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Alan Parker

Professor Alan Parker

Professor of Translational Virotherapies. Head of Section of Solid Cancers, Division of Cancer and Genetics

School of Medicine

Email
ParkerAL@cardiff.ac.uk
Telephone
+44 29225 10231
Campuses
Henry Wellcome Building for Biomedical Research, Room 3F08, University Hospital of Wales, Heath Park, Cardiff, CF14 4XN
Comment
Media commentator
Users
Available for postgraduate supervision

Overview

I have a long standing interest in virology and how this can be applied to cancer therapies using "oncolytic" adenoviral based vectors ("virotherapy"), that stems back to my PhD (awarded in 2003 from the University of Birmingham.)

Prior to relocating to Cardiff, I was studying adenoviral vectors for translational applications in cardiovascular disease, where my research had pinpointed key virus interactions with host blood coagulation factors (most notably Factor X) that dictate the tropism and toxicity of intravenously administered viral vectors. I relocated to Cardiff University in 2013, driven by a long term ambition to lead a world leading team developing “virotherapies” for treatment of cancer. Immediately following my recruitment, I began to develop a team, which now numbers almost 20. I was promoted to Senior Lecturer in 2014, to Reader in 2018, and to Personal Chair in 2020.

Research within my group focusses on several aspects of adenovirology, with the overarching aim of developing more selective and efficacious virotherapies for translational applications in cancer, namely:

  1. Defining and genetically precluding dose limiting interactions between virus and host cells, proteins and receptors.
  2. Developing targeting technologies that efficiently enable adenoviral vectors to infect cancerous cells, leaving "normal" cells non-infected.
  3. Developing new serotypes of Adenoviral vectors with new and exciting tropisms for translational applications.

I am a registered STEMNet ambassador (http://networking.stemnet.org.uk/user/30519), and passionate about the need to engage with the lay community to convey science. I play a leading role in a range of engagement activities, including presenting at the annual BSGCT public engagement day preceding the annual conference, and also at events “in house” at Cardiff University, where I have featured in several blog articles (e.g. see https://www.bsgct.org/virotherapy-showcased-at-cardiff-cancer-open-day/ and https://www.youtube.com/watch?v=3iZquZ4K5E4). In my role as a STEM ambassador, I regularly attend my local school to engage the students in gene therapy and my role as a scientist, and helped out with mock interviews. My involvement and engagement activities have featured in a School of Medicine Case Study (see https://www.cardiff.ac.uk/medicine/about-us/engagement/case-study-dr-alan-parker).  I have also written lay articles for both the BSGCT blog (https://www.bsgct.org/author/alanparker/) and ASGCT educational resources. I am passionate about improving career prospects for early career researchers (ECRs), and as a board member of the British Society for Gene and Cell Therapy, I have established and run a subcommittee devoted to development of Early Career Researchers, as well as updating the BSGCT facebook page (www.facebook.com/BSGCT) and twitter feed (@_BSGCT) as part of my role on the BSGCT communication & promotion subcommittee.

Publication

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Articles

Book sections

Websites

Research

Adenovirus Virology

Research within the Parker laboratory is focussed on developing bespoke oncolytic adenoviral vectors for translational cancer applications. To achieve this, we are developing tumour selective virotherapies that selectively infect cancer cells, leaving normal cells uninfected.  To achieve this, we take two approaches.  Our first approach is a “bottom up” approach involving the use of Ad5, a well described, well understood and clinically well studied virus. Although safe, Ad5 has a number of features which limits efficacy as a tumour selective virotherapy.

Firstly, the primary Ad5 receptor, hCAR (human coxsackie and adenovirus receptor) is ubiquitously expressed on red blood cells and in all tissues, located at tight junctions, but is commonly downregulated or even absent in advanced cancers, and therefore represents a poor target for tumour targeting strategies.

Secondly, uptake into immune cells, mediated by the interaction between αvβ3/5 integrin and the Ad5 penton base protein can promote significant dose limiting toxicities.

Finally, intravascular delivery of Ad5, a pre-requisite for therapy of metastatic disease, is compromised for Ad5 due to the high affinity interaction with the blood clotting factor, FX, which bridges the virus: FX complex to HSPGs and is responsible for the significant levels of hepatic uptake of Ad5 based virotherapies (overviewed in figure 1). To target the refined, basal vector to tumour cells, we further modulate the vector to incorporate peptide ligands binding to tumour specific markers, such as αvβ6 integrin (figure 2).

