMID: 30194112.

Redmond AK, Macqueen DJ, Dooley H. Phylotranscriptomics suggests the jawed vertebrate ancestor could generate diverse helper and regulatory T cell subsets. BMC Evol Biol. 2018 Nov 15;18(1):169. PMID: 30442091.

Matz H, Dooley H. Shark IgNAR-derived binding domains as potential diagnostic and therapeutic agents. Dev Comp Immunol. 2019 Jan;90:100-107. PMID: 30236879.

Redmond AK, Zou J, Secombes CJ, Macqueen DJ, Dooley H. Discovery of All Three Types in Cartilaginous Fishes Enables Phylogenetic Resolution of the Origins and Evolution of Interferons. Front Immunol. 2019 Jul 12;10:1558. PMID: 31354716.

Eve O, Matz H, Dooley H. Proof of long-term immunological memory in cartilaginous fishes. Dev Comp Immunol. 2020 Jul;108:103674. PMID: 32165114.

Bakke FK, Monte MM, Stead DA, Causey DR, Douglas A, Macqueen DJ, Dooley H. Plasma Proteome Responses in Salmonid Fish Following Immunization. Front Immunol. 2020 Oct 8;11:581070. PMID: 33133099.

Bakke FK, Gundappa MK, Matz H, Stead DA, Macqueen DJ, Dooley H. Exploration of the Nurse Shark (Ginglymostoma cirratum) Plasma Immunoproteome Using High-Resolution LC-MS/MS. Front Immunol. 2022 Jun 6;13:873390. PMID: 35734164.

Redmond AK, Pettinello R, Bakke FK, Dooley H. Sharks Provide Evidence for a Highly Complex TNFSF Repertoire in the Jawed Vertebrate Ancestor. J Immunol. 2022 Nov 1;209(9):1713-1723. PMID: 36113883.

Matz H, Dooley H. 450 million years in the making: mapping the evolutionary foundations of germinal centers. Front Immunol. 2023 Aug 11;14:1245704. PMID: 37638014.

I am an evolutionary immunologist interested in the development of new methods to understand, diagnose, and potentially treat human and animal diseases.

There are two main aspects to our work; the first is driven by a desire to understand when the different components of the immune system emerged and how they subsequently evolved. To do this we use a comparative approach, examining a specific immune molecule or pathway in many different animal species and comparing them to look for shared properties and/or rules that govern their function. An essential part of this are our studies on the immune response of sharks and their close relatives the skates, rays, and chimera (all cartilaginous fishes); this group are especially important as they are the most ancient species to have a ‘human-like’ adaptive immune system (with polymorphic/polygenic MHC molecules and diverse repertoires of immunoglobulins and T cell receptors generated by somatic recombination). We conducted long-term immunization studies in several species of shark and showed they can generate robust, antigen-specific antibody responses and that this response affinity matures over time. We have also demonstrated long term immunological memory in this lineage. More recently my team used a combination of single nucleus RNA sequencing (snRNA-seq) to characterize the cell types present in the spleen of immunized nurse sharks then RNAscope in situ hybridization to map the expression of lineage-defining genes to determine cellular organization. We identified ordered structures within the shark spleen with all the functional attributes required for efficient B cell selection. We hypothesize these structures are an evolutionary precursor of mammalian germinal centers (GCs).

The second aspect of our work is the development of shark-derived, target-specific nanobodies (called VNARs) to understand, diagnose, and potentially treat human and animal diseases. VNARs are the variable binding domains of the novel antibody isotype, IgNAR, which is only found in cartilaginous fishes. Despite their small size, VNARs bind antigens with sub-nanomolar affinities, target novel epitopes such as enzyme active sites, and are highly resistant to thermal denaturation, making them an interesting prospect for the development of new diagnostic reagents and future therapeutics. We have worked with external partners to develop VNAR-based immunodiagnostics and/or therapeutics for viral diseases of pandemic potential including Ebola and COVID-19. Additionally, we have active collaborations with several other research teams to raise VNARs against 'hard-to-hit' targets associated with human diseases such as cancer.

Awards

Teaching commendation, University of Maryland School of Medicine, for excellence in teaching on the MS1 Blood and Host Defenses course. 2023 

Distinguished lecturer award, University of Maryland School of Medicine, for exceptional dedication and excellence in teaching on the MS1 Blood and Host Defenses course. 2025.

Affiliations

Member of the International Society of Developmental & Comparative Immunology. 2000-present.

Member of the American Association of Immunologists. 2010-present.

Member of the American Association for the Advancement of Science. 2025-present.

Active grants

NIH RO1AI92916. Shark nanobodies identify pan-coronavirus spike sites of vulnerability for therapeutic intervention. (MPIs Dooley & Joyce). 05/2026-04/2031.

Recently completed grants

NIH R21AI175680. Shark nanobodies enable identification of pan-sarbecovirus and pan-merbecovirus spike RBD sites of vulnerability. (MPIs Dooley & Joyce). 02/2023-01/2025.

NIH R61AI54632. Self-test HIV diagnostics utilizing structurally novel, shark-derived binding domains. (MPIs Dooley & McDevitt). 01/2022-12/2024.

2025

AAI News 'Surprising Discovery Changes our Understanding of Shark Immune Systems'.

NPR 'The shark inside you’. 

Science News. 'Sharks may use an unexpected organ to fight microbial invaders'.

2022

Sydney Morning Herald. 'Breaking the wave: What will it take for us to get ahead of COVID-19?'

2019

Forbes. 'How Unlocking Shark Blood Secrets Helps Humans.'

2018

Science News. 'Small but mighty'.