Mehul Dattani

Section Head

Prof Mehul Dattani

Contact

Genetics & Epigenetics in Health & Disease
Institute of Child Health
30 Guilford Street
London WC1N 1EH

Genetics and Epigenetics in Health and Disease


During the past two decades we have witnessed great technical advances in the analysis of DNA and the completion of the Human Genome Project. These advances have facilitated the discovery of many Mendelian disease-related genes and contributed to a better understanding of the molecular basis of single gene disorders. In fact, such discoveries coupled to careful phenotyping have led to the reclassification of several diseases on molecular grounds.

Gene silencing through DNA methylation involved in genomic imprinting is an example of epigenetic regulation of gene activity. Epigenetic regulation underpins normal development from the fertilised egg to an embryo. It remains to be determined the role of genetic variations and epigenetic regulation in multifactorial disorders such as diabetes, heart disease and cancer. Adult health depends on a complex interaction between inheritance, nutrition and the physical and social environment throughout prenatal development and childhood.

This section focuses on disease gene discovery, the architecture of the genome, inheritance patterns and the regulation of gene expression.

Principal Investigators

Professor Gudrun Moore

Professor Gudrun Moore

Email

Telephone Number:  0207 905 2871

Publications

Background

Gudrun Moore’s scientific career began at York University with a 1st in Biology followed by a SERC funded PhD in muscle development and physiology at the University of Hull. Receiving a three year March of Dimes post-doctoral fellowship, she moved to the Duke University Medical Center, N.C., USA working with Professor Allen Roses on myotonic dystrophy. She returned to the UK in 1985, as an Action Research post-doctoral research fellow in Professor Bob Williamson’s Department of Biochemistry and Molecular Genetics, St Mary’s Hospital Medical School, London. In 1987, her work on X- linked cleft palate in a large Icelandic family provided one of the early successes of genetic linkage analysis. Appointed in 1988 as an Initiative Lecturer in Molecular Biology at the Institute of Obstetrics and Gynaecology at the RPMS, she worked closely with Professor Charles Rodeck building up a Research group that focuses on both fetal medicine and reproduction. She was appointed to a Personal chair in Molecular Biology at Imperial in 2002. In 2006 she moved to UCL-ICH where she led the Clinical and Molecular Genetics Unit until 2014. In 2013 she became the UCL-ICH Deputy Director (Research) and is the Chief Scientific Advisor for the medical charity Sparks

Main Interests/ Achievements

· The role of genetic and epigenetic mechanisms in fetal growth and human reproduction.

There is a continued interest in the concept of "genomic imprinting" and the evidence that different genes or regions of chromosomes are active or inactive depending on their parental origin. From mouse studies it is clear that the early development of the trophoblast is paternally regulated while development of the embryo is under maternal control.

From our research and others, uniparental disomy (UPD) in humans is now well known to be associated with several disease phenotypes, which include growth and reproductive success anomalies. My research group has focussed on fetal growth restriction (FGR) in cases of UPD and those with genomic imprinting effects. One particular model we have extensively studied where the main feature is FGR, is Silver-Russell syndrome (SRS).

We have access to several unique cohort of tissues not including the BBB; a normal pregnancy cohort of trios (mother, father and baby DNA and RNA); fetal tissue with matched maternal DNA; trisomic 13, 18 and 21 tissues with parental DNA; chorion villus samples (CVS) from >1000 pregnancies. All have ethical approval and accompanying detailed anonymous birth outcome data.

Current Research Aims:

1. Analysis of genomic methylation status in syndromes with unusual idiopathic aetiology.

2. Using next generation sequencing to find causal variants in SRS and idiopathic FGR.

3. Studying the importance of imprinted and growth related genes in fetal and embryonic growth in humans, with a view to finding reliable biomarkers for FGR

4. Using next generation technologies to analyse the genetic aetiology of recurrent miscarriage.

· Creation and co-direction of Baby Bio Bank (BBB).

In 2009 Professor Lesley Regan (Imperial College London) and I set up a unique national biobank for complications of pregnancy with 1.8 million donated from WellBeing of Women (WoW). This is called “The London Legacy of Wow Baby Bio Bank (BBB), www.wellbeingofwomen.org.uk/support-us/baby-bio-bank/).

Aims of the BBB:

1. To generate a database of phenotypes and a biological resource, consisting of four major cohorts of complications of pregnancy (plus controls): recurrent miscarriage,FGR, pre-eclampsia and prematurity. Access to this database will be made available to both local and national research groups in order to assess candidate genes and to perform matched RNA expression and protein analysis studies.

2. The resource of biological material will include the collection of whole bloods from “families” (proband, maternal, paternal and grandparents) for DNA extraction and storage of separate serum and plasma samples. In addition, snap frozen placental membranes and placenta will be collected for RNA expression and protein analyses from index as well as future pregnancies. Detailed clinical phenotypes will be recorded.

3. The resource will be used to define genes and proteins that play a biological role in normal pregnancy and to identify DNA sequence variants and alterations in expression in these four complications of pregnancy. In the long-term the results of these studies will have both diagnostic and therapeutic benefits.

Grants (last 5 years/current)
2008 - 2010
Wellbeing of Women, Plasminogen activator inhibator-1, ploycystic ovaries and recurrent miscarriage. (Jointly held with L Regan, Imperial College London) £94,994
2008 - 2012
The Wellcome Trust, "A genome-wide approach to the characterisation of human and murine DNA methylation" (Jointly held with R.Oakey, KCL). £286,000
2009 - 2014
Wellbeing of Women, Baby Bio Bank (Jointly held with Prof Lesley Regan, Imperial College London). £1,8000,000
2011 - 2014
MRC, "The role of methylation in human growth disorders" (Jointly held with R Oakey, KCL). £578,000
2011 - 2014
CHARM, "Finding genetic mutations in rare families with recurrent miscarriage". (Jointly held with L Regan, Imperial College London).  £160,000
2013 - 2016
Medical Research Council, "Investigating the effect of folic acid on the neural tube defect methylome" (PI P Stainer, CO-PI N Greene, A Copp, G moore, R Oakey). £548,826

Professor John Achermann

Professor John Achermann

Email

Telephone Number:  0207 905 2887

Publications

Background

John Achermann is a Wellcome Trust Senior Research Fellow in Clinical Science and Professor of Paediatric Endocrinology at UCL Institute of Child Health. He is an Honorary Consultant at Great Ormond Street Hospital (GOSH), where his work focuses on the multidisciplinary management of children and young people with disorders/differences of sex development (DSD) and adrenal insufficiency. John originally trained in physiological aspects of endocrinology but developed an interest in the molecular genetics of adrenal and gonad development following his work in Larry Jameson’s laboratory in Northwestern University, Chicago (1998-2001). He returned to the UK to establish a research group at UCL Institute of Child Health with support from The Wellcome Trust. John publishes widely on translational aspects of adrenal and reproductive biology and contributes to major textbooks such as Harrison’s Principles of Internal Medicine. He is involved in developing web-based resources and guidance documents, and serves on The Wellcome Trust Expert Review Group for Physiology in Health and Disease. Current team members include Andy Duncan, Federica Buonocore, James Turton and Jenifer Suntharalingham.

