Chiara Bacchelli

Section Head

Dr Chiara Bacchelli


Experimental & Personalised Medicine
UCL Great Ormond Street Institute of Child Health
30 Guilford Street
London WC1N 1EH

Experimental and Personalised Medicine

Experimental medicine drives the translation of discoveries from basic science and clinical medicine into benefits for human health. The aim of experimental medicine is to identify mechanisms of pathophysiology or cause of disease and to demonstrate the validity and importance of new discoveries and treatments in patients. In a "From the bench to the bedside and back again" approach, the effective translation of results derived from experimental medicine will ultimately results in later phase clinical research and this in return will generate new hypotheses to be explored in the laboratory.

Personalised Medicine is the next generation of medicine and healthcare research with the potential to provide significant benefits to patients and effect strategic shifts in the way healthcare is delivered in the clinic. Personalised medicine uses an individual's genetic profile to guide decisions made in regard to the prevention, diagnosis, and treatment of a disease. Developing new diagnostic tests and expanding the use of biomarkers enabling the identification of the molecular cause of a disease will ultimately support the development of novel more precisely targeted treatments. It has been estimated that only 30-70% of patients respond positively to drugs. Stratifying in advance groups of patients who have a greater likelihood of responding to a particular therapy or avoiding adverse effects based on their unique genetic and environmental profiles is the aim of personalised (or stratified) medicine.

This section aims to blend together for the first time, experimental medicine with precision medicine approaches to deliver better, more targeted therapies to patients to ensure optimal responses.

Principal Investigators

Professor Phil Beales

Professor Phil Beales

Telephone Number:  0207 905 2277



Phil Beales is head of Genetics and Genomic Medicine at ICH, Director of the Centre for Translational Genomics (GOSGENE) and head of the Cilia Disorders Laboratory (CDL). His research interests centre on rare diseases, especially the ciliopathies, a class of disorders caused by defects in the formation or function of the cilium.

This focus on ciliopathies stems from a long term interest in Bardet-Biedl syndrome (BBS) a genetically heterogeneous disorder characterized primarily by retinal degeneration, obesity, polydactyly and renal malformations. Following his medical training at King's College and UCL, Phil was drawn to research, initially into the genetics of diabetes, insulin resistance and obesity. He became interested in BBS with the idea that understanding the pathomechanism of this rare disease may give broader insights into more common disease etiology. In 2003 the CDL was instrumental in establishing primary cilia dysfunction as causative in BBS, a finding that was at the spearhead of the now thriving field of ciliopathy research.

A wide array of disorders characterized by a diverse yet overlapping range of phenotypes have now been shown to stem from ciliary dysfunction. As a result the research interests of the CDL have broadened beyond just BBS and our research now encompasses how and why ciliary dysfunction leads to the range of phenotypes observed across the ciliopathy spectrum. The emphasis of the lab has recently shifted towards translational science and we are now actively engaged in ciliotherapeutics to define targets that could be exploited for treatment of these debilitating conditions.

Main Interests/Achievements

The Ciliopathies

Traditionally our efforts have been concentrated on understanding the normal cellular and developmental roles of cilia proteins and how collectively they give rise to the phenotypes observed. To this end we have developed several tools including modelling the diseases in cell lines and model organisms such as Danio Rerio and Mus Musculus. We also continue to closely study the human BBS phenotype and have previously reported on the genetic epidemiology, natural history, novel phenotypes, genotype-phenotype correlation, and the behavioural and neurological aspects seen in this disorder.

In the years following our work linking BBS to cilia many phenotypically similar diseases were also found to be ciliopathies. However research done in this lab was the first to show that some chondrodysplasias are also caused by ciliary dysfunction. The finding that mutations in  the intraflagellar transport (IFT) component IFT80 were causative in JATD has led to the discovery of a whole class of skeletal ciliopathies including JATD, the short rib polydactyly syndromes, Sensenbrenner/CED and Mainzer-Saldino. Causative genes have now been found for most of these, the vast majority of which also encode components of the core IFT complexes. Work to define precisely how and why defects in IFT lead to the skeletal phenotypes observed in this class of ciliopathies is ongoing.

We also work on a range of other areas related to the ciliopathies which include:

• The role of transcription factors in regulating expression of cilia proteins

• The biology of cilia formation and intraflagellar transport

• The relationship of cilia proteins to intracellular signalling pathways

• The relationship between the cilium and the cytoskeleton

Most recently we have begun focusing on establishing therapies for the ciliopathies. We are actively engaged in a range of projects encompassing both drug based and gene therapy approaches to try and find novel treatment options for these conditions.