Our second approach represents a “top down” approach. Ad5 represents just one of a diverse family of viruses, presently numbering 57 serotypes, spanning 7 species (A-G). Many of these viruses have unique tropisms, mediated through interactions with as yet undocumented receptors.  Furthermore, many of these alternative Ad serotypes are rarely isolated and therefore have very limited levels of pre-existing immunity in the general population, which is likely to be advantageous when using them clinically.

We are exploring the natural diversity of Ad tropism by seeking to develop vectors based on rarely isolated Ads from species B and D.  We investigate potential receptor interactions at the molecular level by resolving the structure of the major tropism determining epitopes in super-high resolution by X-ray diffraction, and biologically by using sophisticated molecular techniques to generate chimeric viral vectors. Our recent Nature Communcations paper on species D structure and function (which can be access here http://dx.doi.org/10.1038/s41467-019-08599-y) was recently featured in several news outlets and was covered in a press release (http://www.cardiff.ac.uk/news/view/1442255-seeing-the-unseeable)

Our research on targeted virotherapies was recently featured online on the BBC news website:

http://www.bbc.co.uk/news/uk-wales-south-east-wales-40305580

https://www.bbc.co.uk/news/uk-wales-44237820

As well as featuring on BBC Wales today:

https://youtu.be/JIH9qvpnb_g

In the below link, we describe our recently funded CRUK project, developing adenoviral based virotherapies that are “trained” to fight ovarian cancer:

https://www.youtube.com/watch?v=DDQPpZHZbo0&t=12s

Our research was also highlighted in a recent (Autumn 2017) edition of Advances Wales (p12)

https://businesswales.gov.wales/sites/business-wales/files/documents/171027_Advances83_EnglishSection_2.pdf

Our collaborative research with Gunnel Hallden (Bart's Cancer Institute) on targeted virotherapies for pancreatic cancer was subject of some significant press coverage - and we look forward to extending this exciting translational collaboration further!

http://www.cardiff.ac.uk/news/view/1083809-inhibiting-the-growth-of-pancreatic-cancer

http://www.independent.co.uk/news/health/flu-virus-cancer-treatment-pancreas-research-discovery-a8176116.html

Teaching

I perform a wide range of teaching engagements for the University, as well as a significant teaching and engagement for the wider community.  Specifically, within Cardiff university I:

  • Design and perform Student Selected Components (SSCs) for undergraduate medical students.
  • Run tutorials for medical students on how to critically review scientific papers.
  • Perform virology tutorials and lectures as part of the undergraduate programme.
  • Act as a personal tutor to undergraduate medical students.
  • Act as PhD panel appraiser for >10 PhD students within the Divisions of Cancer and Genetics and Division of Infection and Immunity.
  • Supervise undergraduate research projects.
  • Supervise ERASMUS student projects.
  • Supervise PTY student projects.
  • Act as an assessor for undergraduate research projects.
  • Act as a personal mentor for 7 PhD students across the Divisions of Cancer and Genetics and Infection and Immunity.
  • Regularly acting as a PhD panel member for PhD student vivas (presently 6 times as an external examiner, 3 times as an internal examiner and 13 times as viva chair).

Biography

My interest in gene and cell therapy began whilst studying for my undergraduate degree in Genetics (University of Sheffield), which inspired me to pursue a PhD in this field.  My PhD was performed under the supervision of Prof Len Seymour (now at the University of Oxford) at the CRUK Institute for Cancer Studies at the University of Birmingham, and I completed my thesis entitled "Development of Peptide Targeted Gene Delivery Systems" in 2003.

My first postdoctoral position was under the supervision of Prof John Fabre, where I developed novel bioresponse peptide systems for local gene delivery (2003-2005) and I published several articles from this post. Whilst in this position I also developed and patented a versatile, highly organised form of nanoparticle for rapid, targetable delivery of drugs or mRNA/miRNAs into the cytoplasm of target cells (Collins L, Parker AL et al, ACS Nano, 2010).

My desire to work on viral vectors for gene and cell therapy applications resulting in my relocating to Glasgow University from 2005-2013, where I made important contributions to how Adenoviral (Ad) based vectors interact with host cells and proteins, and how these interactions dictate viral tropism and toxicity.  In 2007 I was awarded a prestigious RSE Personal Fellowship to generate safer and more efficacious Ad based vectors for in vivo applications.  In 2010-2013 I was a BHF funded Senior Scientist.  During this period I published a number of high impact articles (Cell, Blood, PLoS pathogens, Molecular Therapy, Journal of Virology), and patented the use of a novel Ad serotype for gene therapy applications.

