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Dooley, Helen

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  • Dooley, Helen

Helen M. Dooley, PhD

  • Academic Title: Associate Professor
  • Primary Appointment: Microbiology and Immunology
  • Email: hdooley@som.umaryland.edu
  • Location: 701 E. Pratt St, Baltimore, MD 21202
  • Phone (Primary): +1-410-234-8837
  • Additional Publications
  • Research Interests
  • Awards and Affiliations
  • Grants and Contracts
  • In the News

Education and Training

 

B.Sc. Genetics (hons, first class), University of Aberdeen, UK. 1996.

M.Sc. Antibody Engineering (with distinction), University of Aberdeen, UK. 1998.

Ph.D. ‘Characterisation of single domain antibody fragments from the Nurse Shark, Ginglymostoma cirratum, using phage display’, University of Aberdeen, UK. 2001.

Associate Fellow of the Higher Education Academy (HEA), UK. 2013.

Biosketch

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 shark derived nanobodies (VNARs) as novel therapeutic and diagnostic agents.

Research/Clinical Keywords

Immunology, evolution, antibodies, sharks

Highlighted Publications

Tan M, Redmond AK, Dooley H, Nozu R, Sato K, Kuraku S, Koren S, Phillippy AM, Dove AD, Read T. The whale shark genome reveals patterns of vertebrate gene family evolution. Elife. 2021 Aug 19;10:e65394. PMID: 34409936.

Chen WH, Hajduczki A, Martinez EJ, Bai H, Matz H, Hill TM, Lewitus E, Chang WC, Dawit L, Peterson CE, Rees PA, Ajayi AB, Golub ES, Swafford I, Dussupt V, David S, Mayer SV, Soman S, Kuklis C, Corbitt C, King J, Choe M, Sankhala RS, Thomas PV, Zemil M, Wieczorek L, Hart T, Duso D, Kummer L, Yan L, Sterling SL, Laing ED, Broder CC, Williams JK, Davidson E, Doranz BJ, Krebs SJ, Polonis VR, Paquin-Proulx D, Rolland M, Reiley WW, Gromowski GD, Modjarrad K, Dooley H, Joyce MG. Shark nanobodies with potent SARS-CoV-2 neutralizing activity and broad sarbecovirus reactivity. Nat Commun. 2023 Feb 3;14(1):580. PMID: 36737435.

Matz H, Taylor RS, Redmond AK, Hill TM, Ruiz Daniels R, Beltran M, Henderson NC, Macqueen DJ, Dooley H. 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 SD, Meksiriporn B, Tan J, Kureshi R, Mishra A, Kaeo KJ, Zhu A, Stavrakis G, Lee SJ, Schodt DJ, Wester MJ, Kumar D, Lidke KA, Cox AL, Dooley H, Nimmagadda S, Spangler JB. Multiparatopic antibodies induce targeted downregulation of programmed death-ligand 1. Cell Chem Biol. 2024 May 16;31(5):904-919.e11. PMID: 38679021.

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

Additional Publications

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.

Rumfelt LL, Lohr RL, Dooley H, Flajnik MF. Diversity and repertoire of IgW and IgM VH families in the newborn nurse shark. BMC Immunol. 2004 May 6;5:8. PMID: 15132758.

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.

Flajnik MF, Dooley H. The generation and selection of single-domain, v region libraries from nurse sharks. Methods Mol Biol. 2009;562:71-82. PMID: 19554288.

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.

Smith LE, Crouch K, Cao W, Müller MR, Wu L, Steven J, Lee M, Liang M, Flajnik MF, Shih HH, Barelle CJ, Paulsen J, Gill DS, Dooley H. Characterization of the immunoglobulin repertoire of the spiny dogfish (Squalus acanthias). Dev Comp Immunol. 2012 Apr;36(4):665-79. PMID: 22040740.

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.

Müller MR, O'Dwyer R, Kovaleva M, Rudkin F, Dooley H, Barelle CJ. Generation and isolation of target-specific single-domain antibodies from shark immune repertoires. Methods Mol Biol. 2012;907:177-94. PMID: 22907351.

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.

Li R, Wang T, Bird S, Zou J, Dooley H, Secombes CJ. B cell receptor accessory molecule CD79α: characterisation and expression analysis in a cartilaginous fish, the spiny dogfish (Squalus acanthias). Fish Shellfish Immunol. 2013 Jun;34(6):1404-15. PMID: 23454429.

Castro CD, Ohta Y, Dooley H, Flajnik MF. Noncoordinate expression of J-chain and Blimp-1 define nurse shark plasma cell populations during ontogeny. Eur J Immunol. 2013 Nov;43(11):3061-75. PMID: 23897025.

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

Zou J, Redmond AK, Qi Z, Dooley H, Secombes CJ. The CXC chemokine receptors of fish: Insights into CXCR evolution in the vertebrates. Gen Comp Endocrinol. 2015 May 1;215:117-31. PMID: 25623148.