3MC Syndrome 

3MC syndrome is a rare recessive disorder comprising characteristic craniofacial patterning defects including cleft lip and/or palate, learning difficulties, umbilical and distal limb defects.  We recently positionally cloned two genes, COLEC11 and MASP1 both of which encode proteins with key roles in the lectin complement pathway.  We demonstrated that COLEC11 has chemotactic properties that regulate cell migration such as the neural crest cells during embryogenesis.  This study links for the first time complement components with developmental disorders and indicates how we may come to better understand craniofacial development. 

Early-onset syndromal and non-syndromal obesity

We maintain a strong interest in the genetics of early-onset obesity largely through the study and understanding of single gene disorders. Our approach is simply that by gaining a greater understanding of the genetics and biology of rare disorders such as BBS, Alstrom, Cohen, Albrights hereditary osteodystrophy and MOMO to name but a few, we can apply the common biochemical pathways to the more complex disorders.


This gene discovery facility was established in 2010 to provide comprehensive novel mutation detection in patients with orphan diseases. GOSGENE is funded by the Specialist Biomedical Research Centre (GOSHICH) and will fund as well as undertake the experimental work required for individual PIs/clinicians from diverse backgrounds who may not have the relevant genetics expertise. We use a wide range of techniques including traditional linkage, autozygosity mapping and increasingly Next Generation sequencing. We also undertake detailed analysis of NGS datasets using dedicated bioinformaticians.


2014 - 2016 NIHR Translational Research Collaboration – Paediatrics Cross Cutting ThemeTitle: “Deep phenotyping in Bardet-Biedl and Alstrom Syndromes”, Award: Joint with Prof Tim Barrett (BCH) - £465,000
2013 - 2016 Dutch Kidney Foundation, Title: “Combatting juvenile kidney failure in renal ciliopathies”, Award: £314,993
2013 - 2015 NEWLIFE, Title: “Investigation of the role of the compliment pathway in 3MC syndrome and craniofacial development”. Award: £120,000
2012 - 2015 Wellcome Trust Strategic Award/MRC contribution. Title: Human Induced Pluripotent Stem Cell Resource (co-applicant). Award: £12m to Sanger Institute/KCL (Durbin/Watt)
2010 - 2015 EU Framework Programme 7 – SYSCILIA. Title: Systems biology of the cilium and disease. Award: EURO 529,000 

Recently completed grants

2012 - 2014 Wellcome Trust Senior Research Fellowship in Clinical Science. Title: “Investigating the role of primary cilia in development and disease”. Award: £332,000
2011 - 2013 NIHR (GOSH/ICH) Biomedical Research Centre. Title: Establishment of GOSgene – centre for gene discovery. Award: £565,000
2010 - 2011 NEWLIFE. Title: “Identification of two 3MC syndrome genes”. Award: £10,500
2009 - 2012 Medical Research Council. Title: “The role of cilia in development of hyperinsulinaemia and insulin resistance”. Award: £457,350
2009 - 2011 NEWLIFE. Title: “Defining molecular heterogeneity in ciliopathies”. Award: £119,998
2007 - 2012 Wellcome Trust Senior Research Fellowship in Clinical Science .Title: “Investigating the role of primary cilia in development and disease” . Principal investigator/fellow: PL Beales . Award: £1,530,000

Professor Lyn Chitty

Telephone Number:  0207 905 2876



I am in the unique position of being the only Professor of Genetics and Fetal Medicine in the UK, and was appointed to this chair at the Institute of Child Health, University College London in 2009; I am also a Consultant in the Fetal Medicine Unit at University College Hospital NHS Foundation Trust.  I have published extensively on prenatal diagnosis, and the ultrasound screening of fetal abnormalities, specifically fetal skeletal abnormalities, and was responsible for the creation of the fetal size standards now in use throughout the UK and beyond.  I was a member of the National Screening Committee on Routine Fetal Anomaly Scanning for some years.  I am also an editor of the journal, Prenatal Diagnosis, and have recently been elected to the board of the International Society of Prenatal Diagnosis.  I was recently been appointed as the Clinical Director of the NIHR Clinical Research Network: North Thames.

Main Interests/Achievements

My main current research interest is in non-invasive prenatal diagnosis and I leads a five-year Programme Grant from the National Institute of Health Research (Rapid Accurate Prenatal non-Invasive Diagnosis (RAPID) – an integrated project to refine and implement safer antenatal testing) which is designed to develop the standards for routine implementation of this exciting new technology. 

