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Rare Diseases Research
Newsletter of the Rare Diseases Translational Research Collaboration
Issue 14
August 2016
Of Collaborations and Consortia
Inside this issue
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Global Metabolomic
Profiling
HPO Workshop Report
Research Symposium 2016
Prof. Fiona Karet
Renal Theme Lead
Rare Renal Disease Day
Patient Day
“Think Research”
Eye Theme Update
Fellows’ Day 2016
Introducing a
RD-TRC Fellow
Data Pipeline
Data Co-ordinators
CRDN Summit 2016
Save the Date
Contact Us
In June, the RD-TRC completed a very successful week hosting Human
Phenotype Ontology (HPO) workshops across many of our disease
themes. We have received strongly positive feedback from the
participants, including Professor Peter Robinson from Berlin, and his
colleague Melissa Haendel from Oregon, who travelled to the UK to
help us in this endeavour. I believe many of you have established
links with Peter and Melissa to take HPO development forward in future
months. This is going to be enormously helpful when we come to
upload data relating to our deeply phenotyped cohorts onto the core
database.
The lead-up to the summer has been an exceptionally busy period,
not least because we have all been re-applying for support from NIHR
for Biomedical Research Centre status. We were very pleased to see a
section on the BRC form specifically asking about engagement with
the RD-TRC in the future. This is clearly an endorsement of the work
that we have been doing over the last four years, and places the
collaboration in a great position for future work on rare diseases.
Thank you for all who attended the workshops analysing metabolomic
data generated through the RD-TRC. We will be in touch in the near
future about a joint publication from our consortium which will
hopefully describe the impact of metabolomic analysis across the
range of diseases that we study. Clearly the phenotypic data that we
are collecting will be of major importance here. The data team will be
in touch in the near future for a data collection ‘push’ to enable a
high-impact output from the collaboration.
We look forward to seeing you at the Annual Conference in
September. I am pleased to say that Professor Paul Lasko will be
coming over from Canada to provide the keynote lecture. Have a
good break in the intervening period.
Prof. Patrick Chinnery
RD-TRC Co-Chair
Global Metabolomic Profiling
Providing new insights into the pathobiology of rare diseases
Until recently, existing techniques to assess metabolism were limited to a
very narrow approach, usually targeted to assess a single substance or
biochemical pathway. However, recent technological advances in the
field of metabolomics now permits assessment of thousands of
metabolites simultaneously. This provides a snapshot of the multiple
interconnected dynamic processes occurring in a tissue, organ or system.
It can be used to comprehensively assess the changes in metabolite
milieu that occur in disease, and also in response to a treatment. In many
areas of medicine, this technology has allowed previously unrecognised
metabolic derangements to be detected. Therefore, metabolomics may
provide insights which advance mechanistic understanding of diseases,
facilitate biomarker discovery and improve disease phenotyping.
Access to this technology has recently been provided by the NIHR Rare
Diseases TRC, using the Metabolon DiscoveryHD4™ platform. This
platform uses 2 ultra-high performance liquid chromatography methods
coupled with tandem mass spectrometry and a reference library of
>14,000 small molecules, allowing analysis of a large repertoire of
metabolites.
Access to Metabolon has allowed our group to assess the ‘metabolome’
in pulmonary vascular diseases, including pulmonary arterial
hypertension. Historically, this was considered a disease process localised
to the lung vasculature. However, it is now recognised that more
widespread metabolic disturbances exist, includes alterations in energy
metabolism and evidence that metabolic factors are implicated the way
that the right heart adapts to stress.
The metabolomics data in our patient cohort will be integrated with
genomic and clinical data as part of a deep phenotyping strategy.
Additionally, further analysis of metabolites and biochemical pathways of
interest may direct the search for new disease specific biomarkers.
Similarly, these applications will be relevant to many other diseases and
will continue to provide new insights into disease pathobiology in the
future.
Dr. Kasia Zalewska, Research Fellow
Pulmonary Vascular Diseases Unit, Papworth Hospital, Cambridge
Rare Diseases Translational Research Collaboration Newsletter; Issue 14, August 2016
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HPO Workshop – Rachel Spring Reports on
The Human Phenotype Ontology
About HPO
An ontology is a computational representation of a domain of knowledge
based upon a controlled, standardised vocabulary for describing entities
Peter Robinson
and the semantic relationships between them. It enables the linkage and
integration of datasets. Each term in the HPO describes a phenotypic
abnormality. Terms are ordered into a hierarchy of relationships.
Peter started work on HPO after starting using the London Dysmorphology
Database, "I had 20 search terms but still over 200 candidates, I then
added one or two more terms and the results went to zero. The search just
could not cope with ‘fuzzy’ and inexact matches" you needed a structure
for similar terms and grouping terms into families, which could be
matched. This characteristic became ore important when you compare
species.