Main Interests/Achievements

Our main research interests focus on the molecular genetics of adrenal and gonad development in humans and translational aspects of the management of individuals and families with adrenal insufficiency or disorders/differences in sex development (DSD).

  • The molecular basis of adrenal and gonad development. In collaboration with the Human Developmental Biology Resource, we are exploring the genetic networks and proteins that regulate the adrenal gland and gonads during critical early stages of development.
  • Novel causes of adrenal hypoplasia. We have a long-standing interest in X-linked adrenal hypoplasia congenita (AHC) and DAX-1/NR0B1 and have recently been involved in a project that identified changes in the PCNA-binding domain of CDKN1C as the cause of IMAGe syndrome. We are currently trying to establish the molecular basis of adrenal hypoplasia in those individuals or families where the cause is currently unknown.
  • Investigating gonadal dysgenesis. We have been studying the genetic basis of gonadal dysgenesis through candidate gene approaches and copy number variation, and are using next generation sequencing technologies to try to improve the speed and accuracy of diagnosis in DSD as well as investigating potential novel causes of gonadal dysgenesis.
  • New aspects of steroidogenesis. We have been interested in atypical presentations of conditions affecting steroidogenesis and have described non-classic forms on congenital lipoid adrenal hyperplasia (STAR) and aromatase insufficiency (CYP19). We are currently investigating potential novel regulators of steroidogenesis in the adrenal gland and testicular Leydig cells.
  • Steroidogenic factor-1 in human endocrine systems. We have been studying the contribution of the nuclear receptor steroidogenic factor-1 (SF-1, NR5A1) to endocrine disorders for 15 years and have been involved in studies showing a role for this factor in conditions such as hypospadias, male factor infertility and primary ovarian insufficiency. We are currently studying the role of variants in SF-1 in other population traits, as well as investigating the effect of SF-1 disruption on endocrine function over time. We are establishing a web-based resource of information about SF-1.
  • Approaches to clinical management of DSD and adrenal insufficiency. We are investigating the prevalence of these conditions and reviewing pathways of care, information and experiences for individuals and families.
Grants (last 5 years/current)
Sept 2006 - Aug 2011
Wellcome Trust Senior Research Fellowship in Clinical Sciences, " A combinatorial approach using steroidogenic factor-1 (SF1,NR5A1) to elucidate novel mechanisms in adrenal and reproductive biology". Fellowship/PI.  £1,215,824
Sept 2009 - Feb 2011
CAPES PhD studentship, Bruno Ferraz-de-Souza; (PI) £51,000
May 2008 - Oct 2011
European FP7, "EuroDSD: Investigation into the molecular pathophysiology of Disorders of Sex Development" (Co-investigator; PI for UCL) (Principle Investigator for Work Package: Professor Ken McElreavey, Institute Pasteur, Paris, France; Grant Co-ordinator: Professor Olaf Hiort, University of Lübeck, Germany)
Sept 2011 - May 2012
Wellcome Trust Senior Research Fellowship in Clinical Sciences (extension) "A combinatorial approach using steriodogenic factor-1 (SF1, NR5A1) to elucidate novel mechanisms in adrenal and reproductive biology".  (Fellowship/PI) £193,480
Sept 2012 - Aug 2017
Wellcome Trust Senior Research Fellowship in Clinical Sciences (renewal), "Novel mechanisms in adrenal and reproductive biology". (Fellowship/PI) £1,423,278

Professor Maria Bitner-Glindzicz

Professor Maria Bitner-Glindzicz


Email

Telephone Number:  0207 905 2287

Publications

Background

I am an academic clinician, with a research interest in genetic deafness, both syndromic and non-syndromic. My research ethos is to learn from the families in my clinics and through research, to improve their medical care and genetic services.

I studied medicine at UCL where I did an undergraduate intercalated degree in Human Genetics followed by training in both adult medicine and paediatrics. I am now an Honorary Consultant in Clinical Genetics and Professor of Clinical and Molecular Genetics. I head a research group investigating molecular causes of deafness as well as clinical and epidemiological aspects of hearing loss. I have close links and joint grants with the North East Thames Regional Molecular Genetics Laboratory and am also involved with the European Molecular Genetics Quality Network, which works to ensure quality standards in diagnostic genetic testing.

On appointment in 1999 I established the first and only UK Genetic Deafness clinic, now held at Great Ormond Street Hospital and the Royal National Throat Nose and Ear Hospital, and together with Professor Luxon and Professor Webster, I hold a Dual Sensory Impairment clinic at the National Hospital, Queen Square. This multidisciplinary clinic is a UCL-Partners (Moorfields, Ear Institute, Child Health) cross-Institute collaboration. It has resulted in several large grants and publications describing one of the largest clinical and molecular analyses of Usher syndrome. In my clinics I see both adult and paediatric patients and I offer many the opportunity to participate in research; my research has resulted in the identification of three new genes for deafness, genotype-phenotype studies, publications on genetic epidemiology, and improved genetic services for families.

Main Interests/Achievements

Syndromic and non-syndromic deafness

Since 1992, I have conducted a research programme into genetics of deafness. We have identified genes causing both syndromic and non-syndromic forms of deafness through the detailed study of families presenting to audiology and genetics departments at Great Ormond Street Hospital and recently to UCL-P hospitals. Together with the Nijmegen group, we identified POU3F4, the first gene for non-syndromic deafness in humans, published in Science. The programme continued with discovery of genes for Branchio-oto-renal syndrome, Cardio-Auditory Syndrome and Usher syndrome (deafness and progressive retinal degeneration). Our Regional NHS diagnostic laboratory is now able to offer massive parallel sequencing for a panel of 60 genes causing deafness.

Usher Syndrome

As well as laboratory-based studies we have also engaged in clinical research and genetic epidemiological studies. Our discovery of the USH1C gene in one form of Usher syndrome led to one of the largest clinical and molecular cohort studies worldwide, and improved and initiated diagnostic services for patients in the UK .We have established a specialized clinic for dual sensory impairment, and engaged a hard-to reach group of patients with multisensory impairment in ongoing research. Clinical studies have documented visual acuity and field loss with age, prognostic information which is now used in counselling situations. We have recently established a molecular diagnostic service for patients with Usher syndrome and their families, in our Regional NHS diagnostic laboratory, following a grant from Great Ormond Street Hospital Children’s Charity. I am currently collaborating with Professor Jane Sowden and her group in developing cell models and potential treatments for retinal dystrophy using photoreceptors differentiated from human pluripotent stem cells.

