• PhD (University of Manchester)
• CCST in Clinical Genetics (UK)
• MRCPCH (UK)
• MBBS (University of Mumbai)

The aim of my work is to improve diagnosis, management and treatment of rare diseases. Rare diseases pose a significant medical and societal challenge because they affect ~5% of the population. A vast majority of rare diseases are genetic in origin. Rare Diseases are often difficult to define, diagnose, manage and treat.

I am a Clinician Scientist who combines genomics with functional and clinical studies in rare human genetic disorders. My primary research interest is in neurodevelopmental and congenital malformation disorders, mainly those caused by defects in chromatin regulation and the non-coding genome, including small nuclear RNAs. My group has led, or contributed to, the discoveries of more than 50 novel genetic diseases. Using a combination of cellular and organismal models and benefiting from extensive internal, national and international collaborations we have defined underlying mechanisms of several rare disorders. I have experience in leading international collaborations for development of expert consensus management guidelines for rare diseases and interventional clinical trials in rare diseases.  My research has a direct and immediate impact on health by improving diagnosis, management and treatments for patients, while simultaneously revealing fundamental biological insights.

I addition to my role at the University, I am also a Consultant Clinical Geneticist Manchester Centre for Genomic Medicine at the Manchester University NHS Trust. In my clinical prcatice I see children and adults with a range of genetic disorders.

I am the Founding Clinical Director of the Manchester Rare Conditions Centre. The MRCC is a platform that aims to improve the lives of people with Rare Conditions of all ages. The MRCC has four themes - Clinics & Diagnostics, Research & Innovation, Education & Training, and Advocacy & Engagement.

I Co-Direct the MRC/NIHR EpiGenRare Node in the UK Rare Disease Paltform along with Prof Albert Basson. The aim of this node is to perform ground breaking research in the field and to bring together a collaborative community of researchers, clinicians and patients and public organisations.

I Co-lead the Rare Conditions theme of the NIHR Manchester Biomedical Research Centre along with Prof Bill Newman. This Theme has three work programs - Improving diagnosis, understanding and prevention of rare conditions; Understanding the impacts and outcomes of rare conditions; Identifying novel treatments for rare conditions.

I co-lead NHS Rare Disease & Functional Genomics Network of Excellence along with Prof Emma Baple and Prof Rob Taylor. The aim of this Network is to improve rare disease related clinical pathways, new diagnostic approaches, increasing efficiency of data analysis and increasing the capacity for clinical trials.

I am Academic Program Lead in the NIHR Manchester Integrated Academic Training program for Clinical Genetics Specialty and Rare Conditions Theme  for Academic Clinical Fellows and Academic Clinical Lecturers. 

I graduated in Medicine (MBBS) from Lokmanya Tilak Medical College (University of Mumbai) in 2002, obtained Membership of Royal College of Paediatrics and Child Health (MRCPCH) in 2006 and joined Clinical Genetics training programme in Manchester in 2007. I was awarded a Research Training Fellowship by the NIHR Manchester Biomedical Research Centre from 2008 to 2011 and was awarded PhD by the University of Manchester in 2012. I obtained my Certificate of Completion of Specialist Training (CCST) in Clinical Genetics training in 2013 and was subsequently appointed as Clinical Senior Lecturer and Consultant Clinical Geneticist in July 2013. I have been in my current position from 2021.

Identification of novel diseases

We perform analyse large-scale multi-omic and clinical data to identify novel genetic diseases, especially chromatinopathies, spliceosomopathies, neurodevelopmental disorders and congenital malformations. We have led on, or played a major role in, the identification of several rare genetic diseases and uncovered their mechanisms.

• RNU2-2-related Neurodevelopmental disorder (OMIM 621304)
• RNU5B-1-related Neurodevelopmental disorder (OMIM 621302)
• TUFT1-related Wolly hair skin fragility syndrome (OMIM  620415)
  
• ATP6V0C-related Early-onset epilepsy with or without developmental delay Type 3 (OMIM 620465)
  