The HPO terms are species neutral - this is important. Only 20% of the
20,000 genes are explained by phenotypes in humans; add in mouse
models and other species and over 80% of the genes have a phenotype
target. As you try and understand each individual’s genome you find
around 100,000 variants of which perhaps 40,000 match gene targets,
95% of these can be explained by common variants leaving around 500
changes that could be of interest. This combined knowledge is especially
important for rare diseases as it can trim this long list of 500 to a smaller list
capable of identification in small patient groups.
Developing the HPO
Most of the terms in the HPO have come from medical literature,
Orphanet, DECIPHER, and OMIM. HPO currently contains approximately
11,000 terms (and is still growing) and over 115,000 annotations to
hereditary diseases. The HPO also provides a large set of HPO annotations
to approximately 4,000 common diseases. To be a valid clinical tool,
Peter, Melissa and their teams, are collaborating with experts and
specialist medical communities across many countries to make the
ontology as robust as possible.
The RD-TRC workshops were intended to improve the understanding of
rare disease specialists in the UK and encourage investigators to become
part of the community effort. As the breadth and depth of annotation
grows, tools will be developed to improve diagnostic rates, share the
expertise of specialists with non-specialists, and improve the
understanding of rare diseases to benefit those suffering from them.
Things to come
As the ontology matures, there are several challenges the team hopes to
address in the future. For example, the development of HPO for common
diseases where there is a lifestyle or environmental aspect, for example
alcohol use or toxin exposure. This is an active research programme using
GP data where case notes will automatically be converted into HPO
terms for population studies.
(Cont. p. 4)
Peter trained as a physician
and studied maths and
computer science. As a
paediatrician at Charité in
Berlin, he developed an
interest in molecular
genetics and
bioinformatics. He began
developing the HPO in
2007 and it has been a
decade-long labour of
love.
He is due to move to the
Jackson Laboratory for
Genomic Medicine in
Connecticut in August.
Melissa Haendel
Melissa is an Associate
Professor at the Oregon
Health & Sciences
University.
Her background is in
developmental molecular
neurobiology but driven by
the ambition to make
better use of the plethora
of under-utilised data, she
has developed an interest
in ontologies and semantic
data integration projects.
Rare Diseases Translational Research Collaboration Newsletter; Issue 14, August 2016
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Contributing to the project
Peter and Melissa see the work being
done to improve the terms and their
relationships in the ontology as crucial
to the ultimate power of the tools they
are creating such as the phenomiser,
exomiser, genomiser and others.
While it is ‘under the bonnet’ work that
ultimately will be unseen, it will not go
unappreciated or even unattributed.
They are very happy to name
contributors in publications and on the
websites.
What to contribute
All feedback is valuable!
No one would be more delighted than
Peter and Melissa if you decided to
lock yourself and colleagues in a room
for a week to map the ontology for
your whole Theme.
RD-TRC HPO Workshop Report
(Continued)
There is also a big project looking into cancer funded by the
National Cancer Institute in the US. In cancer there is a good
thesaurus of terms from which the clinician can recognise the
cancers, but it is a long way from a biological ontology, it has
features of the disease but the disease may have multiple
expressions across different body systems.
The team is also looking to integrate the tools available and to
spending some time with ‘user friendly designers’ to improve the
experience and make it more intuitive for the non-geeks.
Tour of the Tools
Monarch’s Phenotype Profile Analysis page allows you to search
by phenotype(s).
But even if it were just a case of
commenting on the terms relating to
one disease this would be very
valuable and welcome work.
How to contribute
Once you’ve viewed the ontology and
reviewed the relevant terms and
relationships, these are the options for
letting the team know your comments
or suggestions for revision:
•
Melissa’s created a shared
spreadsheer for comments arising
from this workshop - select the right
tab for your Theme:
https://docs.google.com/spreadsheets/d/1yzjR1sxWYuCzXCnHK2EwXc41GUsmBOm6wQI-PWIkT0/edit#gid=1641274682
•
Peter’s HPO Tracker (register for a
login first) is a public mechanism for
comment:
https://github.com/obophenotype/human-phenotype-ontology/issues
The Exomiser is a Java program that finds potential diseasecausing variants from whole-exome or whole-genome
sequencing data. Starting from a VCF file and a set of
phenotypes encoded using HPO it will annotate, filter and
prioritise likely causative variants.
http://www.sanger.ac.uk/science/tools/exomiser
PhenIX is an exome analysis tool that utilizes phenotypic similarity
of diseases associated with the genes harboring candidate
variants to the phenotypic profile of the individual being
investigated.
http://compbio.charite.de/PhenIX/
Viewing the ontologies for purists
There are various ways to navigate the
ontology. Here are two:
Via HPO: The HPO can be viewed and
searched via the HPO website’s tools
section or directly via this link:
http://compbio.charite.de/hpoweb/showterm?id=HP:0000118
Via Ontobee: The Ontobee website
contains many ontologies, the link to
the HPO is here:
http://www.ontobee.org/ontology/HP
The Monarch Initiative aims to provide easy-to-use tools to
navigate this data landscape, services for other resources, and
educational outreach regarding the production of structured
data for biomedical discovery.
https://monarchinitiative.org/
The Patient Archive is a platform for patient data management
and collaborative diagnosis. It allows for text mining of clinical
summaries for HPO terms. And for consented patients, data can
be shared and exchanged to enable diagnosis and clinical
discovery.
http://patientarchive.org/#/home
Rare Diseases Translational Research Collaboration Newsletter; Issue 14, August 2016
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RD-TRC HPO Workshop Report
So what did we learn?