In 2013 my desire to apply my adenoviral knowledge in the cancer setting resulted in my relocation to Cardiff University as a Lecturer and group leader.  In 2014 I was promoted to Senior Lecturer,  the to Reader in 2018, and to Professor of Translational Virotherapies in 2020. Since 2020 I lead the targeted therapeutic programme of the HCRW funded Wales Cancer Research Centre (https://www.walescancerresearchcentre.org/wcrc/). I have been an elected board member of the British Society for Gene and Cell Therapy (https://www.bsgct.org/) since 2014, and have been Treasurer for the society since 2020.

I am fortunate to lead a expanding and hugely talented group of dedicated individuals within the Division of Cancer and Genetics, where we are progressing next generation "precision immunovirotherpies" towards the clinic, underpinned by fanstatic support from our major funders, Cancer Research UK, Cance Research Wales, Tenovus Cancer Care, Health and Care Research Wales and KESS 2.

Honours and awards

  • Programme lead for the Wales Cancer Research Centre: Targeted Therapeutics (2020-2025)
  • Treasurer of the British Society for Gene and Cell Therapy (2020-2024)
  • Organiser and chair of the local organising committee for the 14th Annual Meeting of the British Society for Gene and Cell Therapy (Cardiff, April 2017)
  • Participant in Welsh Crucible 2015.
  • Elected BSGCT Board member (2014-2017, re-elected in 2017-2020), where I established and chair the Early Career Development and Collaboration subcommittee and play an active role as a member of the communication and promotion subcommittee.
  • Awarded 2006 “Excellence in Research Award” by the American Society for Gene and Cell therapy for my research on adenoviral vectors and their interactions with coagulation factors.
  • Runner up, NEXXUS “Young Biomedical Researcher of the Year” category 2007.
  • Awarded highly competitive Royal Society of Edinburgh Fellowship in the Biomedical Sciences (2007-2010) to develop adenoviral vectors devoid of coagulation factor interactions for in vivo applications.
  • Travel Grant Awardee, American Society of Gene and Cell Therapy, 2006 & 2008.
  • Grant committee member - NC3Rs.
  • Grant reviewer for MRC, Worldwide Cancer Research, the French National Research Agency, Fonds de recherche du Québec – Santé and Wellbeing of Women.
  • Regular manuscript reviewer for a range of high impact journals.
  • BSGCT session chair 2012, 2014, 2016, 2017.
  • Editorial board – Chemotherapy journal.
  • Abstract reviewer for BSGCT, ASGCT and ESGCT.

Professional memberships

  • Founding member of the British Society for Gene and Cell Therapy (2003-), elected board member (2014-17), chair of the Early Career Development and Collaboration subcommittee, vice chair of the Membership and Awareness subcommittee, and memeber of the Public Engagement subcommittee.
  • Associate Member of the American Society of Gene and Cell Therapy (2003-), and I have written lay patient orientation perspectives for the ASGCT website on recent developments in the gene therapy field.
  • Member of the Microbiology Society (formerly the Society for General Microbiology)
  • I am a registered STEMNET ambassador, and as such I devote my own time to outreach activities in local schools seeking to inspire new generations of children into science.  I also perform a significant engagement activities with local patient support groups and charities.  My engagement activities are significant enough to have formed the basis for a case report by Cardiff University School of Medicine.

Academic positions

August 2020 - Present: Professor of Translational Virotherapies, Cardiff University School of Medicine.

August 2018 - July 2020: Reader in Translational Virotherapies, Cardiff University School of Medicine.

August 2014 - July 2018: Senior Lecturer in Translational Oncology, Cardiff University School of Medicine.

February 2013 - July 2014: Lecturer in Translational Oncology, Cardiff University School of Medicine.

October 2010 – January 2013: BHF Senior Scientist, BHF Glasgow Cardiovascular Research Centre (GCRC), University of Glasgow.

October 2007 – September 2010: Royal Society of Edinburgh Fellow in the Biomedical Sciences, BHF Glasgow Cardiovascular Research Centre (GCRC), University of Glasgow.

September 2005 – September 2007: Research Associate BHF Glasgow Cardiovascular Research Centre (GCRC), University of Glasgow.

August 2003 – August 2005: Research Associate, King’s College London (Department of Clinical Sciences).