Grants (last 5 years/current)
2013 - 2015
NIHR Programme Grant for Applied Research (extension): Reliable accurate pre-natal non-invasive diagnosis (RAPID) - an integrated project to refine and implement safer antenatal testing - £271,195* (Chitty, Morris, White, Crolla, Kent, Lench, Farndon, Skirton, Hill, Fisher, Kroese, Wright, McEwan)
2013 - 2015
GOSH UCL BRC Industry Collaboration Grant. New approaches to next generation sequencing (NGS) of cell free DNA in maternal plasma - £63,717
2013 - 2017
Genome Canada and the Canadian Institute for Health Research. Personalised Genomics for prenatal Aneuploidy Screening Using maternal blood (PEGASUS) - £689,444. (Rousseau, Langlois, Chitty and 24 others)
2012 - 2012
GOSH/UCL Institute of Child Health Biomedical Research Centre (GOSH BRC). Development of rapid and comprehensive pre- and post-natal diagnosis of skeletal dysplasias - £29,020
2012 - 2014
Newlife Foundation for Disabled Children. Non-invasive prenatal diagnosis of specific genetic conditions: the micro-deletion syndromes - £115,660. (Raymond, Chitty, White)
2011 - 2012

Great Ormond Street Children’s Charity:

Prenatal congenital abnormalities - £381,126. (Scott, Chitty)

2011 - 2014
MRC/NIHR Efficacy and Mechanism Evaluation Programme: EACH Study: Evaluation of array comparative genomic hybridisation and non-invasive prenatal diagnosis using cell free fetal DNA in prenatal diagnosis of fetal anomalies - £1,6000,000 (Robson, Chitty, Morris, Graham, Wellesley, Fisher, Ambler)*
2011 - 2014

European Union: Genetic testing in Europe –

Network for the further development, harmonization, validation

and standardization of services (Eurogentest2) -

£58,049.00 (Matthijs, Chitty and 12 others)

2011 - 2013
SPARKS Project Grant: Prevention of neural tube defects by Inositol: The PONTTI Trial - £67,111) (Copp, Greene, Chitty, Mills)
2009 - 2014
NIHR Programme Grant for Applied Research: Reliable accurate prenatal non-invasive diagnosis (RAPID) – an integrated project to refine and implement safer antenatal testing - £2,053,811 (Chitty, Crolla, White, Lench, Avent, Westwood, Altman, Burton, Farndon, Soothill, Morris, Kent)*

Professor Stephen Hart

Professor Stephen Hart


Telephone Number: 0207 905 2228



After receiving my BSc in Genetics at Liverpool University in 1981, I spent most of the next ten years in South Africa, firstly at University of the Witwatersrand (“Wits”) and South African Institute for Medical Research (SAIMR) where I worked with Professor Trefor Jenkins on projects related to human genetic and evolutionary studies in the peoples of southern Africa. It was during this period, while studying for a masters degree in partial adenosine deaminase (ADA) deficiency, that I first became interested in the possibilities of gene therapy for genetic diseases. In 1987 I moved to the University of Cape Town Microbiology Department to develop my knowledge and skills of recombinant DNA technology, and, not to mention, beach life in the Western Cape! After graduating with my PhD in 1991 I joined the lab of Bob Williamson at St. Mary’s Hospital Medical School in Paddington, on my first postdoc project into gene therapy for cystic fibrosis, the gene for which had been discovered less than two years earlier. Three years later I joined the Institute of Child Health where my group continues to develop genetic therapies for respiratory diseases associated with cystic fibrosis and primary ciliary dyskinesias (collaboration with Chris O’Callaghan and Hannah Mitchison), siRNA therapy for neuroblastoma (collaboration with Andy Stoker), exon-skipping oligonucleotide therapeutics for Duchenne muscular dystrophy (collaboration with Francesco Muntoni) and recently siRNA therapies for skin diseases (collaboration with Wei-Li Di and Veronica Kinsler).

Main Interests/Achievements

Genetic therapies require a means of delivery of the therapeutic gene or oligonucleotide to cells of the affected tissue and this is perhaps the most important barrier to overcome in the development of gene-based therapies. Viral vectors are widely used and have had some major clinical successes but for some applications their immunogenicity limits their effectiveness for applications where repeated in vivo delivery is required. Thus, we have focused on the use of non-viral formulations since these are less immunogenic, have a wide range of packaging capacities, are safer than viruses and are more easily produced in scales required for clinical uses.

In our group we are developing multifunctional nanoparticles termed Receptor-Targeted Nanocomplexes (RTN) comprising mixtures of cationic liposomes (L) and cationic targeting peptides (P) which self-assemble, electrostatically on mixing with DNA (D) or siRNA (R). RTN formulations comprise a peptide, P, which packages nucleic acids through a cationic K16 motif and targets receptors through short peptide ligands such as RGD integrin-targeting motifs (Tagalakis et al., 2011). The liposome component of the RTN includes a neutral lipid, DOPE, which enhances transfection by destabilising the endosomal bilayer allowing releasing the nucleic acid into the cytoplasm after endocytic uptake of the nanocomplexes and before endosomal degradation can occur. Peptide and lipid chemistry allows a wide range of functionalities to be incorporated into the nanocomplexes so that these formulations increasingly resemble artificial viruses in their abilities to overcome cellular barriers to transfection. 