At the heart of the work of the RD-TRC lies the development of a national
federated database for in-depth phenotyping. Underpinning this work is
the adoption of HPO as the informatics scaffolding for data collection. In
medical informatics there are multiple classifications and ontologies that
have been developed and the workshop helped address why HPO was
chosen.
The workshops with Melissa and Peter were a very real ‘road test’ of the
importance of HPO to our work. As different projects led different
discussions on the use of HPO it became clear that the underlying HPO
framework could contribute to across the board. Each presentation
starting with an HPO outline of the latest developments: Tools that
supported the capture of ‘full’ patient profiles, links and look-up to different
disease databases and the integration of genomic and other data, often
across species. For the Rare Diseases Peter did the maths …
Dr. Roger James
RD-TRC IT Director
“There are a few hundred thousand variants across the human population,
of these perhaps 40000 are in the target region and from these around 95%
can be eliminated as common variants, you are still left with a long list of
perhaps 500 candidates which could be of interest. For the Rare Diseases
where patient numbers are small this is a statistical challenge. Perhaps 20%
of the 20K genes are associated with a phenotype in humans, but this goes
to 80% if you include all animal species”.
In introducing HPO Melissa and Peter explained how the HPO worked as a
framework for the identification and comparison of disease aetiologies. The
idea of HPO is that it functions as a biology based computation scaffold
which enables other ontologies to be integrated and searches to be
extended [see the comments earlier in the report on the problems of
search]. The introduction also gave a glimpse of the future - funded
developments in re-coding the existing cancer ontologies into the
biologically structured concepts of HPO and a major study in auto-coding
HPO terms for the common diseases from existing medical records.
The workshop was an interesting ‘road test’ of HPO and its use in the RDTRC. In some disease areas the use of HPO was well established and
mature, the Eye Diseases are the example here where scientifically and
metaphorically the organ is easy to observe and dysmorphologies well
structured and characterised. This is in contrast with the Central Nervous
System Disorders where the characterisation of disease is less obvious and
where cross species models are difficult to develop.
For some diseases, including Cancer and Respiratory, the source of the
disease is a combination of the organ susceptibility and some
environmental challenge. Understanding the patterns of the disease also
requires knowledge of the environment. Early days here but the big
developments in cancer encoding and integration of primary care records
will require the development of the ‘environmentalome’ - or the
characterisation and encoding of the challenge factors which will be the
path to a breakthrough.
For Skin and Musculoskeletal existing speciality disease classifications are in
widespread use. The work here is to extend HPO to make use of these
standards. Of importance here is the ‘openness’ of the HPO to incorporate
other ontologies, for example the cross species skeletal ontology Uberon,
this re-uses existing work but also integrates multiple studies. Both theme
explored how their existing ontologies could be ‘welded’ into HPO.
The ontology allows us to combine
data from different species and
different descriptors
Rare Diseases Translational Research Collaboration Newsletter; Issue 14, August 2016
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RD-TRC HPO Workshop Report
So what did we learn? (Cont.)
Other themes, such as Cardiovascular and Paediatrics, were
interested in how HPO could help deliver the bio-informatics
frameworks for further analysis. Here help was requested for the
conversion of ICD codes into HPO (various tools are available!)
and there was also interest in the ‘Phenogrid widget’ to identify
possible causative genes based on Phenotype patterns. In what
is best described as a ‘Mexican wave’ of views the potential is
significant and it hoped we could contribute to the feedback to
develop the idea further particularly in the development of
some filtering options.
For Immunology the discussion was around where HPO fits
alongside the collection of clinical data, for example
Immunology makes use of a large battery of lab tests that do
not fit neatly into a biological ontology. Aside from helping
refine and extend the HPO ontology the consensus was whilst
HPO is central to the structuring and integration of disease
descriptors it is not always the best approach for clinical data
collection. Conversion and mapping [the service provided by
the RD-TRC data coordinators] is an integral part of the research
work.
While human readers best understand data
that is provided as free text, computers can
better analyze data that is represented with
ontologies. In order for computers to learn how
free text corresponds to ontologies, a text
corpus (such as the HPO corpus) is required,
based on which a computer can learn this
relationship. Credit: Tudor Groza
To make use of all the data you need
something more than just search
For Haematology and Renal the conversations were around
how the HPO could be refined with the findings from the latest
research work. Current work, which uses the HPO to increase the
statistical power for gene discovery, was referenced. Our
discussion was around the easy to use service, offered by Peter
& Melissa, to add new terms to HPO via the GitHub tracker.