Antibiotic associated deafness

I work on an environmental cause of deafness, antibiotic associated deafness, together with Dr Shamima Rahman. Our observation led of the m.1555A>G mutation in three children with similar histories, to the hypothesis that this might be more common than previously estimated. An application to SPARKS for a small grant, allowed us to screen for the prevalence of this mutation in the ALSPAC cohort of children. We published our findings in 2009 in the New England Journal of Medicine, resulting in interest from the national press. The children’s medical research charity SPARKS awarded us an ‘ Excellence in Medical Research’ award in 2010. This study has led to four further successful grant applications: a UCL Grand Challenges PhD studentship and an overseas PhD studentship; a further small grant from SPARKS and a grant awarded by Action on Hearing Loss. This will enable us to determine the contribution of this form of preventable deafness to hearing loss in babies from Neonatal Intensive Care Units, since approximately 40,000 babies per year in England are treated with aminoglycosides. This work has also has catalyzed links with industry for the development of bedside genetic testing.

Grants (last 5 years/current)
2013 - 2015
Great Ormond Street Hospital Biomedical Research Centre, Towards bedside genetic testing to prevent aminoglycosis-induced hearing loss. PI, Maria Bitner-Glindzicz, Co-Is, Dr Shamima Rahman, Prof Neil Marlow. £49,000
2013 - 2014
Great Ormond Street Hospital Biomedical Research Centre, Developing cell models and treatment for retinal dystrophy using photoreceptors differentiated from human pluripotent stem cells.  PI, Jane Sowden, Co-I, Maria Bitner-Glindzicz.  £49,000
2012 - 2013
Technology Strategy Board (Stratified Medicine), Valuing a test for the m.1555A>G mitochondrial RNA mutation to prevent deafness in neonates caused by aminoglycoside antibiotic therapy.  PI, Paul Weinberger (Diasolve); Co-Is, Maria Bitner-Glindzicz, Martin Lee, Mark Laverick (Flourogenics).  £99,000
2012 - 2015
Special Trustees of Great Ormond Street Hospital, Diagnostic testing for Usher syndrome using next generation sequencing.  PI, Maria Bitner-Glindzicz; Co-Is, Dr Nick Lench, Prof Tony Moore, Dr Kaukab Rajput.  £303,000
2011 - 2014
Special Trustees of Great Ormond Street Hospital Leadership Award, Genetics of Childhood Deafness. PI, Maria Bitner-Glindzicz.  £403,694
2011 - 2014
Sparks & UCL Grand Challenges PhD studentship, Mitochondrial function in patients and m.1555A>G mitochondrial mutation.  PI Maria Bitner-Glindzicz & Dr Shamima Rahman.  £75,000
  RNID (now Action on Hearing Loss) Summer studentship, "Molecular basis of X-linked deafness - translation from research to service" for Miss Janice Lee. Co-PI, Dr Nick Lench
2010 - 2013
RNID, DNA diagnostics for deafness using next generation DNA sequencing.  PI, Prof Guy van Camp; Co-PI, Prof Paul Coucke, Maria Bitner-Glindzicz.  £147,250
2009 - 2012
UCL Combined Biomedical Research Centre Collaborative Research Grant, The clinical and molecular investigation of Usher syndrome in preparation for a clinical treatment for Usher-related blindness.  PI, Maria Bitner-Glindzicz & Mr Andrew Webster (UCL IOO); Co-Is, Prof Robin Ali; Prof Linda Luxon.  £397,000
2006 - 2011
Medical Research Council, Collaborative Centre of Epidemiology for Child Health.  PI, Prof Carol Dezateux; Co-Is, Dr Helen Bedford, Dr Maria Bitner-Glindzicz, Prof Timothy Cole, Dr Mario Cortina-Borja, Dr Ruth Gilbert, Prof Harvey Goldstein, Prof David Ingram, Dr Catherine Law, Prof Marie-Louise Newell, Prof Catherine Peckham, Prof Christine Power, Dr Jugnoo Rahi, Dr Pat Tookey, Dr Angela Wade, Dr Ian Wong. £1,500,000
2009 - 2011
SPARKS Research Training Fellowship to Dr Lily Islam, Investigating genetic causes of congenital eye defects to support clinical diagnosis and management.  PI, Dr Jane Sowden; Co-Is, Maria Bitner-Glindzicz, Dr Ken Nischal.  £156,000
2009 - 2011
Birth Defects Foundation, Investigation of the genetic basis of congenital hypopituitarism in a cohort of patients with complex developmental disorders.  PI, Prof Mehul Dattani; Co-Is, Maria Bitner-Glindzicz, Dr JP Martinez.  £120,000
2008 - 2009
GOSH/ICH Biomedical Research Centre, One Year Clinical Training Fellowship to Dr Lily Islam, The Genetics of Eye Developmental Disorders.  PI, Dr Jane Sowden; Co-Is, Maria Bitner-Glindzicz, Dr Ken Nischal.  £65,000
2011
Deafness Research UK, Identifying genes causing deafness in the British Bangladeshi population.  PI, Maria Bitner-Glindzicz; Co-I, Dr Nick Lench.  £30,000
2011 - 2014
International Islamic Bank, Ototoxicity in the deaf population of Sierra Leone.  Primary Supervisor, Prof Shakeel Saeed (Ear Institute); Secondary Supervisor, Maria Bitner-Glindzicz.  £75,000

Professor Mehul Dattani

Professor Mehul Dattani

Email
Telephone Number:  0207 905 2657

Publications

Background

Professor Mehul Dattani is Professor of Paediatric Endocrinology based at the UCL Institute of Child Health, and Head of Paediatric Endocrinology at Great Ormond Street Hospital for Children (GOSH), UCLH and ICH, and has an active clinical practice encompassing all areas of paediatric and adolescent Endocrinology at GOSH and University College London Hospitals (UCLH). He is Chair of the Programme Organizing Committee of the European Society for Paediatric Endocrinology (ESPE), and was previously (2010-2013) the Chair of the British Society for Paediatric Endocrinology and Diabetes. He is Section Head of Genetics and Epigenetics in Health and Disease within GGM. He leads an active research group investigating the molecular basis of congenital hypopituitarism and other rare endocrine disorders. Professor Dattani also leads a busy clinical service in Endocrinology, and looks after children with a range of endocrine disorders including congenital hypopituitarism, SOD, IGHD, disorders of adrenal development, disorders of sex development, thyroid disorders, disorders of puberty, and rare endocrine disorders such as insulin resistance. His clinical practice is based at Great Ormond Street Hospital for Children and at University College London Hospitals. He also delivers an outreach service at Canterbury Hospital, Whittington Hospital, West Middlesex Hospital, Mater Dei Hospital, Malta, and Dubai Hospital, UAE.

Main Interests/Achievements

The research programme focuses on the following conditions:

a) Congenital hypopituitarism/Septo-optic dysplasia.

