Dr Alan Parker

Dr Alan Parker

Senior Lecturer

School of Medicine

Email:
parkeral@cardiff.ac.uk
Telephone:
+44 (0)29 22 510 231
Location:
Henry Wellcome Building for Biomedical Research, University Hospital of Wales, Heath Park, Cardiff, CF14 4XN
Media commentator

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, now numbering 5, and was promoted to Senior Lecturer in 2014.

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.

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 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 bio response peptide systems for local gene delivery (2003-2005) and I published several articles from this post. Whilst in this position I also developed a versatile, highly organised form of nanoparticle (now patent protected) 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 seminal 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, and my group is now becoming established within the Division of Cancer and Genetics.

Honours and awards

  • 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 EXEC member (2014-17) and co-chair of the BSGCT membership and awareness 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 2014 - Present: Senior Lecturer/Group Leader in Translational Oncology, Cardiff University School of Medicine.

February 2013-July 2014: Lecturer/Group Leader 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).

Speaking engagements

I have spoken at 6 major international gene therapy and virology conferences, including invitations to the American Society of Gene Therapy 2006, where I received the ASGCT “Excellence in Research Award”. I also received travel grants for high scoring abstract in 2007 and 2008.

I have also given 15 invited talks at various institutes across the UK and around the world.

Committees and reviewing

Internal committees:

  • 2017 - present: member of the DCG EDHR 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

  • 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

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).

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 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

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 

The following postdoctoral researchers are presently employed in my group

  • Dr James Davies (funded by Cancer Research UK)
  • Dr Sarah Curtis (funded by Life Sciences Research Network Wales)

I am currently lead supervisor to the following PhD/MD students

  • Alex Baker (funded by Tenovus Cancer Care)
  • Sophia Tate (part funded by Wellcome ISSF translational kickstarter award)

I presently supervise the following undergraduate research projects

  • Elise Moses (PTY student, Aston University - "Developing targeted immunovirotherapies")

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

Mr Alexander Baker

Research student

Past projects

Recent successful project students from my lab include

  • Hei (Priscilla) Chan (year 3 Medic SSC student project - "Evaluation of chimeric adenoviral vectors and their potential to evade pre-existing anti-vector immunity in patient ascites").
  • Kamarl Rauf (Pharmacology project student - "Developing targeted virotherapies for pancreatic cancers").
  • Samuel Bannister (Pharmacology project student - "Manipulating the adenoviral fiber knob domain loops to probe receptor engagement")
  • Hanni Uusi-Kerttula (PhD, "Developing Ovarian Cancer Targeted Virotherapies" funded by Cancer Research Wales, 2014-2017, passed in 3 years with no corrections)
  • Jana Vanova (ERASMUS student, visiting from Charles University, Prague "Targeting of Ad10 to αvβ6 integrin")
  • James Moore (Intercalating Medical Student, "Development of visualisable virotherpies", 2016/17, passed with merit)
  • Sian Gardiner (MRes student, "Development of biotinylatable adenoviral vectors", 2015/16 passed with merit)
  • Tom Devonald (Pharmacology project student - "Effects of polycations and fusogenic peptides on adenoviral mediated cellular transduction" - passed with merit, 2013/14)
  • Mat Legut (PhD rotation project - "Development of adenoviral vectors targeted to EGFR")
  • Natalie Cox (BSGCT funded undergraduate Summer Studentship - "Development of Cancer Stem Cell Targeted Adenoviral Vectors" 2013 - selected to present findings as a poster at the BSGCT 2014 meeting")
  • James Campton (BSc (Med Sci) Clinical Medicine (First Class) "Development of Ad26 and Ad48 as gene transfer vehicles" (2012))
  • Heather Small (Wellcome Funded Summer Studentship: evaluation of Ad35 based vectors for cardiovascular interventions" (2011)
  • Ruth Parker  (MSc (Med Sci) Clinical Pharmacology (with Merit) "Gene Therapy for Cardiovacular Disease" (2012))
  • Pallavi Neogy  (MSc (Med Sci) Clinical Pharmacology (2011))
  • Brittany Durkin (MSc Biotechnology, "non-viral gene delivery systems" (2011))
  • Sophie Alizert (ERASMUS student, "Evaluation of novel adenoviral serotypes for cardiovascular gene therapy applications" (2010)).
  • Andrew Brown (BSc (Med Sci) Clinical Medicine (Upper Second) (2008)).
  • Kristeen Barker (BSc (Med Sci) Clinical Medicine (First Class) "Modulation of the Adenovirus serotype 5 capsid to preculde interaction with human factor X protein" (2007))
  • Jessica Doctor (BSc (Med Sci) Clinical Medicine (Upper Second) "Evaluation of an adenoviral pseudotype library for gene therapy applications" (2006))

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