Recent developments of RTN formulations in our lab include the incorporation of contrast agents for real time imaging of biodistribution by MRI in brains (Kenny et al., 2013) and tumours (Kenny et al., 2013) and radiolabel incorporation for gamma scintigraphy imaging of RTNs in different regions of the lungs of pigs after nebulisation (Manunta et al., 2013).

RTNs for Neuroblastoma and Brain

We are developing negatively-charged (anionic) RTNs which are potentially less toxic and which show greater cell specificity of transfection than cationics. These formulations are in development for delivery of gene therapies in the brain (Tagalakis et al., 2014) and neuroblastoma therapeutics with siRNA (Tagalakis et al, ms in preparation).

Nanocomplexes containing siRNA have also been optimised for their in vitro transfection efficiency and biophysical properties (Tagalakis et al., 2013;2011), and have shown in vivo efficacy in brain, tumour and lung (ms’s in preparation).

CF and PCD Gene Therapy with Minicircle Vectors

Derivatives of nanocomplexes are in development for in vivo gene delivery to lung for CF (Tagalakis et al., 2008, Manunta et al., 2011;2013) and PCD gene therapy. We are also developing minicircle DNA for packaging into RTNs for gene therapy of CF and PCD as they lack the bacterial DNA backbone and so achieve higher levels of transfection than plasmid vectors both in vitro and in vivo.

siRNA Therapies for Brain and Lung

We have also developed specific RTNs for transfection of vascular tissues in rat (Meng et al., 2006) and rabbit models (Meng et al., 2013) achieving therapeutic efficacy in preventing neointimal hyperplasia.

Grants (last 5 years/current)

Great Ormond Street Hospital children's charity Leadership Grants (Ref V1298)

April 2013 - 31st March 2016
"Gene therapy for cystic fibrosis". £123,030

 Association for International Cancer Research (AICR, ref no. 12-1272) (PI)

July 2012 - July 2014
Collaborator Arturo Sala, ICH.  "RNA interference therapeutics for neuroblastoma"

Cystic Fibrosis Trust (Co-I)

Oct 2012 - Oct 2015
"In search of a drug to improve F508 CFTR channel function: development of a gating-sensitive fluorescent probe and compound library screening".  £101,590

Neuroblastoma Society (CO-I)

Sept 2013 - Sept 2015
PI Andy Stoker, ICH.  "Indetification of tyrosine phosphatases that suppress differentiation and promote survival in neuroblastoma cells".  £129,356

Children with Cancer UK and GOSH Children's Charity (Co-I) (Ref No: 2012-NAT-30)

Aug 2012 - Aug 2014
PI Andy Stoker, ICH.  "Comibination Treatments to Drive Neuroblastoma Tumour Differentiation and Senescene".  £134,488

Wellcome Trust (PI)

Sept 2011 - Sept 2014
Co-I R. McAnulty, UCL.  "Tropical delivery of siRNA to the airways with nanoparticles for therapy of cystic fibrosis".  £250,000

 Association Francais Contre les Myopathies (Co-I)

April 2011 - 31st March 2010
"Advances in Oligonucleotide Mediated Exon Skipping For DMD And Related Disorders!.  International MDEX Consortium - my role is in delivery systems for oligonucleotides.  PIs Francesco Muntoni, ICH, Matthew Wood and Kay Davies(Oxford).  Application Total £5,585,305 (£2,257,007 for ICH).  Awarded approximately 63% £3,518,742 (£1,421,914 for ICH).

CHRAT PhD studentship (PI)

Oct 2010 - Oct 2013
Mr. Mustafa Munye "Gene therapy for primary cilliary dyskinesia."  £60,000


May 2009 - 30th April 2012
Co Investigators Hailes, Tabor, Lythgoe (UCL), Lawrence (King's College London), Gill, Love (Bristol).  "Nanoparticles for the Targeted Delivery of Therpeutic Agents to the Brain for the Treatment of Dementias Collaboration with UCL chemistry, Kings College London, University of Bristol, North Bristol NHS Trust.  Total grant £2,040,038 of which £1,391,286 for UCL.

Technology Strategy Board/EPSRC/BBSRC (PI)

Feb 2008 - Jan 2010
Co-I J.McEwan, UCL. "Adjunct gene therapy for coronary artery bypass grafting".  Collaboration with Genex Biosystems Ldt and Ark Therapeutics Ltd. (£543,261; £232,042 for ICH)

Dr Dagan Jenkins


Telephone number: 0207 905 2838



The main focus of our lab is to investigate the pathogenesis and treatment of skeletal ciliopathies.