Professor Dattani looks after a large cohort of these patients (approximately 150 patients with SOD and 100 patients with CPHD). The studies focus on understanding the pathogenesis and optimizing the management of these conditions. A number of genetic causes have been identified, many by our group, accounting for approximately 10-20% of cases. The rest remain unexplained, and we are now focusing on the use of novel genetic/genomic techniques to identify genetic mutations underlying the rest of the cases. These include whole exome sequencing and homozygosity mapping. Additionally, clinical studies are focusing on the clinical phenotypes, including endocrine, neurocognitive and weight dysregulation. The studies have led to the accumulation of more than 2000 DNA samples from national and international paediatric endocrine and genetic centres.

b) Brain tumours

The recent discovery that adamantinomatous craniopharyngiomas (ACP) are associated with activating mutations in the gene encoding beta-catenin (CTNNB1) led to the generation of a murine model of ACP, using conditional transgenesis in collaboration with the group of Dr. Juan Pedro Martinez-Barbera in the Birth Defects Centre at ICH.  This model will inform the development of novel therapies for use in humans to treat this devastating tumour. Further research will also focus on understanding the pathogenesis of hypothalamic hamartomata, benign tumours associated with gelastic seizures, neurodevelopmental delay and precocious puberty.

c) Hypogonadotropic hypogonadism

Considerable research has focused on understanding the pathogenesis of these disorders. These include both Kallmann syndrome and normosmic hypogonadotropic hypogonadism. We have recently reported an overlap between Kallmann syndrome and hypopituitarism. Given that genetic mutations have been identified in only 20% of patients with these disorders, we aim to establish the molecular basis of these conditions in our patient cohort, analyzing DNA samples for mutations in known genes and then looking for mutations in novel candidate genes. In the future, we hope to collaborate with other centres in an attempt to optimize the treatment of these individuals, namely investigating the use of hCG and recombinant FSH compared with standard existing testosterone treatment.

d) Effects of GH on neurocognition and brain structure

We have recently shown the presence of specific neurocognitive deficits and alterations in brain structures such as the hippocampus, cortico-spinal tracts and corpus callosum as assessed by volumetric MRI and diffusion tensor imaging in patients with GH deficiency as compared with patients with short stature. We now hope to look at the effect of GH treatment on these abnormalities.

e)  The molecular basis of other rare endocrine disorders

Recent collaborations with other clinical scientists have led to the identification of the molecular basis of other disorders such as Thyroid Hormone Resistance and other unusual thyroid hormone deficiencies as well as obesity syndromes such as those due to SIM1 deficiency.  The clinical practice at GOSH with it enrichment for rare disorders facilitates such collaborative studies.

2013 - 2014 GOSH Children's Charity Clinical Research Starter Grant.  Quantification of oxytocin and arginine-vasopressin in patients with complex hypothalamo-pituitary disorders including septo-optic dysplasia £49,734. PI
2012 - 2015 Children with Cancer UK Charity/GOSH Children's Charity, £79,152. Co-Investigator
2012 - 2015 GOSH Children's Charity, Research Leader Award: Investigations of Disorder of forebrain, eye and pituitary development £130,702
2011 - 2013 Novo Nordisk, Norident International Outcomes Study, £73,092
2011 - 2012 Pfizer, KIGS International Outcomes Study £73,092
2011 - 2014 MRC Australia, Functional analysis of a novel genetic mouse model for congenital growth hormone deficiency Australian $501,299.00, Co-Investigator
2010 - 2011 GOSH Children's Charity, Investigations of Disorder of forebrain, eye and pituitary development. £129,314
2010 - 2011 Biomedical Research Centre GOSH/ICH, Genotype-Phenotype correlations in Craniopharyngioma, £3000
2009 - 2012 BSPED Merck-Serono award, Investigation of the role Kallmann genes in the aetiology of hypopituitarism, £25,000
2009 - 2011 Birth Defects Foundation, Investigation of the genetic basis of congenital hypopituitarism in a cohort of patients with complex developmental disorders, £120,000
2009 - 2012 Wellcome Trust, The role of Sox2/SOX2 in hypothalamo-pituitary development, £359,039

Professor Peter Hammond

Professor Peter Hammond
Email
Telephone Number: 0207 905 2399
Publications

Background

I originally trained in mathematics and computer science at Oxford University and Imperial College.  Previously, I worked in pure mathematics, artificial intelligence and for the past ten years I have focused on computational biology with applications in craniofacial dysmorphism and cell-ECM interactions related to scarring in heart tissue following myocardial infarction.

I am particularly interested in multi-disciplinary research that develops mathematical and computational techniques and applies them to biomedical problems.  Currently, 50 or so neuro-cognitive disorders are being studied in association with clinical geneticists, molecular biologists and neurocognitive scientists in Argentina, Australia, Belgium, Brazil, canada, Chile, China, Finland, Ireland, Italy, Norway, The Netherlands, UK and USA.

Main Interests/Achievements

For the past fourteen years, my lab has pioneered methods for computational analysis of abnormal craniofacial growth and development in humans and in animal models.  In that time, it has become a world leader in the analysis of facial dysmorphism in rare genetic syndromes.  At nearly 10,000 images covering healthy controls and over 50 rare conditions, it also has by far the largest collections of 3D facial scans of individuals affected by genetic syndromes.  Most of these images have been collected through extensive travel to visit collaborators and recruit affected families, much of it overseas.  Our research is paradigm shifting in its introduction of objective, computational methods to the analysis of facial dysmorphology that previously relied on manual measurement, conventional 2D photometry and subjective description.  It has made a number of significant achievements.

2000/04 Pioneered and developed computational modeling of facial dysmorphism
2005 Demonstrated accurate automated recognition of facial dysmorphism a range of genetic condtions and for particular regions of the face
2005 Contributed to the identification of a role for the gene GTF2IRD1 in facial development in a multi-disciplinary cognitive, facial and molecular analysis of the condition Williams syndrome and a related mouse model
2008 Identified discriminating and significant facial asymmetry, for the first time, in children with autism and in unaffected mothers of children with autism; and, demonstrated a potential link with known brain asymmetry in children with autism
2008 Contributed to a multi-species craniofacial analysis involving humans with Bardet-Biedl syndrome, knock-out mice and zebra fish models that demonstrated inhibition of neural crest cell migration causing associated facial dysmorphology and Hirschprungs disease
2011
Developed and demonstrated utility of face signature and face signature graphs in study of rare conditions as well as large-scale phenotyping
2013
Delineated a link between facial dysmorphism and cognitive impairment in children with confirmed prenatal alcohol exposure but who are difficult to diagnose clinically
2013
Demonstrated the link between gene dosage sensitivity and opposing effects on facial development in several genomic regions

Grants (last 5 years/current)