As an informatician [HPO geek!] I was excited by the technical
services (such as BioLark for term extraction from medical
records), the integration of different ontologies and the 5 star
tools to measure the quality of phenotyping (and the observed
improvement to phenotyping depth & coverage). The future
developments are also ones to watch – the developments of
patient entered phenotype data (lay persons synonyms), the
‘matchmaker’ & ‘phenopackets’ initiatives for the sharing of
phenotypic data and the integration with care systems (such as
Open.EPIC).
Our thanks to Melissa and Peter for what was a tremendous and
informative week for all attendees. We intend to work closely
with them in the future and also to keep everyone aware of their
latest developments. We start this with the HPO resources & links
document, which will be made available on the web [available
at http://rd.trc.nihr.ac.uk/news-and-events/hpo-workshops-june2016/]
Dr. Roger James
RD-TRC IT Director
Rare Diseases Translational Research Collaboration Newsletter; Issue 14, August 2016
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RD-TRC Annual Research Symposium
15th September 2016, Cambridge
If you have been invited but still need to register please follow this link:
http://www.profbriefings.co.uk/rdtrcsymposium2016/index.html
Rare Diseases Translational Research Collaboration Newsletter; Issue 14, August 2016
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Focus on Professor Fiona Karet
RD-TRC Renal Theme Lead
Nicola West Reports
Professor Fiona Karet, our Renal Theme Lead, is one of the world’s
leading researchers in rare kidney disease.
But it very nearly didn’t happen; early on in her career, Prof. Karet had
believed she would become a medical educator.
And then three things happened. Firstly, the medical graduate from
University College London, who had come to Cambridge in 1990 as a
registrar, was awarded a fellowship from the National Kidney Research
Fund (now Kidney Research UK) and began a PhD, where she
characterised what was then a little-known protein in the kidney,
endothelin.
Prof. Fiona Karet
Renal Theme Lead
Secondly, Prof. Karet came across a family in her weekly clinic who had
difficult hypertension (high blood pressure) which was clearly inherited;
not only was it passed from generation to generation but it was also
associated with the early death of an uncle at just 29 years from a stroke –
one of the primary signs of a particular type of inherited hypertension.
And thirdly, Prof. Karet attended an American Society of Nephrology
(ASN) conference in Boston, where she heard Professor Richard Lifton
from Yale University School of Medicine present on a new rare genetic
cause he had discovered for familial hypertension, and the specific
treatment that would normalise blood pressure.
Prof. Karet said: “I asked if he [Prof. Lifton] could analyse a blood sample
from the family to see if they had the same mutation he had spoken
about, which would explain their high blood pressure.
The advantage of knowing a genetic cause of something that is handed
down from generation to generation is that you can test family members
at risk of the same condition; they can then modify their treatment and/or
their lifestyles to minimise harm.
Prof. Lifton confirmed that the family did indeed have the mutation and
we changed their treatment immediately to something unusual but
known to work well. By this time I knew I wanted to learn how to do
genetic studies and to discover genes.”
With Prof. Lifton’s help Prof. Karet was awarded an intermediate fellowship
from the Wellcome Trust for post-doctoral training in his Yale laboratory,
which also gave her the opportunity to develop her own project. This
focused on acid-handling by the kidney, rather than salt-handling (which
is what underlies most of the blood pressure disorders), and she solved
genetic puzzles in a rare inherited acid-handling disorder of the kidney.
Prof. Karet said: “Your kidneys are like a washing machine, cleaning your
blood day in, day out. When they start to fail, you will fall very ill and
come under the care of a consultant – eventually most will need dialysis
or a transplant.
But the kidneys also play vital a housekeeping role, balancing the blood’s
salt and acid (and other small molecule) levels. It is this ‘housekeeping’,
and what happens if it goes wrong, which remains the focus of my
research.”
(Continued on p. 9)
Rare Diseases Translational Research Collaboration Newsletter; Issue 14, August 2016
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Professor Fiona Karet (cont.)
On her return to the UK, Prof. Karet was awarded a senior fellowship from the
Wellcome Trust and opened her laboratory in the Cambridge Institute for Medical
Research, where over the past 18 years her research team has moved from
discovering a genetic disorder to trying to understand what that means in terms of
physiology.
Clinical service
In 2005 Prof. Karet developed a multi-disciplinary clinical renal service in the hospital,
including a clinical geneticist and urologist. The clinic looks after patients with inherited
kidney disorders up until the point where they need dialysis or a transplant: “While their
kidneys are still working I will be the person responsible for them in my clinical service.
We’re very keen to provide advice to families of patients with genetic disorders, as
they may also be at risk of the same condition. We can advise them on how they can
manage lifestyles and diet, and often, offer a genetic test to give a yes/no answer to
the question of risk.
It’s very difficult having a rare disease, because you often feel as if you are the only
person in the world who’s got it, so we find that people generally are very receptive to
the engagement we offer them.”
