Helen M. Dooley, PhD

Redmond, A.K., Pettinello, R. & Dooley, H. (2017). Outgroup, alignment, and modellingimprovements indicate that two TNFSF13-like genes existed in the vertebrate ancestor. Immunogenetics (in press).

Li, R., Redmond, A.K., Wang, T., Bird, S., Dooley, H. & Secombes, C.J. (2015). Characterisation of the TNF superfamily members CD40L and BAFF in the small-spotted catshark (Scyliorhinus canicula). Fish & Shellfish Immunology. 47; 381-389

Zou, J., Redmond, A.K., Qi, Z., Dooley, H. Secombes, C.J. (2015). The CXC chemokine receptors of fish: insights into CXCR evolution in the vertebrates. General & Comparative Endocrinology215; 117-131

Pettinello, R. & Dooley, H. (2014). The immunoglobulins of cold-blooded vertebrates. Biomolecules 4; 1045-1069

Castro, C.D., Ohta, Y., Dooley, H. & Flajnik, M.F. (2013). Non-coordinate expression of J-chain and Blimp-1 define nurse shark plasma cell populations during ontogeny. European Journal of Immunology43; 3061-3075

Li, R., Wang, T., Bird, S., Zou, J., Dooley, H. & Secombes, C. (2013). B cell receptor accessory molecule CD79a; characterisation and expression analysis in a cartilaginous fish, the spiny dogfish (Squalus acanthias).Fish & Shellfish Immunology. 34; 1395-1752.

Crouch, K., Smith, L.E., Williams, R., Jensen, A. & Dooley, H. (2013). Humoral immune response of the small-spotted catshark, Scyliorhinus canicula. Fish & Shellfish Immunology. 34; 1158-1169

Li, R., Dooley, H., Wang, T., Secombes, C. & Bird, S. (2012). Characterisation and expression analysis of B-cell activating factor (BAFF) in the spiny dogfish (Squalus acanthias): Cartilaginous fish BAFF has a unique extra exon that may impact receptor binding. Developmental & Comparative Immunology. 36; 707-717

Smith, L.E., Crouch, K., Cao, W., Müller, M.R., Wu, L., Steven, J., Lee, M., Liang, M., Flajnik, M.F., Shih, H., Barelle, C.J., Paulsen, J., Gill, D.S. & Dooley, H. (2012). Characterization of the immunoglobulin repertoire of spiny dogfish (Squalus acanthias). Developmental & Comparative Immunology. 36; 665-679

Tchistiakova, L., Finlay, W.J.J., Olland, S., Dooley, H. & Gill, D. (2011). Antibody fragments and alternate protein scaffolds. Antibody Drug Discovery (Imperial College Press).

Goodchild, S., Dooley, H., Schoepp, R.J., Flajnik, M.F. & Lonsdale, S.G. (2011). Isolation and characterisation of Ebolavirus-specific recombinant antibody fragments from murine and shark immune libraries. Molecular Immunology. 48; 2027-37

Dooley, H., Buckingham, E.B., Criscitiello, M.F. & Flajnik, M.F. (2010). Emergence of the acute-phase protein hemopexin in jawed vertebrates. Molecular Immunology. 48; 147-152

Flajnik, M.F. & Dooley, H. (2009). The generation and selection of single-domain V region libraries from nurse sharks. Methods in Molecular Biology. 562; 71-82

Stanfield, R.L., Dooley, H.,Verdino, P., Flajnik, M.F. & Wilson, I.A. (2007). Maturation of shark single-domain (IgNAR) antibodies: Evidence for induced fit binding. Journal of Molecular Biology. 367; 358-372

Dooley, H., Stanfield, R.L., Brady, R.A. & Flajnik, M.F. (2006). First molecular and biochemical analysis of in vivo affinity maturation in an ectothermic vertebrate. PNAS USA. 103; 1846-185

Dooley, H. & Flajnik, M.F. (2006) Antibody repertoire development in cartilaginous fish.  Developmental & Comparative Immunology.  30; 43-56

Dooley, H. & Flajnik, M.F. (2005). Shark immunity bites back: affinity maturation and memory response in the nurse shark, Ginglymostoma cirratum. European Journal of Immunology.35; 936-945

Stanfield, R.L., Dooley, H.,Flajnik, M.F. & Wilson, I.A. (2004).Crystal structure of a sharksingle domain antibody V region in complex with lysozyme. Science305; 1770-1773

Rumfelt, L.L., Lohr, R.L., Dooley, H. & Flajnik, M.F.  (2004). Diversity and repertoire of IgW and IgM VH families in the newborn nurse shark.  BMC Immunology 5; 8

Dooley, H., Flajnik, M.F.& Porter, A.J. (2003). Selection and characterization of naturally occurring single-domain (IgNAR) antibody fragments from immunized sharks by phage display.  Molecular Immunology  40; 25-33

Dooley, H., Grant, S.D., Porter, A.J. & Harris, W.J. (1998). Stabilisation of antibody fragments in adverse environments. Biotechnology & Applied Biochemistry 28; 77-83

Shelton, S.A., Graham, B.M., Strachan, G., Dooley, H.,Porter, A.J. & Harris, W.J. (1998). Immunomethods for detecting a broad range of polychlorinated biphenyl’s. Food & Agricultural Immunology 10; 37-45

Book chapters

Dooley, H. (2014). Athena and the evolution of adaptive immunity. Chapter 2 (p24-50) in Immunobiology of the Shark, Taylor and Francis Group, LLC. Eds Smith, S., Sim, B., Flajnik, M.F.