• Non-coding Xq26.1 dupliations-related Bazex-Dupre-Christol syndrome (OMIM 301845)
• FRA10AC1-related Neurodevelopmental disorder with growth retardation, dysmorphic facies, and corpus callosum abnormalities (OMIM 608866)
• Activating RAC1 variants-related neurodevelopmental syndrome (OMIM awaited)
• ERBB4-related neurodevelopmental disorder (OMIM awaited)
• EIF5A-related Faundes-Banka syndrome (OMIM 619376)
• KMT2D ex 38/39 missense variants-related Branchial arch abnormalities, choanal atresia, athelia, hearing loss, and hypothyroidism syndrome (OMIM 620186)
• TET3-related Beck-Fahrner syndrome (OMIM 618798)
• PCYT2-related Autosomal recessive Spastic Paraplegia 82 (OMIM 602679)
• ATP6V0C haploinsufficiency driven 16p13.3 deletion syndrome (OMIM awaited)
• KMT2E-related O'Donnell-Luria-Rodan syndrome (OMIM 618512)
• KDM5B-related autosomal recessive developmental disorder (OMIM 618109)
• KMT5B-related dominant overgrowth syndrome (OMIM 617788)
• KMT2C-related dominant developmental disorder (OMIM 617768)
• KMT2B-related dominant developmental disorder type 68 (OMIM 619934)
• ASH1L-related dominant developmental disorder (OMIM 617796)
• ACTB deletions, nonsense and frameshift mutations related dominant pleiotropic disorder (OMIM 243310)
• RAC1-related intellectual disability (OMIM 602048)
• POU3F2 encompassing 6q16.1 deletions-related Obesity and intellectual disability 
• 8q22.1 duplicaitons-related Leri's pleonostoesis (OMIM 151200)
• G6PC3-related Dursun syndrome (OMIM 612541)
• DHFR-related Dihydrofolate reductase deficiency (OMIM 613839)

We have also contributed to collaborative projects leading to the discoveries of following diseases -

• GLTP-related Icthyosis (OMIM awaited)
• RCC1-related Acute onset axonal neuropahy (OMIM 621333)
• DHRS3-related Craniosynostosis-scoliosis syndrome (OMIM 621499 )
• DOT1L-related Nil-Deshwar neurodevelopmental syndrome (OMIM 621265)
• DAP3-related Perrault syndrome 7 (OMIM 621101)
• ZFX-related X-linked syndromic Intellectual developmental disorder type 37 (OMIM 301118)
• GTPBP1 and GTPBP2-related neurodevelopmental disorders (OMIM awaited)
• CRELD1-related Jeffries-Lakhani neurodevelopmental syndrome (OMIM 620771)
• DOT1L gain of function-related Nil-Deshwan neurodevelopmental syndrome (OMIM 621265)
• LNPK-related Neurodevelopmental disorder with epilepsy and hypoplasia of the corpus callosum (OMIM 612036)
• HNRNPC-related Intellectual developmental disorder, autosomal dominant 74 (OMIM 620688)
  
• EZH1-related neurodevelopmental disorder (OMIM awaited)
• ERI1-related Guo-Campeau type spondyloepimetaphyseal dysplasia (OMIM 620663)
• KDM6B-related Stolerman neurodevelopmental syndrome (OMIM 611577)
• AMFR-related Autosomal recessive spastic paraplegia 89 (OMIM 603243)
  
• FILIP1-related Neuromuscular disorder, congenital, with dysmorphic facies (OMIM 607307)
  
• EIF4A2-related Neurodevelopmental disorder with hypotonia and speech delay, with or without seizures (OMIM 601102)
• TMEM147-related intellectual disability, facial dysmorphism and pseudo Pelger-Huet anomaly (OMIM 613585)
  
• PCDHGC4-related  Neurodevelopmental disorder with poor growth and skeletal anomalies (OMIM 606305)
  
• ARFGEF1-related Developmental delay, impaired speech, and behavioral abnormalities, with or without seizures (OMIM 604141)
  
• BCAS3-related Hengel-Maroofian-Schols syndrome (OMIM 619641)
  
• SPEN-related Radio-Tartaglia syndrome (OMIM 619312)
  
• SATB1-related Developmental delay with dysmorphic facies and dental anomalies (OMIM 619228) and Kohlschutter-Tonz syndrome-like syndromes (OMIM 619229)
  
• Acivating TRIO missense variants related autosomal dominant intellectual developmental disorder type 63 with macrocephaly (OMIM 618825)
  
• CACNA1B-related Neurodevelopmental disorder with seizures and nonepileptic hyperkinetic movements (OMIM 618497)
  
• CACNA1E-related Developmental and epileptic encephalopathy type 69 (OMIM 618285)
• CHD3-related Snijders Blok-Campeau syndrome  (OMIM 618205)
  
• CYFIP2-related Developmental and epileptic encephalopathy 65 (OMIM 618008)
  
• ITPR1-related Gillespie Syndrome (OMIM 206700)
• TBC1D24-related DOORS syndrome (OMIM 220500)
  
• EZH2-related Weaver syndrome (OMIM 277590)
  
• PRDM5-related brittle cornea syndrome type 2 (OMIM 614161) 

Uncovering rare-diseases mechanisms

In collaboration with several research groups, locally and internationally, we have used cellular and organismal models to understand mechanisms of several diseases that has provided insights into fundamental biological processes (e.g. nuclear role of beta-actin and the role of POU3F2 in the neuroendocrine pathway for appetite); showed the diversity of disease causing genetic mechanisms (e.g. extreme phenotypic variability in RAC1-associated intellectual disability) and highlighted link of rare disease genes with commoner conditions (e.g. Leri’s pleonosteosis and systemic sclerosis); and led to development of treatments for some rare disorders (e.g. folinic acid treatment for DHFR deficiency).