On alternate weeks the team sees patients with kidney stones who might have
heritable disorders: “The urologist removes the stones and tells me what they’re made
of, and we can then think about why the patients made them in the first place.
Research
“Research is fundamental to our service; we aim to recruit all our patients for potential
research and where applicable encourage them to sign up to RaDaR [the National
Registry of Rare Kidney Diseases]. We carry out a variety of clinical research with a
different patient groups, including polycystic kidney disease (PKD) and cohorts of
those with rarer disorders such as Gitelman’s Syndrome and UMOD (uromodulin)
nephropathy, an inherited progressive disorder that leads to kidney failure”.
From that work has come Prof. Karet's RD TRC-funded project on deep phenotyping
and disease progression in patients within UMOD nephropathy.
Industry collaboration
RD-TRC is funding this clinical project, while a related project funded by Kidney
Research UK and supported by a US company is looking at the basic science. The
company provides the reagent for the team to use in their cellular experiments.
Prof. Karet notes that working with industry is important: “Another interesting avenue
we are just starting to develop concerns measuring devices for patients with
electrolyte disorders, which would be open to commercial investment in the future.”
Patient involvement
Educating patients and clinicians is also important to Prof. Karet: “We have organised
a number of patient/family support days for Gitelman’s and PKD, where patients can
network with people who have the same condition and with doctors who have heard
of their condition and are interested in them – they really respond to this. There is
another day planned for October for Gitelman and Bartter Syndrome patients and
their families, which will be RD TRC-funded.
“The team is closely involved with the Patient-Led Research Hub at the Cambridge
Clinical Trials Unit, with RaDaR and various patient-led groups.
“Some of my patients have started fundraising to support our research and education
activities.
“It’s also important to educate providers of care and in July we held a rare renal
disorders education day for people working in the multi-professional healthcare
team.”
(Continued on p. 10)
Rare Diseases Translational Research Collaboration Newsletter; Issue 14, August 2016
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Professor Fiona Karet (cont.)
The internet means that Prof Karet receives pleas for help and advice from patients all over the world: “I
can’t help them directly because they are not my patients, but I’m always very happy to talk to their
doctors and share experiences and knowledge of rare renal disorders – or their doctors are welcome to
refer them!
Funding landscape
“The NIHR has done a fantastic job in recognising how important rare diseases are, because if you add up
all the rare disease patients then you come to the equation that rare is common.
“Unfortunately money is limited and post-BREXIT I’m afraid to say that the funding landscape is presently
looking less certain. But we mustn’t lose sight of the fact that the healthcare professions and the research
community are international – science should be global and it should be collaborative.”
Rare Renal Disease Day
An Account by Kathryn Irons
On Friday July 1st 2016, Cambridge University Hospitals was host to 25 junior
doctors and allied health professionals for an inaugural “Rare Renal Disease
Day”. The day was designed to increase attendees' knowledge of rare renal
conditions, and highlight advances currently being made and the importance
of research.
The day began with an informative talk from Professor Fiona Karet (RD-TRC
Renal Theme Lead), highlighting lessons learned directly from patients with Rare
Renal Disorders. Following on, Dr. Patrick Deegan (Addenbrooke's) gave an indepth presentation about Fabry’s Disease and how it affects the kidney. Fabry’s
has very identifiable physical features and the audience examined how more
educational events aimed at GP’s could help spread awareness and improve
the speed at which patients are referred to hospital.
Kathryn Irons,
Theme Co-ordinator,
supports Prof. Karet and the
Renal Theme in the RD-TRC.
If you have any questions
regarding the Theme,
please contact her via
email:
[email protected]
After lunch, the audience was rewarded with an interesting and excellently
presented talk about The Risk and Management of Thrombotic
Microangiopathies (TMA) in the Organ Transplant Setting. Dr. Nick Torpey
(Addenbrooke's) conveyed very complicated subject matter in a clear,
concise way, allowing audience members unfamiliar with the area to follow the
talk. Next, Dr. Danny Gale (UCL, Renal GeCIP Lead) provided a fascinating
insight into Genomics and its future importance in helping to diagnose kidney
disease. The day concluded with Dr. Tal Munir (Leeds) speaking on CKD in
another ultra-rare rare disorder, paroxysmal nocturnal haemoglobinuria.
Susana Borja Boluda, Addenbrooke's Rare Renal Research Nurse said
“The day was very informative and interesting; a particular highlight was
Professor Karet’s presentation at the start of the day. The location was good,
the presenters were very approachable and friendly and there was lots of
opportunity for discussion”.
Carol Grenz, Living Donor Renal Transplant Coordinator added,
“This was an informative day, which highlighted to me the importance of
research in renal diseases, including in my specialist area. I learned that for
example, research findings indicate that a renal condition (thin basement
membrane disease) occasionally found in potential living kidney donors with
microscopic amounts of blood in their urine and previously considered
‘benign’, may have to be taken more seriously. We are constantly learning
more, moving forward in our understanding of rare renal conditions, developing
new drugs and changing our practice to improve the lives of renal patients.”