Cilia are microtubular protrusions present on the surface of most cells. Mutations that disrupt the function of cilia have been identified in many human diseases, and abnormal ciliogenesis is associated with a characteristic set of human phenotypes, the ‘ciliopathies’. At least 90 causative genes have been identified in ciliopathies, and collectively it is estimated that approximately 1 in 1000 people may be affected by this category of disease. These include a number of important human diseases such as renal cystic disease, obesity and retinal degeneration. Therefore, investigating the mechanisms of pathogenesis in relation to cilia has potentially broad implications for the treatment of a variety of important diseases.

A subset of ciliopathies, including Jeune, Carpenter and Sensenbrenner syndromes, feature particular skeletal involvement in addition to some of the classical ciliopathic phenotypes. These include abnormal development of the skull (craniosynostosis), rib cage and long bones. Unlike classical ciliopathies, these so-called ‘skeletal ciliopathies’ are typically caused by mutations in genes encoding ciliary trafficking proteins, including core components of intraflagellar transport (IFT) and vesicle transport machinery.

One of the main interests of our lab is therefore to investigate the mechanisms that regulate ciliary trafficking. Another active area of research focuses on neural crest cells (NCCs). There is growing evidence that skeletal defects, such as craniosynososis, cardiac malformations and neurological abnormalities/learning defects found in ciliopathies may be caused by abnormal specification, differentiation and/or migration of NCCs. We are therefore also actively exploring the mechanisms that regulate NCC development, and possible therapeutic manipulation of these cells.

Main Interests/Achievements

Investigating ciliary trafficking in the pathogenesis and treatment of ciliopathies

All types of cilia lack the necessary machinery for protein synthesis. Therefore, all proteins required for ciliary function must first be transported to the membrane and/or base of cilia in specific vesicles. As such, defects in ciliary trafficking lie at the heart of all ciliopathies. Our lab therefore focuses on the skeletal ciliopathies with a view to understanding the mechanisms that regulate ciliary trafficking and developing therapeutic approaches that may be more widely relevant to all ciliopathies.

Two complimentary approaches are used:

 1. Tandem-affinity purification (TAP) and SILAC are used to identify and characterise novel ciliary trafficking proteins, and gene knockdown/mutation in cell lines and model organisms is used to test the potential of manipulating ciliary trafficking for therapy.
 2. High-throughput microscopy-based small molecule screens are undertaken to identify compounds that target ciliary trafficking, and drug hits are tested for their therapeutic potential in cell lines and model organisms.

Targeting neural crest cell fates for the treatment of birth defects and tumours

Neural crest cells (NCCs) are multipotent cells that follow highly specific migratory paths to populate a number of tissues in developing embryos. They subsequently differentiate into a variety of cell types, including cartilage, neurons, cardiomyocytes and melanocytes. Growing evidence has suggested that cilia are present on the surface of NCCs and their derivatives, and that abnormal specification, differentiation and/or migration of NCCs contributes to skeletal and cardiac defects, as well as Hirschsprung’s disease, in ciliopathies. The hypothesis that we are currently testing is that factors that influence NCC identity or migration may be used for treatment of ciliopathies and other NCC-derived defects (including specific tumours).

Three specific approaches are used:

Chemical and genetic screening is undertaken to identify novel genes and FDA-approved drugs that influence NCC development in zebrafish embryos.
These factors are tested for their ability to treat skeletal ciliopathies (e.g craniosynostosis) in model organisms and to inhibit growth of NCC-derived tumour cell lines.
 3. Genes encoding key ciliary trafficking proteins are mutated specifically within NCCs in mice (using a Cre-lox approach), and resulting skeletal defects and other neurocristopathies are characterised.


Research Funding

11/13 - 10/16
MRC New Investigator Research Grant: Nudc as a new molecular target to investigate the pathogenesis and treatment of skeletol ciliopathies
05/12 - 10/12
UCL SLMS "Investing in Excellent Researchers" Award
02/11 - 05/11
Wellcome Trust ViP Award
04/07 - 03/10
MRC Project Grant: RAB23 mutations and insight into craniosynostosis

Dr Chiara Bacchelli

Doctor Chiara Bacchelli

Telephone Number:  0207 905 2108



I lead a group focused on Translational Genomics and Stratified Medicine at UCL Institute of Child Health within the Centre for Translational Genomics – GOSgene. Funded by the Great Ormond Street Hospital Biomedical Research Centre of the NIHR, GOSgene opened in February 2010 to facilitate rapid gene identification in uncharacterised rare genetic diseases as part of the ‘Molecular Basis of Childhood Disease’ Theme.