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.

Munir D, Munro ES, Secombes CJ, Dooley H. Atlantic salmon kidney (ASK) cells are an effective model to characterise interferon (IFN) and IFN-induced gene expression following salmonid alphavirus infection. Fish Shellfish Immunol. 2020 Nov;106:792-795. PMID: 32871248.

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.

Matz H, Munir D, Logue J, Dooley H. The immunoglobulins of cartilaginous fishes. Dev Comp Immunol. 2021 Feb;115:103873. PMID: 32979434.

Tan M, Redmond AK, Dooley H, Nozu R, Sato K, Kuraku S, Koren S, Phillippy AM, Dove AD, Read T. The whale shark genome reveals patterns of vertebrate gene family evolution. Elife. 2021 Aug 19;10:e65394. PMID: 34409936.

Dooley H. Generation of VNAR Libraries from Immunized Sharks and Selection of Target-Specific Clones. Methods Mol Biol. 2022;2421:57-72. PMID: 34870811.

Buckley KM, Dooley H. Immunological Diversity Is a Cornerstone of Organismal Defense and Allorecognition across Metazoa. J Immunol. 2022 Jan 15;208(2):203-211. PMID: 35017209.

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.

Chen WH, Hajduczki A, Martinez EJ, Bai H, Matz H, Hill TM, Lewitus E, Chang WC, Dawit L, Peterson CE, Rees PA, Ajayi AB, Golub ES, Swafford I, Dussupt V, David S, Mayer SV, Soman S, Kuklis C, Corbitt C, King J, Choe M, Sankhala RS, Thomas PV, Zemil M, Wieczorek L, Hart T, Duso D, Kummer L, Yan L, Sterling SL, Laing ED, Broder CC, Williams JK, Davidson E, Doranz BJ, Krebs SJ, Polonis VR, Paquin-Proulx D, Rolland M, Reiley WW, Gromowski GD, Modjarrad K, Dooley H, Joyce MG. Shark nanobodies with potent SARS-CoV-2 neutralizing activity and broad sarbecovirus reactivity. Nat Commun. 2023 Feb 3;14(1):580. PMID: 36737435.

Jia Z, Feng J, Dooley H, Zou J, Wang J. The first crystal structure of CD8αα from a cartilaginous fish. Front Immunol. 2023 Apr 14;14:1156219. PMID: 37122697.

Srinivasan Rajsri K, McRae MP, Christodoulides NJ, Dapkins I, Simmons GW, Matz H, Dooley H, Fenyö D, McDevitt JT. Simultaneous Quantitative SARS-CoV-2 Antigen and Host Antibody Detection and Pre-Screening Strategy at the Point of Care. Bioengineering (Basel). 2023 Jun 1;10(6):670. PMID: 37370601.

Matz H, Taylor RS, Redmond AK, Hill TM, Ruiz Daniels R, Beltran M, Henderson NC, Macqueen DJ, Dooley H. Organized B cell sites in cartilaginous fishes reveal the evolutionary foundation of germinal centers. Cell Rep. 2023 Jul 25;42(7):112664. PMID: 37342909.

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.

Ludwig SD, Zhu A, Maremanda AP, Dooley HM, Spangler JB. Design and Construction of Antibody Fusion Proteins Incorporating Variable New Antigen Receptor (VNAR) Domains. Methods Mol Biol. 2024;2720:17-33. PMID: 37775655.

Ludwig SD, Meksiriporn B, Tan J, Kureshi R, Mishra A, Kaeo KJ, Zhu A, Stavrakis G, Lee SJ, Schodt DJ, Wester MJ, Kumar D, Lidke KA, Cox AL, Dooley HM, Nimmagadda S, Spangler JB. Multiparatopic antibodies induce targeted downregulation of programmed death-ligand 1. Cell Chem Biol. 2024 May 16;31(5):904-919.e11. PMID: 38679021.

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

Hajduczki A, Chang WC, De La Barrera R, Wood JF, Chen WH, Martinez EJ, Jensen JL, Sankhala RS, Smith C, Anderson A, Morrison EB, Peterson CE, Rees PA, Soman S, Kuklis C, Ahmed A, King J, Nasar F, Corbitt C, Choe M, Thomas PV, Zemil M, Wieczorek L, Polonis VR, Dooley HM, Mascola JR, de Val N, Matyas GR, Rao M, Gromowski GD, Modjarrad K, Vasan S, Froude JW, Michael NL, Joyce MG, Zarling S. Production of Clinical-Grade SARS-CoV-2 Spike Ferritin Nanoparticle Protein Immunogen by Transient Transfection. Vaccines (Basel). 2025 Oct 9;13(10):1041. PMID: 41150429.

 

Research Interests

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.

Awards and Affiliations

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.

 

Grants and Contracts

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.

In the News

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'.

 

Video

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.

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