Muller, R.M., ODwyer, R., Kovaleva, M., Rudkin, F., Dooley, H. & Barelle, C.J. (2012). Generation and isolation of target-specific single-domain antibodies from shark immune repertiores. Methods in Molecular Biology: Antibody engineering. Methods and Protocols, Humana Press; vol 907. p177-194

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

There are two main aspects to my work; the first is driven by a desire to understand how the components of the immune system emerged and have since evolved. To do this I 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 have previously conducted long-term immunization studies in a number of species of shark and shown they can generate robust, antigen-specific antibody responses, despite lacking isotype switching and conventional germinal centres. We have now moved on to study the molecules involved in B cell development/maintenance and regulation of the adaptive response. As cartilaginous fish are still relatively understudied from a genomic perspective we use next-generation sequencing to generate high-coverage, multi-tissue transcriptomes, that can be searched for immune molecules of interest. Our recent findings suggest the molecules required for B cell maintenance may differ between fishes and other vertebrates and we are now investigating these molecules using techniques such as quantitative PCR, recombinant protein production, structural analysis, proteomics, as well as conductingfunctional studies in vitro/vivo.

The second aspect of my work is the development of new technologies/therapies to understand, diagnose, and potentially treat, human and animal disease. During our research we often come across novel molecules that sharks (and other species) use to detect infection and protect themselves from disease; with sufficient development, some of these molecules may provide the next-generation of diagnostic and therapeutic agents. A large part of my work to date has focussed upon the novel antibody isotype, IgNAR, which is only found in the cartilaginous fishes. IgNAR is a heavy chain homodimer that does not associate with light chains; instead it is capable of binding antigen with high affinity via a single variable domain (VNAR). Due to their small size, high stability and ability to target novel epitopes, such as active sites or deep clefts on the surface of proteins, there is much interest in developing VNARs as new diagnostic reagents and therapeutics. We have previously developed VNARs that could be used to detect anthrax bacteria and Ebola virus, and have ongoing projects looking at the utility of VNARs as diagnostics, imaging agents and/or therapeutics for cancer and other human diseases such as HIV.

Active grants & contracts

Oct 2016: EASTBIO PhD studentship (Supervisor; £88K over 4 years). ‘Development of a proteomics platform to monitor immune responses in non-mammals.’

Sep 2012: PhD studentship with the Centre for Genome Enabled Biology & Medicine (CGEBM), University of Aberdeen, UK (Supervisor; £50K over 3.5 years). ‘Exploiting shark sequence data to understand vertebrate evolution’.

Completed grants & contracts

Sep 2015: Scottish Crucible award (Co-Investigator; £3.5K over 12 months). ‘Play to Promote: Developing Innovative Games for the Communication & Promotion of Science’.

Apr 2015: BBSRC-NERC project grant (PI; £195K for 18 months). ‘Development of a proteomic platform to facilitate the generation of new and improved vaccines for use in aquaculture’.

Mar 2014: The Royal Society research grant (PI; £15K over 12 months); ‘Development of the small-spotted catshark (Scyliorhinus canicula) as a model to study the evolution of the adaptive immune system’.

Jan 2014: Encompass Kick Start Award (PI; £10K over 12 months); ‘Generation of antibodies against lesser-spotted catshark IgNAR to aid the future generation of novel diagnostic and therapeutic agents’.

Sep 2013: Worldwide Cancer Research project grant (PI; £202K over 3 years); ‘Generation of novel antibody-based HER2:HER3 heterodimerisation inhibitors’.

Feb 2013: Pump-Priming funding from the University of Aberdeen's Environment and Food Security Interdisciplinary Research Theme (PI; £1.5K) for ‘Preliminary studies on the expression of IgD in bony fishes’.

2009: BBSRC industrial (CASE) PhD studentship with University of Aberdeen (Industrial supervisor; £40K for 4 years).

2005: UK government contract work (Researcher co-investigator; $110K over 2 years).

2002: NIH R21 (Researcher; $500K over 18 months); ‘Highly stable, anthrax-specific shark antibody fragments’.

How Sharks Are Helping Scientists at the UMSOM

Every week is shark week for Dr. Helen Dooley. Dr. Dooley is an evolutionary immunologist, and assistant professor of Microbiology and Immunology at the University of Maryland School of Medicine. In her lab at the Institute of Marine and Environmental Technology (IMET), Dr. Dooley studies sharks to develop new methods to understand, diagnose, and potentially treat, human and animal diseases, including cancer.