Period 2012 -2017
Title Craniofacial and CNS Pathology in a Mouse FASD Model
Amount US$1,194k
Funding NIAAA/NIH (through CIFASD consortium)
PI Dr Kathy Sulik,l North Carolina University, USA
Sub-contract US$161k Prof Peter Hammond, Molecular Medicine Unit, ICH, UCL
Period           
2012 - 2017
Title Craniofacial analysis in fetal alcohol syndrome
Amount US$1,781k
Funding NIAAA/NIH (through CIASD consortium)
PI US$571k Prof Peter Hammond, Molecular Medicine Unit, ICH, UCL
Co-PI Prof Tatiana Foroud, Indiana University, USA
Period            
2009 - 2010
Title An investigation into the facial phenotype of Pradar Willi syndrome (PWS) and its association with genetic sub-type, gender, and growth hormone deficiency
Amount £50k
Funding Bailey Thomas Charitable Fund (UK)
PI Prof Peter Hammond, Molecular Medicine Unit, ICH, UCL
Collaborator Prof Tony Holland, Dept of Psychiatry, University of Cambridge

Doctor Khalid Hussain

Doctor Khalid Hussain

Email

Telephone Number: 0207 905 2128

Publications

Background

Abnormalities in glucose homeostasis (hypo and hyperglycaemia) are common in the childhood period. Hypoglycaemia can be due to many different causes. A delay in the diagnosis and inappropriate management of hypoglycaemia can lead to brain damage and associated complications such as mental retardation, epilepsy and cerebral palsy. The most severe forms of hypoglycaemia are due to congenital hyperinsulinism (unregulated insulin secretion). On the other hand hyperglycaemia is commonly observed in children with different types of diabetes mellitus. Great Ormond Street Children’s Hospital NHS Trust (GOSH) is a national and international referrals centre for patients with severe forms of hypoglycaemia especially those with congenital hyperinsulinism. The congenital hyperinsulinism centre at GOSH is designated by NHS England as a centre of excellence for the diagnosis and management of patients with hyperinsulinism. Patients with rare and complex (syndromic) types of diabetes mellitus are also referred to Dr. Hussain from around the world.

Main Interests/Achievements

My research group focuses on four main areas related to glucose physiology:

1. Hyperinsulinaemic Hypoglycaemia (HH): Understanding molecular mechanisms and developing novel therapeutic strategies. The genetic basis of HH is currently only known in about 50% of patients. A major part of our research has focused on understanding the genetic mechanisms that lead to HH. As part of a Wellcome Trust and MRC project grants (in collaboration with Professor Sian Ellard from Exeter), we have recruited a large cohort of patients with HH (more than 1500 DNA samples collected so far) who have been systemically phenotyped and genotyped. We are now using a combination of candidate gene approach, homozygosity mapping, next generation exome and whole gene sequencing strategies to identify the genetic aetiology of HH in these patient groups.

In collaboration with Professor Timo Otonkoski from Finland we have described a novel imaging technique (18F-DOPA-PET/CT scanning) of the pancreas in patients with HH which has completely revolutionized the management of these complex patients. More recently in collaboration with Dr. Robert Semple from Cambridge University Institute of Metabolic Studies we described the first patients with an unusual form of hypoketotic hypoglycaemia due to an activating mutation in the AKT2 gene. AKT2 plays a key role in the regulation of downstream insulin signaling pathway.

We are also about to describe a completely new treatment modality for patients with the most severe forms of diffuse HH using MTOR inhibitors, thus avoiding the need for a radical pancreatectomy.

2. Unraveling the molecular basis of pancreatic development and of complex (syndromic) forms of diabetes: In collaboration with colleagues from around the world and Professors Andrew Hattersley and Sian Ellard from Exeter we are also interested in understanding the molecular and genetic basis of pancreatic development and complex (syndromic) forms of diabetes mellitus. These collaborations have provided fundamental novel insights into pancreatic development and the molecular basis of syndromic forms of diabetes mellitus.

3. Understanding how hypoglycaemia leads to brain injury: A key component of our research focuses on trying to understand how hypoglycaemia leads to brain injury. As part of a Great Ormond Street Hospital Programme grant (in collaboration with Professors Faraneh Vargha-Khadem and David Gadian from the ICH) we have been undertaking comprehensive and thorough studies which examine continuous brain electrical activity in relation to concurrent changes in blood glucose levels, counter-regulatory hormones and intermediary metabolites (such as fatty acids and ketone bodies). The anatomical changes in the brain due to hypoglycaemic brain injury are carefully defined by using MRI.

4. Understanding how mutations in the SLC29A3 gene lead to a novel syndrome (pigmented hypertrichosis and insulin dependent diabetes mellitus, PHID syndrome). We described a novel autosomal recessive syndrome characterised by pigmentary hypertrichosis and autoantibody negative insulin dependent diabetes mellitus (PHID syndrome) associated with pancreatic exocrine insufficiency. Using autozygosity mapping in five families with PHID syndrome we established that mutations in SLC29A3, which encodes for the protein human equilibrative nucleoside transporter 3 (hENT3), cause PHID syndrome. Mutations in SLC29A3 have also been linked to H syndrome and familial Rosai Dorfman Disease (RDD) and sinus histiocytosis with massive lymphadenopathy (SHML). Thus SLC29A3 mutations result in a spectrum of human genetic disorders with a variable phenotype. A hallmark of PHID and H syndromes is the chronic inflammation characterised by the persistently raised erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP).

Grants (last 5 years/current)

The Wellcome Trust Project Grant: “Fasting and protein sensitive Hyperinsulinaemic Hypoglycaemia due to HADH mutations: Understanding novel mechanisms of fatty acid and amino acid induced insulin secretion”. Amount awarded £184,000 June 2009 for three years (PI Dr. Khalid Hussain co-applicants Dr. Simon Eaton, Dr. Kevin Mills and Dr. Shanta Persaud).

The Children’s Hyperinsulinism Fund. Project: “The genetics of hypoglycaemia.” Amount awarded £50,000: March 2009 for 1 year (PI Dr. Khalid Hussain).

Biomedical Research Centre funding (via the National Institute of Health Research): Project: “The role of the nucleoside transporter gene SLC29A3 in pancreatic endocrine and exocrine tissue.” Amount awarded £96,911: February 2009 for 2 years (PI Dr. Khalid Hussain, co-applicants Dr. Simon Eaton and Professor Raoul Hennekam).

Diabetes UK Project grant: “Understanding the genetic basis of pancreatic agenesis.” Amount awarded £120,000: August 2008 for 2 years (PI Dr. Phil Marsh, co-applicants Professor Peter Jones and Dr. Khalid Hussain).

Great Ormond Street Hospital for Children NHS Trust programme grant. Project: “Hypoglycaemia and brain injury” Amount awarded £675,882: April 2008 for 3 years (PI Dr. Khalid Hussain, co-applicants Professor David Gadian, Dr. Mathew Pitt and Professor Faraneh Vargha-Khadem).

The Wellcome Trust Project grant: “Defining genotype/phenotype relationships in known and novel causes of Hyperinsulinaemic Hypoglycaemia.” Amount awarded £272,000: December 2006 for 3 years (PI Dr. Khalid Hussain, co-applicants, Dr. Julian Shields and Professor Sian Ellard).