The day was co-sponsored by Alexion, Sanofi Genzyme and Shire.
Rare Diseases Translational Research Collaboration Newsletter; Issue 14, August 2016
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Patient Day aims to help those who want to
‘Think Research!’
Two NIHR organisations involved in rare disease research have joined forces to organise
a patient day, with the aim of involving patients more closely in their work.
Taking place in London on 12 October, the Think Research! Patient Day is the brainchild
of the NIHR Rare Diseases TRC and NIHR BioResource – Rare Diseases and is expected to
attract 100-120 patients and their representatives.
RD-TRC Operational Director Dr. Marijcke Veltman said: “Our aim for the day is to
provide a tangible benefit to patients that we can measure and by offering training,
which is free and relevant to patients interested in research, we believe we can achieve
this. We want to know if patients take away and then apply the learning from our
training to real-life examples; for example, have they joined steering committees,
reviewed protocols or patient information leaflets, or set up their own patient support
group website?
From a purely RD-TRC perspective we would also like to see patients get to meet
members of our Patient Advisory Group (PAG), and discover how they can liaise with
them. The PAG acts as a conduit for the patient voice to our Strategic Oversight Group
(SOG), and clearly the more patients who can be involved the more inclusive the PAG’s
messages will be. To get meaningful data we will follow all our patients for the next 12
months so we can track trends and then fully evaluate the day’s success and decide
whether it should be become an annual event.”
Free training
One of the big attractions of the day is the free training it will provide to patients.
Delegates will be able to attend two out of four training sessions, facilitated by
experienced trainers / advocates, over the course of the day, which will cover:
•
•
•
•
Ethics Committees
How to read study protocols
Patient Information Leaflets / Sheets
Running a successful patient group
Speakers
Speakers and facilitators include Simon Denegri, NIHR National Director for Patients and
the Public in Research and Chair, INVOLVE, and Alastair Kent OBE, Director of Genetic
Alliance UK and Chair of Rare Disease UK (RDUK).
RD-TRC co-chair Professor John Bradley (RD TRC) and BioResource – Rare Diseases
Director Professor Willem Ouwehand will give presentations on the future of rare disease
research and the diagnostic odyssey, while Dr. Robert Semple and Professor Lucy
Wedderburn will present on the metabolic and endocrine rare disease theme and
childhood myositis respectively. Professor Adrian Thrasher will provide closing remarks.
Expert Research Panel
Facilitated by Alastair Kent, this will open discussions to the floor, looking at some of the
research issues facing patients and support groups.
Finally, there will be the opportunity to network with other patient support groups over
lunch and discuss data and consent issues in greater detail with members of the RD-TRC
data team in the bespoke ‘data corner’ that will be set up on the day.
•
Think Research! Patient Day will take place from 10am-4pm, Wednesday 12
October, at the Barbican Centre, London. If you are interested in finding out
more please contact event organiser Georgina Norris T: 01223 254608 E:
[email protected]. You can also find out more about the day on our
website: rd.trc.nihr.ac.uk/think-research-patient-day/. Please note this event is
by invitation only and you are advised to contact Georgina if you are associated
with the two MINHR Organisations involved, would like to attend and have not yet
received an invite.
Rare Diseases Translational Research Collaboration Newsletter; Issue 14, August 2016
11
Patient Day Programme
A collaborative event between:
Rare Diseases Translational Research Collaboration Newsletter; Issue 14, August 2016
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Eye Theme Update
NIHR New Media Competition Winner
Congratulations are in order for RD-TRC funded investigator, Dr. Mariya Moosajee who was the winner of
the NIHR New Media Competition this year. The film entitled “Partnership for Sight” is narrated by and told
through the perspective of Matthew Murrell, a patient taking part in Dr. Moosajee’s research. If you would
like to view the video it can be found here: http://www.nihr.ac.uk/our-faculty/new-mediacompetition.htm
Matthew describes the condition he lives with,
choroideremia, and the change in vision that he has
experienced which will eventually result in complete
blindness. This research project has been taking skin
cells from patients and converting them to retina cells,
via initial conversion to stem cells, and investigating if a
class of small molecule drugs can change the ‘stop’
signal in the defective gene to a ‘go’ signal. Matthew
describes how taking part in this research has really
given him hope that others like him may not have to
face a future of complete blindness.
Mariya and her team with the Director of
Moorfields NIHR BRC, Professor Sir Peng Tee Khaw.
Left to right: Maria Toms, Dhani Tracey-White,
Mariya Moosajee, Peng Khaw, Rose Richardson &
Matt Smart.
The success of the study has enabled Dr. Moosajee to
embark on an industry collaborative study with PTC
Therapeutics and the RD-TRC, “Mapping the clinical
phenotype of Choroideremia to identify an optimal
therapeutic window for preventing sight loss – A UK multicentre deep phenotyping study”. Dr. Moosajee
explains: “Choroideremia is a blinding genetic eye disease, where children develop night blindness and
adults completely lose their vision. In order to progress from the laboratory to clinical trials we need to
investigate the natural history of this disease and identify the best time to provide treatment to halt or slow
the rate of sight loss”. The results of these studies may not only apply to patients with choroidermia but to
other ophthalmologic rare diseases such as retinitis pigmentosa, Lebers congenital amaurosis and conerod dystrophies.