Committees and reviewing

Internal committees:

  • 2017 - present: member of the DCG EDI committee
  • 2015 – present: Seminar series organiser for the Institute of Cancer & Genetics, Cardiff University, UK.
  • 2014 – present: GMBA committee member, College of Biomedical & Life Sciences, Cardiff University, UK.
  • 2013 – present: Student Review Panel, Division of Cancer & Genetics and Division of Infection & Immunity, Cardiff University, UK.
  • 2007 – 2013: Member of GM committee, Institute of Cardiovascular & Medical Sciences, Glasgow University, UK
  • 2007 – 2013    Biological Safety Officer, Institute of Cardiovascular & Medical Sciences, Glasgow University, UK

External Committees

  • National oversight group - cell and gene therapies in Wales
  • 2015 - present: NC3Rs CrackIT review panel member
  • Abstract committee reviewer for American Society for Gene and Cell Therapy
  • Abstract committee reviewer for British Society for Gene and Cell Therapy
  • Abstract committee reviewer for European Society for Gene and Cell Therapy
  • Grant reviewer for MRC, Worldwide Cancer Research, the French National Research Agency, Fonds de recherche du Québec – Santé and Wellbeing of Women

Supervisions

My team is a thriving mix of fellows, postdoctoral staff, research students and technical staff. They are a pleasure to work with.

We are delighted to be working with Dr Carly Bliss since June 2020, who joins us as an independent research fellow (funded by Wellcome ISSF Research Fellowship funding), developing our viral platforms as vaccines for cancer and for infectious diseases.

The following postdoctoral researchers are presently employed in my group

  • Dr Rebecca Bayliss (funded by Cancer Research UK).
  • Dr Luned Badder (funded by Cancer Research Wales).
  • Dr Mahulena Marsukova (funded by ECMC/WCRC)
  • Dr Charley Lovatt (funded by NIHR)
  • Dr Emily Bates (funded by ECMC)

The group is supported by two fantastic technical members of staff

  • Mrs Joanne Jones.
  • Dr Andy Robnson.

Within the group, I currently supervise to the following PhD/MD/Phil students

  • Tabitha Cunliffe (funded by KESS2/Tenovus; co-supervised Prof Arwyn Jones (Pharmy) and Prof Alfonso Jaramillo (Warwick).
  • Emily Bates (funded by Cardiff University School of Medicine; co-supervised by Prof John Chester).
  • Alicia Teijeira-Crespo (funded by Cancer Research Wales; co-supervised my Prof Awen Gallimore & Prof Andy Godkin)
  • Elise Moses (funded by ISSF Translational Kickstarter award/Velindre Charitable funds; co-supervised by Dr James Davies, Dr Richard Stanton, Dr Mererid Evans and Dr David Cole).
  • Rebecca Wallace (funded by Cancer Research UK, co-supervised by Prof Awen Gallimore and Dr Carly Bliss).
  • Emma Swift (funded by Cancer Research UK, co-supervised by Dr Pierre Rizkallah and Dr James Davies).
  • Rosie Mundy (funded by GW4, co-supervised by Dr David Matthews (Bristol), Dr Carly Bliss and Dr Pierre Rizkallah).
  • Adam Naskretski (part funded by South East Wales Gyncological fund, co-supervised by Toby Phesse, Sadie Jones and Rebecca Bayliss).
  • Bethan Carter (WCAT).

I presently supervise the following undergraduate research projects

  • James Thetford (PTY Student, Cardiff University): 5T4 as an adenoviral entry receptor
  • Caitlin Dop (PTY student, Cardiff University): Design of universal coronavirus vaccines

I am interested in supervising PhD/MD students in following areas:

  • Cancer virotherapies
  • Drug delivery
  • Vaccine development
  • Gene Therapy
  • Virology (with particular emphasis on adenoviral vectors)
  • Virus: host interactions
  • Immunotherapies

Combination therapies involving virotherapies (including radiotherapies, chemotherapies, immunotherapies, epigenetic therapies)

Current supervision

Emily Bates

Emily Bates

Research student

Rosie Mundy

Rosie Mundy

Research student

Rebecca Wallace

Rebecca Wallace

Research student

Emma Swift

Emma Swift

Research student

Adam Naskretski

Adam Naskretski

Research student

Alicia Teijeira Crespo

Alicia Teijeira Crespo

Research student

Engagement

I perform a significant amount of engagement activity on behalf of both School and for the British Society for Gene and Cell Therapy.  I am a registered STEMNet ambassador, and regularly attend a variety of events including school outreach events to public and patient engagement events and science festivals, as well as writing lay blog articles on gene and cell therapy (see https://www.bsgct.org/author/alanparker/).  My commitment to engagement has resulted in my featuring in a School of Medicine "Public Engagement and Involvement in Research" case study which can be accessed here https://www.cardiff.ac.uk/medicine/about-us/engagement/case-study-dr-alan-parker, and was also featured in the 2018 School of Medicine - Public Engagement and Involvement Annual Report, which can be accessed here https://www.cardiff.ac.uk/__data/assets/pdf_file/0010/1367875/Cardiff-University-School-of-Medicine-Public-Engagement-and-Involvement-Annual-Report-2017-18-.pdf