European Framework 7 Programme. HEALTH.2013.1.2-1: Development of imaging technologies for therapeutic interventions in rare diseases. FP7-HEALTH-2013-INNOVATION-1 SME-targeted Collaborative Project. Project title “Personalized diagnosis and treatment of hyperinsulinemic hypoglycaemia caused by beta-cell pathology.” Amount awarded 6,000,000 Euros (Co-ordinator Martin Gotthardt, co-applicants Dr. Khalid Hussain, Dr. Douwe Dijk, Dr. Gooitzen van Dam, Dr. Martin Béhé, Dr. Winfried Brenner, Dr. Damian Wild, Dr. Timo Otonkoski, Dr. Pirjo Nuutila, Dr. François Pattou, Dr. Theo Lasser, and Dr. Christian Velez)

The NIHR Rare Diseases Translational Research Collaboration award. Project title: “Congenital Hyperinsulinism (CHI); Unravelling the Phenotypic Diversity in CHI”. Amount awarded £100,000 September 2013 (PI Professor Mark Dunne, co-applicants Dr. Khalid Hussain, Dr. Indi Banerjee, Dr. Mohammed Didi, Professor Sian Ellard, Dr. Gary Cooper)

Ipsen Pharmaceutical Company. Project title: “Lanreotide therapy for patients with Congenital Hyperinsulinism (CHI)”. Amount awarded £5000 September 2013 (PI Dr. Khalid Hussain)

Clinical Research Starter Grant: Great Ormond Street Hospital Children’s Charity. Project title: “Identifying the molecular basis of polycystic kidneys associated with Hyperinsulinaemic Hypoglycaemia.” Amount awarded £95,000 February 2013 (PI Dr. Detlef Bockenhauer, co-applicant Dr. Khalid Hussain)

European Society for Paediatric Endocrinology Research (ESPE) Unit award. Project title “understanding the genetic basis of syndromic forms of diabetes mellitus”. Amount awarded £75,000 October 2012 (PI Dr. Khalid Hussain, co-applicants Dr. Klemens Raile and Professor Feyza Darendelier).

Medical Research Council (MRC) project grant. Project title: “Defining novel genetic mechanisms of Congenital Hyperinsulinism.” Amount awarded £770,000 March 2011 (PI Dr. Khalid Hussain, co-applicant Professor Sian Ellard).

Biomedical Research Centre funding (via the National Institute of Health Research). Project: “Defining genotype/phenotype relationships in known and novel causes of Hyperinsulinaemic Hypoglycaemia.” Amount awarded £6000, September 2009 for 2 years (PI Dr. Khalid Hussain co-applicant Dr. Ritika Kapoor).

Higher Education Funding Council for England (HEFCE) Clinical Senior Lectureship award. Awarded £250,000 for 5 years starting August 2009

Doctor Philip Stanier

Doctor Philip Stanier

Email

Telephone Number:  0207 905 2867

Publications

Background

Dr Philip Stanier is Reader in Craniofacial Developmental Biology and Genetics. Prior to joining UCL-Institute of Child Health in 2006, he previously worked at Imperial College London, Queen Charlotte’s and Chelsea Hospital following award of a PhD at St Mary’s Hospital London in 1990. Research efforts focus on elucidation of the genetic and developmental basis for birth defects, particularly cleft lip and palate, neural tube defects, fetal growth disorders and several rare diseases.

Main interests/Achievements

Cleft lip and/or palate (CL/P): Identification of the gene for X-linked cleft palate (TBX22) in 2001 and since, establishment of its prevalence as a common genetic cause, not only of cleft palate, but also of submucous cleft palate, occasionally cleft lip, ankyloglossia, hypodontia and the CHARGE-like Abbruzzo-Erickson syndrome. Currently investigations include the development of palatal muscles in human cleft palate and Tbx22 knockout mice with a view to developing improved treatment, particularly for submucous cleft palate, which remains a challenge for surgical intervention. We have collected >600 samples from patients which underpins further gene identification projects and ongoing studies include the application of a variety of sequencing and cytogenetic methodologies towards revealing the underlying molecular pathology of nonsyndromic CLP.

Neural tube defects (NTD): Identification of the crucial role for the planar cell polarity pathway in early neural tube development was achieved by identifying mutations in Vangl2, Celsr1 and Scrib in a series of mouse models with craniorachischisis. More recently we demonstrated that mutations in these genes are involved in human NTDs. Recent and ongoing projects have identified mutations in a number of other mouse and human genes, and implicated the mitochondrial glycine cleavage system as a potentially important branch of the folate pathway in terms of NTD occurrence. We are also investigating folate related methylation in NTD susceptible mice, to identify locus specific epigenetic modifiers of NTD.

Genomic imprinting, fetal growth restriction and complications of pregnancy: Recent highlights have been identifying the contribution of genes such as PHLDA2 and IGF2 to birth weight in different stages of pregnancy.

Rare diseases: Identification of the molecular basis for the rare intellectual disability condition Lenz-Majewski syndrome, characterized by sclerosing bone dysplasia, provides an ongoing project to better understand the link between phosphatidylserine production and bone metabolism. Other intellectual disability syndromes associated with cerebellar hypotrophy are currently under investigation.

Grants (last 5 years/current)
2014 - 2017
UCL-GOSHCC Impact studentship, The role of FGF signalling in the pathogenesis of craniofacial birth defects.  CO-I (E.Pauws, P Stanier).  £77,700
2013 - 2016
Medical Research Council, "Investigating the effect of folic acid on the neural tube defect methylome".  PI (P Stanier, N Greene, A Copp, G Moore, R Oakey).  £548,826
2012 - 2014
CLEFT, "Discovery of novel causative genes in familial cleft lip and palate".  PI (P Stanier, M Lees, P Beales, GE Moore).  £128,388
20112 - 2014
GOSHCC, "Genetic basis of inherited birth defects".  PI (P Stanier).  £250,817
2010 - 2012
BRC, "Investigating the genetic basis of neural tube defects".  Co-I (N Greene, P Stanier, D Thompson, A Copp)  £99,844
2009 - 2012
Medical Research Council (G20522), Planar cell polarity signalling and mammalian neurulation.  Co-I (AJ Copp, NDE Greene and P Stanier).  FEC £1,043,457
2008 - Mar 2011
Sparks, Role of SUMO pathway genes in CLP, PI (P Stanier and M Lees).  £143,425

Doctor Sara Mole

Doctor Sara Mole

Email

Telephone Number:  0207 679 7257

Publications

Background

I read Natural Sciences at the University of Cambridge, and undertook my PhD at Imperial College, in Biochemistry. Two postdoctoral positions followed, one continuing my PhD cancer research under David Lane at Imperial Cancer Research Fund, and the second under Bruce Ponder at the University of Cambridge in which I followed my developing interest in molecular genetics of human disease. I came to UCL in 1992, when I was appointed a Lecturer in Molecular Genetics in the Department of Paediatrics. I am currently a Reader in Molecular Cell Biology at the UCL Institute of Child Health, with my laboratory in the MRC Laboratory for Molecular Cell Biology on the Gower Street campus of UCL.