PhD Secondment
In parallel, Maria Toms has received £5,000 from the RD-TRC Eye Theme towards an international PhD
secondment to the German Cancer Research Centre (DKFZ) in Heidelberg. Maria’s PhD involves
characterising the retinal phenotype associated with USH2A, the most common causative gene
associated with Usher syndrome, using various models including induced pluripotent stem cell derived
retinal cells from affected patients. She is also focused on developing the use of non-viral gene therapy as
a potential safe and therapeutic gene delivery strategy. Dr. Richard Harbottle leads the DNA Vector
Research group at DKFZ and has expertise in generating novel next-generation DNA vectors, particularly
the S/MAR vector system for in vivo application. During her time in Dr. Harbottle’s lab, Maria will learn the
techniques involved in the production of these vectors and will generate USH2A-containing S/MARs that
can be experimentally tested in an USH2A human cellular model to assess their safety and efficiency.
S/MAR vectors offer great potential in providing treatments for many different rare genetic disorders that
are due to the mutation of large genes.
Patient Day
Professor Graeme Black has started work on a patient day to be held in the autumn. ‘Rare Eye Disease
Day’ will bring together patients and researchers from across the UK, showcasing updates on NIHR funded
therapies and research on their associated conditions. In addition, patient focus groups will have their say
on barriers to participating and being involved in research. Watch this space for more news and
information.
To register interest in the event please contact Theme Co-ordinator Kathryn Irons by email,
[email protected], or telephone, 01223 245605, for more information.
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RD-TRC Fellows’ Day 2016
The RD-TRC held its second Fellow's Day on
July 26th, 2016 at Trinity Hall, University of
Cambridge. The event was held to welcome
our five newly appointed fellows to the larger
team of researchers and staff. The day
included a team building exercise for the first
half of the day, which allowed the new
fellows, the experienced fellows and RD-TRC
support staff, to network and build contacts.
The evening began with Professor Tim Barrett,
Paediatric Theme Lead for the RD-TRC,
addressing the fellows with poignant advice
on how to develop your career in rare
disease research and recounted some of his
triumphs and stumbles along the way. Our
Strategic Oversight Group, patient
representative, the distinguished Alastair
Kent, OBE, and Director of Genetic Alliance
UK, discussed “Capturing the Patient
Expertise in Translational Research” and
stressed the importance on involving patients
in research design and the benefits it.
The evening included two talks by RD-TRC
fellows who have been working on RD-TRC
funded studies for the past two years. Dr.
Ethan Sen, fellow in the Paediatric Theme,
discussed steroid resistant nephrotic
syndrome, his national cohort and the
potential biomarkers he is aiming to define.
Dr. Pedro Machado, fellow in the Muscle and
Nerve Theme, presented an overview of his
research programme in “Inclusion Body
Myositis”.
The reception to the Fellow’s Day has been
very warm. Our feedback has been
extremely positive and most fellows hope
that we hold this event annually. We
conducted a post event survey and
requested feedback on the event itself and
what fellows would like to see in the future
from the RD-TRC. As a result, we are hoping
to provide some additional courses that will
address the gaps in research knowledge for
some of the newer researchers. In the interim,
Theme Co-ordinators and Data Co-ordinators
are available to all fellows and researchers to
offer hands-on help with document creation,
ethics submissions, IRAS applications, HRA
approval, so please get in contact if anything
comes up.
Yvonne Kamieniecka
Senior Theme Co-ordinator
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RD-TRC Fellows
Introducing RD-TRC Research Fellows
Dr. Christos Tziotzios
Theme:
Skin Diseases
Supervisors:
Prof. John McGrath
Location:
King’s College Hospital, London
Project:
Frontal fibrosing alopecia (FFA) is a highly distressing
rare skin disorder associated with inflammation,
scarring and irreversible hair loss. It is a rare disease
affecting almost exclusively women, with an overall
population prevalence of less than 1 in 10,000.
The cause of FFA is unclear but there is evidence for a genetic
contribution because it can run in some families. This project aims to
discover the gene abnormality that causes FFA and what can be
done to improve treatment or prevent the disease.
Dr. Tziotzios will whole exome sequence a subset of participants
alongside deep phenotype collection to draw genotype-phenotype
correlations associated with the disease. A number of samples from
this project were also sent for metabolomic analysis under the RDTRCs on-going collaboration with Metabolon.
It is hoped this study will identify the causative genes of FFA and
provide novel insight into important pathways involved in scarring,
fibrosis and epithelial cell destruction.