Current work: We are using induced pluripotent stem cells (iPSCs) to study the basis of neuroloical disease (differentiating into cortical neurons) and malformations (differentiating into neural crest cells) in diseases caused by KMT2D mutations (with Prof Sue Kimber); Drosophila models to study the mechanism of RAC-related disorder (with Dr Tom Millard); zebrafish models to study EIF5A, FKBP4 and RLF-related disorders (with Dr Paul Kasher); mice models to study ACTB-related disordes (with Prof Adrian Woolf).    

Clinical and molecular spectrum characterisation and guidelines development

Knowing phenotypic spectrum of rare conditions is crucial for their diagnosis and management. We have led on, or played a major role in, clinical characterisation of the following diseases -

• TSPEAR-related Ectodermal dysplasia 14 (PMID 37009414)
  
• KMT5B-related dominant overgrowth syndrome (PMID 36897941)
• Diseases caused by variants in genes encoding basement membrane components (PMID - 35584218)
• TMEM260-related Structural heart defects and renal anomalies syndrome (PMID - 34612517)
• SETD1B-related intellectual developmental disorder with seizures and language delay (PMID - 34345025)
• KCNT2-related Developmental and epileptic encephalopathy 57 (PMID - 34061450)
• KDM6A-related X-linked Kabuki syndrome Type 2 (PMIDs - 33674768 and 24527667)
• BCAT2-related Hypervalinemia or hyperleucine-isoleucinemia (PMID - 31177572)
• Exon 30/31 CREBBP missense variants related Menke Hennekam syndrome (PMID - 30892814, 38553851 and 39306848)
  
• KMT2D and KDM6A related Kabuki syndromes (PMID - 30514738)
  
• We have published the largest studies on Type 1 and Type 2 Kabuki syndromes, one of the commonest chromatin developmental disorders.
• INPP5E-related Joubert syndrome type 1 and MORM syndrome (PMID 26748598)
• TPK1-related episodic encephalopathy thiamine metabolism dysfunction (OMIM 614458) and Leigh syndrome. We also showed that timely treatment with thiamine supplementation improves outcome (see details).
• We have shown that G6PC3 deficiency occurs in a phenotypic continuum and is characterized by severe congenital neutropenia with other haematological, urogenital and cardiovascular defects (see details).

We have also contributed to clinical characterisation of -

• RBL2-related Brunet-Wagner neurodevelopmental syndrome (PMID - 39692517)
• FZD5-related eye malformation (PMID - 36695497)
  
• GBA1-related Gausher syndrome (PMID - 36537898)
  
• Urorectal septum malformation syndrome (PMID - 36478354)
• CLCN4-related Raynaud-Claes syndrome (PMID - 36385166)
  
• SPTAN1-related neurogenetic disorders (PMID - 36331550)
• Variants in BMP signalling pathway in lambdoid craniosynostosis (PMID 35997807)
• Monogenic disorders mimicking juvenile idiopathic arthritis (PMID 35717242)
• Exon 38/39 KMT2D misense variants related Branchial arch abnormalities, choanal atresia, athelia, hearing loss, and hypothyroidism syndrome (PMID - 35060672)
• Robinow syndrome (PMID 35047859)
• HYAL2 deficiency (PMID 34906488)
• Gaucher diseases (PMID 34649574)
• GRIN1-related Developmental and epileptic encephalopathy (PMID 34611970)
• Non-coding MEF2C disease-causing variants (PMID 34022131)
• DHX30-related neurodevelopmental disorder (PMID 34020708)
• MED12-related neurodevelopmental disorders (PMID 33244165)
• CYFIP2-related developmental and epileptic encephalopathy 65 (PMID 33149277)
• THOC2-related X-linked neurodevelopmental disorder (PMID 32116545)
• CUBN-related Imerslund-Grasbeck syndrome (PMID 31497480)
• HIST1H1E-related Rahman syndrome (PMID 31400068)
• COL13A1-related Congenital myasthenic syndrome type 19 (PMID 31081514)
• KMT2A-related Wiedemann-Steiner syndrome (PMID 30159147)
• AIRE-related Autoimmune polyendocrinopathy type 1 (PMID 26084028)
• KAT6B-related neurodevelopmental disorders (PMID 25424711)
• TNNT3-related distal arthropgryposis type 2B2 (PMID 25337069)
• EZH2-related Weaver syndrome (PMID 24214728)
• PMP22-related Charcot-Marie-Tooth disease type 1A (PMID 22996176)
• Trisomy 18 (PMID 22105572) 