My work and interest in genetics began during my PhD working on rare congenital disorders with Professor Peter Scambler (Molecular Medicine Unit, ICH). I then worked with Professors Bobby Gaspar and Adrian Thrasher in the Molecular Immunology Unit (ICH) on the genetic characterization of primary immunodeficiencies. After a period at the Institute of Cancer Research working in the Section of Cancer Genetics lead by Professor Nazneen Rahman, I returned to UCL to facilitate the formation of GOSgene.

During the course of my career I have acquired a vast repertoire of molecular genetic techniques with focus on disease gene identification through linkage analysis, homozygosity mapping and next generation sequencing. My current work in GOSgene focuses on the use of exome and whole genome sequencing approaches coupled with advanced data analysis to deliver diagnostic tools for rare diseases. These will be tools for gene identification in affected individuals to help improve diagnostic testing, genetic counselling, family planning options, prenatal service development and personalised healthcare.

Main Interests/Achievements

My two main research areas of interest are rare diseases research and developing strategies for delivering stratified and precision medicine.

Rare Diseases Research. There are over 6,000 known rare diseases, often life-threatening or chronically debilitating. Collectively rare diseases are not rare and they affect 350 million people worldwide. In the UK, 1 in 17 people will be affected by a rare disease at some point in their life. This amounts to approximately 3.5 million people affected in the UK. 75% of rare diseases affect children and are often of genetic origin but only a quarter has a definitive molecular cause identified. Usually there is no effective treatment, but screening for early diagnosis, followed by suitable care, can improve quality of life and life expectancy.

The aim of my research in GOSgene is to accelerate the identification of yet unknown pathogenic genes in rare diseases by implementing the latest next generation sequencing technology. This research is critical to understand the pathophysiology and natural history of rare diseases, to identify potential therapeutic targets, discover new biomarkers, and ultimately adequately evaluate treatments and therapies.

Personalised Medicine is the next generation of medicine and healthcare research with the potential to provide significant benefits to patients and effect strategic shifts in the way healthcare is delivered in the clinic. Personalised medicine uses an individual's genetic profile to guide decisions made in regard to the prevention, diagnosis, and treatment of a disease. Developing new diagnostic tests and expanding the use of biomarkers enabling the identification of the molecular cause of a disease will ultimately support the development of novel more precisely targeted treatments. It has been estimated that only 30-70% of patients respond positively to drugs. Stratifying in advance groups of patients who have a greater likelihood of responding to a particular therapy or avoiding adverse effects based on their unique genetic and environmental profiles is the aim of personalised (or stratified) medicine.

Approaches implemented:

- Development of new diagnostic tests utilizing whole exome, whole genome or targeted gene panels sequencing

- Patient stratification strategies based on individual’s genotype

- Advance bioinformatics tools for big data analysis

- Identification of biomarkers for precision medicine implementation

- Integration of -omics data

- Development of companion diagnostic tests


Our research team GOSgene has thus far studied 179 families that are drawn from 62 different rare disease clinical phenotypes. Exome sequencing in >400 samples has been performed. A number of these projects are at present on-going but so far we have been able to identify 41 causative genes (66% success rate). Of these candidate genes, 24 (58%) are novel genes, never been described before to be associated with disease.

Grants (last 5 years/Current)
2013 - 2017 NIHR Biomedical Research Centre - Fellowship in Translational Genomics and Stratified Medicine awarded to Dr Chiara Bacchelli
2012 Daniel Courtney Trust Charity; Principal Investigators: N Shah, C Bacchelli. Project title: “Exome sequencing in patients with microvillus inclusion disease” 
2010 Biomedical Research Centre - Experimental research; Principal Investigator: K Gilmour, Co-investigators: HB Gaspar, C Bacchelli, N Lench, CN Cale. Project title: “Development of a next generation sequencing assay to screen children for twenty genes known to cause severe combined immunodeficiency (SCID)” 

Dr Rakesh Amin

Doctor Rakesh Amin




I am a clinical academic doctor at GOSH and ICH. I have a special interest in common and rare forms of diabetes, endocrine tumours, late effects and growth failure.

Qualifications and training

MBChB (with Honours), MRCP, MSc, MD with commendation, FRCPCH.

I received an honours degree in medicine (1991) from Leeds University, and trained in paediatric medicine in London (1996) before specializing in paediatric endocrinology and diabetes in London and Oxford (2004). 

I was awarded an MD with commendation for research undertaken at Cambridge on the subject of the hormonal determinants of microvascular disease in type 1 diabetes (2006). I have worked as a NHS consultant in paediatric endocrinology and diabetes, initially at the Royal Manchester Children’s Hospital (2005) and then at St Barts and the London Hospitals (2010) and started my current post in 2012.