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The RD-TRC Data Co-Ordination Team
Data Pipeline
The Rare Disease TRD is continuing it’s objective in developing a rare disease database, and we are
hoping to gain speed with the induction of two new data coordinators. Our new starters, John Li and
Kimberley St.John-Green have joined mid-July and have already embedded themselves well into the
team. We are currently advertising for a third Data Coordinator and are looking to recruit by the end of the
summer. The new staff are currently undergoing training and sharing their skills with on-going studies.
Our major obstacle in obtaining data from our studies appears to be a result of maintaining steady contact
with the study teams. The Fellows Day held on 26th July was a step towards bridging gap. The day was both
a fun and enriching experience for staff and fellows alike. The interactive activities helped to establish a
better communication channel between the fellows and data coordinators, alike. We are hoping to follow
through with further conversations with the fellows and to continue with regular updates regarding the
studies.
We have now gone live with 2 studies, (PaCiFy and PhenoDM1) and are hoping to follow shortly with the
Childhood overgrowth disorders (POD) study. We’ll be contacting our newly appointed fellows soon, to
begin the setup process of their studies in OpenClinca.
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Introducing New Data Co-ordinators
We would like to introduce two new members of the Data Team, here to help
include in-depth phenotypic data into the OpenClinica database.
John and Kimberley will work with investigators to design data plans and clinical
record forms as well as facilitate the data inclusion.
Welcome John and Kimberley!
John Li
Data Coordinator
Tel: 01223 254627
Email: [email protected]
John has a BSc in Computer Science and MSc in
Computer Graphics and has previously been working
the games industry as a games designer. He has been
the NHS for just over a year as a Data Coordinator for
Addenbrooke’s Paediatric Oncology & Haematology
research team and has now joined the RD-TRC team
Cambridge.
in
in
at
Kimberley St John-Green
Data Coordinator
Tel: 01223 254627
Email: [email protected]
Kimberley received her Master’s degree in Chemistry
from the University of York. She has worked in the
Pfizer Institute of Pharmaceutical Materials Science
modelling powder formulation for inhalation devices.
Followed by working as a laboratory technician and
administrator for Total Scientific Ltd., a contract
research organisation at Babraham Research
Campus. She has now joined as a clinical data
coordinator at the RD-TRC.
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Cambridge Rare Disease Network (CDRN)
Rare Disease Summit 2016
The Cambridge Rare Disease Network (CDRN; an organisation not
formally linked to the RD-TRC) is hosting its second rare disease summit
on 25 October in Cambridge.
The summit will bring together international leaders in rare disease
research and local experts to bridge the gap between research,
industry, business and patient groups.
The one-day conference will explore:
•
•
•
What can Cambridge contribute to global efforts in rare
disease research?
Who’s leading the way in collaborative, innovative research,
treatment and care for those with rare diseases?
How can we put patients and their families at the centre of all
discussions?
Confirmed speakers include:
•
EURORDIS CEO Dr. Yann Le Cam
•
Ben Howlett MP
•
Professor Patrick Maxwell, Regius Professor of Physic and Head
of the School of Clinical Medicine of the University of
Cambridge
•
Alastair Kent OBE, Genetic Alliance and Director of Rare
Disease UK.
Tickets for the CDRN Summit are now on sale through Eventbrite. To
find out more visit:
Eventbrite: eventbrite.co.uk/e/cambridge-international-rare-diseasesummit-2016-tickets-24888724846
Facebook: facebook.com/events/253880221626778/
Website: camraredisease.org
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Forthcoming dates
RD-TRC Research Symposium – II
15th September 2016
Trinity Hall, Cambridge
Email: [email protected]
Strategic Oversight Group - Meeting Dates
10th October 2016
10:00 – 15:00
RD-TRC Offices, Level 5, Barton House, Cambridge Biomedical Campus, CB2 0QQ
RD-TRC & BioResource Rare Diseases
THINK RESEARCH! Patient Day
12th October 2016
The Barbican Centre, London
10:00 – 16:00
A joint event with the NIHR BioResource - Rare
Diseases to promote rare disease research and
relevant research training to patients and their
carers.
Four training facilitators will provide hour-long training
slots on different aspects of taking part in research.
Simon Denegri, NIHR National Director for Patients &
the Public in Research and INVOLVE Chair, and
Alastair Kent, OBE, Director of Genetic Alliance UK,
are keynote speakers.
Email: [email protected]
Patient Advisory Group Meeting Dates
16th November 2016
10:00 – 15:00
NCVO, 8 All Saints Street, London N1 9RL
Theme Leads Meeting Dates
16 November 2016
13:00 – 16:00
NCVO, 8 All Saints Street, London N1 9RL
20th February 2017
13:00 – 16:00
(Venue TBC) London.
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Forthcoming dates
Forthcoming dates
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Contact us
NIHR Rare Diseases
Translational Research Collaboration
Barton House
Level 5, Box 406
Cambridge Biomedical Research Campus
Hills Road
Cambridge CB2 0QQ
UK
Tel: 01223 254601
Website: http://rd.trc.nihr.ac.uk
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