Functional Genomics and Advanced Diagnostics

In collaboration with EpiSigns, we have established DNA methylation arrays as a diagnotic service for rare diseases (EpiPro Project). We have also used this approach for disease identification and characterisation in research. See examples of our own and collaborative works - PMID 35904121, 35506254, 35047860, 34750377, and 31949313.

Clinical Trials

We have run clinical trials for rare diseases. See examples -

• A Novel, Regulated Gene Therapy (NGN-401) Study for Females With Rett Syndrome

• Double-blind randomised placebo-controlled dose escalation safety, tolerability and efficacy study of Blarcamesine in children with Rett syndrome 

• Double-blind randomised placebo-controlled dose escalation safety, tolerability and efficacy study of Blarcamesine in adults with Rett Syndrome

• Clinical Genetics Society (UK) - Academic Vice President
• British Society of Genomic Medicine
• European Society of Human Genetics
• American Society of Human Genetics
• British Inherited Metabolic Diseases Group
• Skeletal Dysplasia Group
• Royal College of Paediatrics and Child Health
• General Medical Council

Postgraduate University Courses

• MRes Precision Medicine (previously Translational Medicine) project supervisor.
• MSc Genomic Medicine project supervisor.
• MRes Bioinformatics and Systems Biology project supervisor.
• Faculty for PGCert Clinical Genetics and Genetic Counselling (Beijing).
• Previous Program Director and Pathway lead for the national Genomics Scientist training program (STP) MSc.
• Previous Clinical lead of ‘Omics Techniques and their Application to Genomic Medicine’ Module for MSc Genomic Medicine at the University of Manchester.

Undergraduate University Courses

• Development and Delivery Lead for Genetics courses in the Lancaster University Medical School.
• Faculty for Clinical Genetics modules for 4th Year Manchester Medical School. 
• APEP project supervisor

Specialist International Courses

• Co-organizer of the annual European Society of Human Genetics Manchester Dysmorphology course.
• I regularly organise or teach at various international specialty training courses.

Post-doctoral Research Associates

• Dr Sara Cuvertino (Pluripotent stem cell models of KMT2-diseases, GOSH-Sparks)
• Dr Natalie Chaddock (Advanced data analysis and multi-omic approaches for diagnosis and discovery of rare conditions, NIHR Manchester Biomedical Research Centre)
  
• Dr Rebecca Yarwood (Zebrafish models of neurodegenerative disorders of Kennedy pathway, MRC)
  

 Current PhD (or equivalent) students (Primary supervisor)

• Andrew Fleming (Long read genomic technologies for diagnosis of rare diseases, DClinSci)
• Kedar Bhosale (Unveiling the molecular basis of chromatinopathies to delineate innovative therapeutic solutions, Marie Curie DTP, UKRI)
• Dr Alex Blakes (Gene termini variants in human diseases, Wellcome 4WardNorth doctoral training program)
• Jacob Sampson (Regulatory variants in human diseases, MRC doctoral training program)
  
• Shige Wang (Understanding and treating neurogenetic disorders caused by defects in the Kennedy pathway, China Scholarhip Council)
  
• Evgenii Martirosian (Genomics and epigenomics of rare diseases, BRC Theme PhD studentship)
• Ankur Charasia (Genomics of Developmental Disorders in India, GCRF)

Current PhD (or equivalent) students (Co-supervisor)

• Ana Piers Piedade (NIHR Manchester BRC Core PhD studentship)
• Oliver Cooper (NIHR Manchester BRC Theme PhD studentship)
• Aoife O'Sullivan (NIHR Manchester BRC Theme PhD studentship)
• Thomas Wright (NIHR Manchester BRC Theme PhD studentship)
• Hulia Van Campen (DClinSci)
• Hebah Al Thebaiti (University of Jeddah scholarship)
  
• Celia Duff-Farrier (DClinSci)
  
• Hilmar Orn Gunnlaugsson Nielsen (University of Iceland)
• Carolina Stambouild (MRC DTP)

Past PhD (or equivalent) students (Primary supervisor)

• Andrew Thom 2024 (Non-muscle actinopathies, Marsh studentship) - Now Research Technician at the University of Manchester
• Dr Adam Jackson 2023 (Solve-RD, H2020) - Now Academic Clinical Fellow in Clinical Genetics, Manchester Centre for Genomic Medicine.
  