I am a member of the British Society for Paediatric Endocrinology and Diabetes (BSPED) and the European Society for Paediatric Endocrinology. I am a member of the National Diabetes Audit Dataset Working Group, the BSPED Clinical Trials Study Group and numerous other study and research groups and was appointed as the diabetes officer for BSPED in 2013.

Main Interests/Achievements

My research training was in epidemiology and physiological mechanistic studies in the development of diabetes complications, in particular diabetic nephropathy. This included management of large datasets, analysis of longitudinal patient level data, insulin clamp studies, overnight hormonal profiles (and their analysis) and measurements of fat metabolism.

Currently my research interests are in three broad areas;

1. The Pathogenesis of Type 1 Diabetes (T1D)

  • Developing and validating a novel assay to measure serum Insulin methylated DNA as a Marker of Beta-Cell Death prior to and in early T1D and during T2D.   
  • In-vivo Imaging of Beta-cells and Insulinitis.
  • TRIALNET Pathways to Prevention of Diabetes Study. Role: Local PI.

2. Complications of Diabetes

  • The University College London Investigation of Diabetes (UCLID) Study is a long-term longitudinal study of the pathogenesis of diabetes complications and will involve sample collection (including DNA) for UCL Biobank. 
  • Developmental of a Cardiovascular Disease Risk Algorithm for T!D. This study is in collaboration with the Imperial College Public Health Research Department and will involve analysis of linked large datasets and evaluation of the use of this algorithm through e-health.
  • In collaboration with the Child Policy Research Unit (lead Prof Terence Stephenson), I am investigating outcomes in children with diabetes using data from the National Paediatric Diabetes Audit and linked datasets. These outcomes include acute and chronic complications, metabolic control and patient reported experience measures.
  • Effect of Ethnicity in T1D  
  • Brain Imaging in T1D
  • The Epidemiology of Diabetic Ketoacidosis in the UK 
  • Islet autoantibody status in children with diabetes.

3. Other interests

  • Paediatric HOMA - in collaboration with Dr Nathan Hill at OCDEM.
  • Long term Outcomes of Congenital Endocrine Conditions Using Primary Care Datasets; Congenital Adrenal Hyperplasia, Turners Syndrome, Congenital Hypothyroidism.

I am leading on creating an annual ICH postgraduate endocrine and diabetes symposium, am a clinical and educational supervisor in paediatric endocrinology and diabetes for trainee doctors and am a consultant appraiser.

Grants (Last 5 years/current)
2014 - 2017
UCL Impact PhD Awards. £32,583 per year for 3 years. Role: Joint PI
2014 - 2016
The NIHR Rare Diseases Translational Research Collaboration. £114,601.25. B-cell death in Type 2 diabetes. Role: PI
2014 - 2015
NIHR National BioResource. ~£200,000. The University College London Investigation of Diabetes (UCLID) Cohort. Role: PI
2012 - 2014
BSPED. £14.500. Long-term Outcomes for Women with Turner Syndrome. Role: PI
2012 - 2014
The Clinical Endocrine Trust. £26.700. Current Service Provision for Women with Turner Syndrome. Role: PI
2011 - 2015
Barts & London Charity. £399,900. The Barts and the London Paediatric Insulin Pump School. Role: PI

Dr Hannah Mitchison

Dr Hannah Mitchison

Dr Hannah Mitchison


Telephone Number:  0207 905 2866


Hannah Mitchison is a GOSHCC Reader in Molecular and Medical Genetics working on understanding the cell biological and genetic causes of children’s inherited diseases, through family studies and functional analysis in model organism systems. Her work is focused on recessive diseases caused by dysfunctions of cilia, and lysosomes. Originally trained in cancer virology, Hannah developed her interest in the molecular genetics of paediatric diseases during her work in the laboratory of R. Mark Gardiner on discovery of CLN3 and CLN1 gene mutations causing juvenile Batten disease, followed by a move to Robert Nussbaum’s laboratory at NIH to create a CLN3 knockout model. Returning to the UK to establish a research group at UCL, from 1999 she commenced studies with her long-term clinical colleague Eddie Chung into the genetics of ciliopathy disorders, centred initially on primary ciliary dyskinesia (PCD) and motile cilia disease. Hannah moved to the UCL Institute of Child Health in 2008, expanding her research to diseases of the sensory cilia in collaboration with Peter Scambler and Philip Beales, particularly skeletal ciliopathies including Jeune syndrome (Asphyxiating Thoracic Dystrophy). She co-directs the Cilia Disorders Laboratory with Philip Beales.