Main Interests/Achievements

I am interested in disease caused by genetic changes and how study of these mutations and their effects can reveal important and complex aspects of cell biology that may otherwise be beyond current appreciation. My main research interest is the molecular genetics and biology of the neuronal ceroid lipofuscinoses (NCL) or Batten disease, a group of inherited neurodegenerative diseases mainly affecting children that affect lysosome homeostasis. This group of diseases are rare but understanding their biology may open new avenues for understanding and treating more common neurodegenerative conditions. Thirteen genes have now been identified, and I continue to work towards identifying the remainder, making use of next generation DNA sequencing technology. I curate the NCL Resource web site, which acts as a gateway for Batten disease and includes the Mutation Database which I maintain on behalf of the international NCL community (http://www.ucl.ac.uk/ncl).

I have a particular interest in the biology of CLN3 and CLN10, highly conserved genes, and of CLN2, CLN6 and CLN8, vertebrate genes. Within my own laboratory we use mammalian systems and the ‘micromammal’ yeast model organism Schizosaccharomyces pombe. The function of CLN3 is complex and more important than was expected, and the fission yeast model system has recently revealed novel aspects of its function. Significantly we discovered that an intragenic deletion of CLN3 shared by most patients with juvenile NCL does not completely abolish CLN3 function, which has important implications for future therapy development. We use both systems and hypothesis driven approaches in yeast models for these and other diseases to identify genetic interactors that provide new therapeutic targets and to screen for new drugs that could be developed for treatment. We are also exploring the potential of a gene therapy that targets the visual loss in NCL since this would significantly improve the quality of life of affected children, and will complement any brain-targeted therapies.

Within UCL, I lead on Athena SWAN in my department (silver status since 2009), equality and diversity in the Faculty of Life Sciences, Rare Diseases in the School of Life and Medical Sciences, and have responsibility for patient and public involvement, and public engagement on UCL NIHR Biomedical Research Centre Strategic Board. I received the Provost’s Public Engagement Award (Senior Staff) in 2013. Outside UCL, I work closely with the Batten Disease Family Association, acting as Scientific Advisor, and with the Equality Challenge Unit on the Athena SWAN award scheme.

Grants(last 5 years/current)
2011 - 2014
EU FP7-HEALTH-2011-single-stage CP-FP.  No. 281234.  A Treatment-Orientated Research Project of NCL Disorders as a Major Cause of Dementia in Childhood (DEM-CHILD). €2,998,795; €401,347 to UCL for specified projects
  Three current UCL IMPACT Awards, in conjunction with the Batten Disease Family Association (£114,428) and the German NCL Foundation (£98,000)
  Additional funding from the USA Batten Disease Support and Research Association and the Children's Brain Disease Foundation

Doctor Shamima Rahman

Doctor Shamima Rahman

Email

Telephone Number:  0207 905 2608

Publications

Background

Dr Shamima Rahman is a Reader in Paediatric Metabolic Medicine at the UCL Institute of Child Health, and an Honorary Consultant in the Metabolic Department at Great Ormond Street Hospital where she runs a specialised mitochondrial disease clinic. Dr Rahman trained in Medicine at Oxford University, and in Paediatrics at the Royal Hospital for Sick Children, Bristol; Great Ormond Street Hospital, London; and the Oxford Radcliffe Hospitals. She established the Mitochondrial Research Group at ICH during a clinical lectureship in 2000, following a research fellowship at the Royal Children’s Hospital, Melbourne, Australia (1993-1994) and a subsequent PhD in molecular medicine at UCL (1996-1999).

Dr Rahman is also an Editor of the Journal of Inherited Metabolic Disease (the highest impact journal in her field), a member of the Education and Training Advisory Committee of the Society for the Study of Inborn Errors of Metabolism since 2008 (in which capacity she has been part of the Faculty of the annual SSIEM Academy which trains physicians and biochemists from around the world in metabolic medicine), and chair of the Athena SWAN team at ICH.

Main Interests/Achievements

The Mitochondrial Research Group at ICH aims to identify the genetic basis of and novel treatments for mitochondrial diseases presenting in childhood. These are devastating often multisystemic diseases that, because of the fundamental requirement of mitochondria for energy generation in almost all human cells, can present with any symptom or combination of symptoms affecting any tissue or organ system. Over the last 14 years since the group was established, we have used a combined genomic approach encompassing homozygosity mapping, candidate gene analysis, whole exome sequencing and functional characterisation, to identify defects in more than 30 different genes in our patients. This work has revealed heterogeneous disease mechanisms, and we are currently trying to understand the tissue specificity of some of these gene defects, as well as evaluating novel therapies in cell culture models.

Current Research Themes:

1. Elucidation of the molecular basis of human mitochondrial disease.

We have identified a number of novel nuclear disease-causing genes using an integrative genomics approach including homozygosity mapping, candidate gene analysis, targeted gene panel and whole exome next generation sequencing and functional cell complementation studies. Genes identified include subunits of and assembly factors for individual respiratory chain enzyme complexes, genes needed for maintenance and expression of the mitochondrial genome, and a gene involved in the biosynthesis of coenzyme Q10. We are now part of the pilot Genomics England study, which aims to identify further disease genes by whole genome sequencing of trios. Ongoing work will include deep phenotyping of patient samples to understand the molecular basis underpinning the enormous clinical and biochemical heterogeneity of childhood-onset mitochondrial diseases.

2. Search for curative treatments and strategies to prevent mitochondrial disease.

We are investigating candidate small molecules, including coenzyme Q10, folate, ketones and fatty acids, as biomarkers and potential therapeutic targets in mitochondrial disease.

3. The MRC Centre for Translational Research in Neuromuscular Disease Mitochondrial Disease Patient Cohort (UK)

We are also conducting a large natural history study of mitochondrial diseases, in collaboration with Newcastle and Oxford Universities. So far more than 1000 patients have been recruited into this study, making it the largest natural history study of mitochondrial disease in the world.

4. Mitochondrial dysfunction and common disease

In collaboration with Prof Maria Bitner-Glindzicz, we are performing a penetrance study of a mitochondrial DNA mutation that predisposes to exquisite aminoglycoside ototoxicity, to determine whether screening for this mutation prior to aminoglycoside administration can prevent deafness in susceptible individuals. We are also exploring the cost-effectiveness of bedside genetic testing strategies to prevent this form of deafness.

Ongoing collaborations have examined the contribution of mutations affecting mitochondrial enzymes including fumarate hydratase to the development of cancers and, with Dr Gyorgyi Szabadkai at UCL, to resistance to chemotherapeutic reagents such as cisplatin.