• Emma Stevenson 2023 (Laboratory diagnosis of cobalamin deficiency, DClinSci) - Now Principal Clinical Scientist in Biochemistry at Gloucestershire Hospitals NHS Trust
• Ronnie Wright (Solving the unsolved via WGS, DClinSci) - Now Deputy Lead Rare Diseases Genomics, Manchester Univeristy Hospitals NHS Trust - Now Rare Disease lead at the NHS North West Genomics Laboratory Hub
• Dr George Burghel 2022 (Improving interpretation of CNVs, DClinSci) - Now Deputy Lead Cancer Genomics, Manchester Univeristy Hospitals NHS Trust
• Dr Victor Faundes Gomez 2019 (Histone lysine methylases and demethylases in developmental disorders) - Now Assistant Professor at University of Santiago, Chile.
  

Past PhD (or equivalent) students (Co-supervisor)

• Rob Harkness 2023 (Wellcome DTP) - Now Post-Doctoral Research Associate at the university of Manchester.
  
• Dr Aimee Donald 2019 (Gaucher syndrome) - Now NIHR Academic Clinical Lecturer in Paediatric Neurology, Manchester.

 Collaborators

• Prof Bill Newman (NIHR Manchester BRC Rare Conditions theme)
• Prof Albert Basson (MRC/NIHR EpiGenRare)
• Prof Sue Kimber (iPSC models of KMT2-diseases; Manchester; Funded by GOSH-Sparks)
• Prof Martin Lowe (Zebrafish models of Kennedy pathway disorders; Manchester; Funded by Spastic Paraplegia Foundation, USA)
• Prof Anna Nicolaou (Lipidomics of Kennedy pathway disorders; Manchester; Funded by Spastic Paraplegia Foundation, USA)
• Dr Tom Millard  (Drosophila models of RAC-related disorder; Manchester)
• Dr Paul Kasher (Zebrafish models of EIF5A, FKBP4 and RLF-related disorders; Manchester; Funded by MRC DTP and H2020)
• Prof Adrian Woolf (Mice models of ACTB-related disordes; Manchester; Funded by Marsh studentship)
• Dr Adam Stevens (Systems biology of chromatin disorders; Manchester; Funded by GOSH-Sparks)
• Prof Graham Pavitt (Yeast models of EIF5A; Manchester; Funded by MRC DTP)
• Prof Colin Johnson (Ex38/39 KMT2D MV disorder; Leeds)
• Prof Girish Katta (Genomics of Developmental Disorders in India; Manipal, India; Funded by Global Challenges Research Fund)
• Dr Nataliya Di Donoato (ACTB-related disorders; Dresden, Germany; Funded by Marsh studentship)
  
• David Gokhale (DNA methylation based diagnostics for rare diseases; Funded by GMSA)

• Dickinson Trust Travel award in 2014 for travel to John Hopkins Institute (USA) in June 2015.
• ESHG National Fellowship to attend the ESHG annual conference 2012 in Nuemberg, Germany.
• Distinguished Achievement Medal – Post Graduate Student of the Year (2012) awarded by the Faculty of Medical and Human Sciences, University of Manchester.
• 2011 Founder’s award for the best presentation at the Skeletal Dysplasia Group Meeting.
• Dame Barbara Clayton Memorial award for best trainee presentation at British Inherited Metabolic Diseases Group Annual Symposium 2011.
• Best Presentation at the 2011 Research Showcase of School of Biomedicine, University of Manchester.
• ESHG Poster Award for an outstanding presentation at the European Society of Human Genetics Conference 2011.
• Robin Winter Prize for best presentation by a trainee at the 2011 Clinical Genetics Society of UK Annual Spring Conference.
• Travel Scholarship from Society for the Study of Inborn Errors of metabolism to attend SSIEM 2011 Annual Symposium in Geneva.
• Travel Bursary from the European Paediatric Neurology Society to attend the EPNS conference 2011, Cavtat.
• Wellcome Trust Bursary to attend Genomic Disorders 2011 – The Genomics of Rare Diseases Conference, Cambridge.
• Research Councils UK-India Early Career Researchers’ Travel Funding to attend the Indian Society of Human Genetics Annual Conference 2011, Manipal.
• British Society of Human Genetics Travel Award to attend Society for Study of Inborn Errors of Metabolism Annual Symposium 2010, Istanbul.
• Dickinson Trust Travel award for 2008 to attend ESHG course on Genetic Epidemiology in Paris.