Hannah publishes and presents widely on ciliopathy disorders, serving as scientific advisor to the Ciliopathy Alliance and PCD Family Support Group, and as trustee of the Jeune Syndrome Foundation. She is an ICH Postgraduate Advisor, GGM Education Lead, Pathway and Module lead for the UCL Masters in Paediatrics & Child Health, and UCL and Module lead for the QMUL/UCL joint Health Education England Masters in Genomic Medicine. Current team members include Mitali Patel, Jane Hayward and Mahmoud Raafat.

Main Interests/Achievements

Our main research interests are the molecular genetic basis of cilia and lysosome diseases, and translational aspects moving towards the development of new treatments that an understanding of the underlying disease cell biology can offer. This work has led to significant improvements in diagnostics for affected individuals, and to a new understanding of the heterogeneous genetic and molecular basis of primary ciliary dyskinesia and Jeune syndrome following identification of >40 different disease genes for these two devastating conditions. Our work is supported by The Wellcome Trust, Action Medical Research, Newlife Foundation and GOSH Children’s Charity, and for PCD is made possible through long-term collaborative links to the UK’s PCD National Service (Claire Hogg, Amelia Shoemark, Jane Lucas and Christopher O’Callaghan).

The long-term aims of the research programme are: to understand how different clinical outcomes for ciliopathy patients arise from different genetic mutations; to characterise the interactome of proteins responsible for building and maintaining ciliary functions; and to translate our lab research to the bedside by development of new genetic-based therapies.

  • Genetic diagnostics for PCD, ciliary chondrodysplasias (Jeune Asphyxiating Thoracic Dystrophy) and related sensory ciliopathies. Funded by GOSH Children’s Charity and in collaboration with the PCD National Service centres, we are working to develop state-of-the-art diagnostics services for ciliopathies. With the North Thames Regional Genetics Service we have developed a ciliopathy gene panel testing service for mutational analysis that has screened >150 cases. This ‘Ciliome’ diagnostic panel recently received UKGTN clinical accreditation.
  • Understanding how ciliopathy genotype influences the underlying clinical symptoms and disease lifecourse. From these arising genetic advances we are working to develop a better understanding of how genetics influences the clinical outcomes for ciliopathy patients, and this is already leading to advances in prognostic predictions and improved counselling for affected individuals and their families.
  • Gene discovery and functional biology of PCD and Jeune Asphyxiating Thoracic Dystrophy. We are using next-generation sequencing to identify novel causes of ciliopathy diseases in patients that cannot be diagnosed using the current gene panels. In parallel we are investigating the known disease causes to look at the protein networks that regulate the structure and functions of cilia. For PCD we are focused on the dynein arm assembly process using biochemical and proteomic approaches.
  • Novel therapies for PCD and Jeune Asphyxiating Thoracic Dystrophy. We are currently developing in vivo models of PCD and Jeune Asphyxiating Thoracic Dystrophy for novel therapeutics, and with Chris O’Callaghan and Stephen Hart, the group was recently awarded Action Medical Research funding to pursue novel therapies targeted at a particularly prevalent mutational type causing PCD.
  • Retinal and neurological defects underlying juvenile Batten disease. In collaboration with Clare Futter and supported by the Batten Disease Family Association and EU FP7, we are working to understand the basis of retinal and neuronal degeneration in juvenile Batten disease using the Cln3Δex1-6  knockout model.

Grants (last 5 years/current)

Sept 2015 – Aug 2018
British Council Newton-Mosharafa PhD studentship, "Therapeutic potential of dynein assembly defects in Primary Ciliary Dyskinesia", Dr Mahmoud Raafat.
Sept 2014 –Aug 2017 Medical Research Council, “Osteoarthritis may be treated as an environmental ciliopathy”; (co-I for UCL)
May 2015 –May 2019 European Union FP H2020 COST Action, "Translational research in primary ciliary dyskinesia: bench, bedside, and population perspectives (“BEAT-PCD”)"; Basic science work group "Towards Novel Therapies for PCD"
Mar 2015 –Aug 2016 GOSHCC National Call in Translational Paediatric Rare Disease Research, "Next generation sequencing to stratify and personalise the genetic basis of motile cilia disease"
Sept 2015 – Feb 2017 Action Medical Research, “Primary ciliary dyskinesia: tackling the underlying cause of this debilitating, rare condition”
Dec 2013 –Mar 2017 NIHR GOSH UCL Biomedical Research Centre Strategic Award, “The “HIGH-5” Programme - High definition, in-depth phenotyping at GOSH”
Oct 2013 – Sept 2016 Milena Carjaval ProKartagener Foundation, " Genetic and cellular analysis of primary ciliary dyskinesia"

Nov 2012 -Jul 2015

Action Medical Research, “Molecular basis of PCD in a high-prevalence UK Asian population”

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