Current members of the Mitochondrial Research Group at ICH

Postdoctoral research associates

Dr Elisa Fassone

Dr Rojeen Shahni

Clinical research fellow

Dr Yehani Wedatilake

PhD students

Marta Kanabus

Mary O'Sullivan

Research nurse

Latifa Chentouf

Grants (Last 5 years & current)
2014 - 2015

Lily Foundation, Research nurse

PI, Shamima Rahman. £45,113

2013 - 2015

Great Ormond Street Hospital Biomedical Research Centre, Project grant

Towards bedside genetic testing to prevent aminoglycoside-induced hearing loss. PI, Maria Bitner-Glindzicz; Co-Is, Shamima Rahman, Neil Marlow. £49,000

2013 - 2014

Lily Foundation, Project grant

Whole Exome Sequencing to diagnose mitochondrial disorders without muscle respiratory chain deficiency. PI, Shamima Rahman. £20,000

2012 - 2015

Great Ormond Street Hospital Children’s Charity, Research Leadership award

Inborn errors of metabolism (genetic metabolic diseases). PI, Shamima Rahman. £177,946

2012 - 2015

Wellcome Trust, Research Training Fellowship for Dr Yehani Wedatilake.

The molecular basis of cytochrome c oxidase deficiency. Sponsor, Shamima Rahman; secondary supervisor, Jan-Willem Taanman. £232,545

2011 - 2014

Muscular Dystrophy Campaign, Project grant, 3 years

Identification of nuclear gene defects underlying multiple mitochondrial respiratory chain defects using exomic sequencing. PI, Shamima Rahman; Co-I, Elia Stupka. £149,989

2011 - 2013

Great Ormond Street Hospital Children’s Charity, Neuroscience project grant

Biogenesis of mitochondrial respiratory chain complex I: relevance to paediatric neurological disease and pathology. PI, Shamima Rahman; Co-Is, Jan-Willem Taanman, Elia Stupka. £271,064

2011 - 2014

Vitaflo, PhD studentship

Development of a cell-based system to investigate which mitochondrial respiratory chain defects may respond to a ketogenic diet. PI, Shamima Rahman; Co-I, Simon Heales. £109,252

2011 - 2014

UCL Grand Challenges and Sparks, PhD studentship for Mary O’Sullivan.

Mitochondrial function in patients with m.1555A>G mitochondrial mutation. Co-Primary supervisors Shamima Rahman and Maria Bitner-Glindzicz, £70,000

2011 - 2012

Climb, Project grant

Development of a COX gene panel: High throughput sequence analysis of candidate genes implicated in cytochrome c oxidase deficiency using a targeted re-sequencing approach. PI, Shamima Rahman, Co-I, Nick Lench. £14,500

2010 - 2013
Child Health Research Appeal Trust, PhD studentship Elucidation of the molecular mechanisms responsible for the central folate deficiency associated with mitochondrial disease. PI, Simon Heales; Co-I, Shamima Rahman. £70,000
2010 - 2011

Children’s Liver Disease Foundation, Small project grant

Investigation of the genetic basis of mitochondrial liver disease. PI, Shamima Rahman. £5,000

2010 - 2013

RNID (now Action on Hearing Loss), Project grant

The contribution of m.1555A>G to deafness in very preterm children [following neonatal intensive care]. PIs Maria Bitner-Glindzicz and Shamima Rahman; Co-Is,

£157 659

2009 - 2012
Ataxia UK, Project grant, 3 years Coenzyme Q10 a potential therapeutic target for ataxia: Evaluation of therapeutic strategies. PI, Iain Hargreaves; Co-Is Shamima Rahman, Simon Heales. £70 350
2009 - 2012

Medical Research Council, cohort grant, 3 years

The MRC Centre for Translational Research in Neuromuscular Disease Mitochondrial Disease Patient Cohort (UK). PI, Doug Turnbull; Co-Is, Shamima Rahman, Patrick Chinnery, Robert Taylor, Michael Hanna, Joanna Poulton, Robert McFarland. £731,996

2008 - 2009

Sparks Children’s Charity, Project grant, 1 year

Genetic predisposition to antibiotic-associated deafness. PIs Maria Bitner-Glindzicz and Shamima Rahman. £30,167

2007 - 2012

Great Ormond Street Hospital Children’s Charity, Research Leadership award

Mitochondrial disease identification. PI, Shamima Rahman. £272,787

2007 - 2012

DH/HEFCE, Senior lectureship, 5 years

Integrated clinical and research centre for patients of all ages with mitochondrial disorders. PI, Shamima Rahman. £238,870

Doctor Veronica Kinsler

Doctor Veronica Kinsler

Email

Telephone Number:  0207 905 2876

Publications

Background

I am a academic Paediatric Dermatologist working between the UCL Institute of Child Health and Great Ormond St Hospital.  I investigate the genetic basis of rare Paediatric Dermatology conditions, with a particular focus on pigmentary, neurocutaneous and mosaic disorders.  The long-term aim of the research programme is to develop treatments for these currently untreatable diseases.

Main Interests/Achievements

Congenital melanocytic naevi (CMN): Long-term research project into all   aspects of multiple CMN and CMN syndrome that has led to delineating the cutaneous and non-cutaneous clinical phenotype, and finding the genetic basis of the condition.  For this the group received two nationally-contested prizes in 2013 (from the Academy of Medical Sciences, and the British Association of Dermatologists).  This project has moved forward into investigating potential medical therapies.

Malignant melanoma:  As CMN predisposes to malignant melanoma in childhood the group is also using findings in the CMN cohort to investigate the genetic basis of melanoma in the general population. 

Other pigmentary and/or mosaic disorders: The genetic basis of other rare pigmentary and mosaic disorders is being elucidated using candidate gene approaches and next generation sequencing.

Arterio-venous malformations: The group is undertaking a recent patient-led initiative to further research into the genetic basis of Arterio-Venous Malformations, a life-threatening condition for which the cause is not known and no substantial treatment is available.

GOSH Rare Dermatology Diseases Resource: the group runs this in-house tissue bank, to facilitate research into rare paediatric skin disorders.

Grants (last 5 years/current)
2014 - 2015 SPARKS charity - A novel small molecule kallikrein 5 inhibitor - a promising target for the treatment of atopic dermatitis.  Co-applicant. £85,983
2013 - 2015

Butterfly AVM charity

The genetic basis of Arterio-venous malformations.  PI. £56,456

2013 - 2014 Livingstone Skin Research Centre, BRC funding 2014-2015
UCL Institute of Child Health.  £137,000
2009 - 2012

Wellcome Trust Research Fellowship

Investigation of the genetics and the phenomenon of spontaneous

involution of giant Congenital Melanocytic Naevi, £220,755

2011 - 2014 Caring Matters Now,
The genetics of congenital melanocytic naevi, Principal Investigator. £70,000

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