Bill is Professor of Translational Genomic Medicine in The Manchester Centre for Genomic Medicine at the University of Manchester and Honorary Consultant at Manchester University NHS Foundation Trust

President, European Society of Human Genetics (2024-25)

Clinical Director NW Genomic Medicine Service Alliance

Co-Lead BRC Theme on Rare Conditions

Lead of NHSE Network of Excellence on Pharmacogenetics and Medicines Optimisation

I am a clinician scientist. I studied Medicine at Manchester University and completed professional training in adult medicine in the North West of England. I started training in Clinical Genetics in 1995 and undertook a PhD as a Wellcome Trust Clinical Training Fellow on the genetics of bone development and osteoarthritis in the Wellcome Trust Cell Matrix Centre. I moved to Toronto to undertake a two year Arthritis Society Fellowship with Professor Kathy Siminovitch where I worked on the genetic basis of rheumatoid arthritis and inflammatory bowel disease.

I took up my post as Clinical Senior Lecturer in Genetics at the University of Manchester and Honorary Consultant at St Mary's Hospital in 2004 and was awarded my Chair in 2013. My research has focussed on pharmacogenetics - defining the genetic factors that influence how patients respond to their medications and on rare inherited conditions and have discovered a number of genes responsible for a range of conditions, and complex mutational mechanisms that lead to these.

a) Understanding the causes of Rare Conditions

Using next generation sequencing, I have been working with clinical colleagues to define the genetic causes of a number of rare inherited conditions. Over the past decade I have led or contributed to the discovery of >25 conditions. With colleagues, I have research programmes on a number of rare conditions including Perrault syndrome (deafness and ovarian failure), lower urinary tract disorders and a novel form of infection triggered neuropathy. I am especially interested in using whole genome sequencing to determine how non-coding sequence variation contributes to these disorders. This work informs my co-leadership of the Rare Condition theme in the Manchester BRC.

b) Pharmacogenetics

I am interested in how patients respond to their medication.

I work closely with John McDermott (Genomic Medicine), Katherine Payne, Stuart Wright, Alex Thompson (Health Economics), Paul Wilson (Implementation Science), Mike Turner, Lu Shin Wong (Chemistry), Antony Adamson (Genomics) and Videha Sharma (Health Informatics) on clinical implementation of pharmacogenetics and how novel rapid genetic tests can improve outcomes.

I undertook an NIHR i4i grant (PALOH) working with colleagues in neonatal units in Liverpool and Manchester and Genedrive to use point of care genetic testing to avoid hearing loss in babies exposed to the antibiotic gentamicin. This work resulted in a NICE Early Value Assessment before national adoption and was awarded the New Statesman Healthcare Positive Impact Award 2022. This has now extended to a nationwide study (PALOH-UK) funded by NIHR-OLS.

Our ongoing studies in primary care (PROGRESS) and on rapid diagnostics (DEVOTE) have been funded by NHSE and Innovate UK, respectively.

c) Genetics of Lower Urinary Tract Malformations

With Adrian Woolf and Neil Roberts we have identified that genetic changes in the genes called HPSE2 (heparanase 2) and LRIG2 result in the inherited condition called urofacial (Ochoa) syndrome. This condition is characterised by an unusual facial expression and bladder and bowel voiding problems. We are studying how these genes are important for bladder development and ways to treat bladder problems in children. This work has expanded to study a rare disorder called bladder exstrophy. These studies have resulted in the recent award of a MRC-NIHR Rare Disease Node (REOLUT) with colleagues in London and Cambridge to form a network of researchers in this field.

d) Genetics of Perrault syndrome

Perrault syndrome is a rare inherited condition characterised by severe hearing loss and ovarian failure. Variants in many genes that alter mitochondrial function cause this condition. Working with Ray O'Keefe and Rob Taylor (Newcastle), our studies, funded by MRC and RNID, have identified many new genes (CLPP, MRPL49, PRORP and DAP3) that are associated with this complex condition. This work provides insight into the mechanisms that result in hearing loss and ovarian failure and potential routes to treatment.

e) Spliceosomal disorders

With Ray O'Keefe, we are using yeast, mouse and pluripotent stem cell studies to understand why children with variants in genes that code componenets of the spliceosome (important in RNA transcript processing) are affected by craniofacial disorders, including Burn McKeown syndrome.

Current Funding: NIHR, Innovate UK, MRC, NHSE

I was Chair of the Education Committee for the European Society of Human Genetics 2020-24.

With Profs Bart Loeys and Johan Saenen (University  of Antwerp) I have established a European Society of Human Genetics training course for health professionals in cardiac genetics 2016-present

With colleagues I established a PGCert in Clinical Genetics and Genetic Counselling with Peking University, Beijing, China

With Dr Forbes Manson I established an MRes in Genetic Medicine 2011-16. This supported the foundation of the MSc in Genomic Medicine 2015 - present. I lead a module with John McDermott on this MSc in pharmacogenetics.

I was the Programme Director for the Genomic Sciences Scientific Training Program (STP) for Genomic Counselling, and Genomics 2016

I undertake teaching to postgraduate doctors as part of core medical training and to Specialist registrars in Genetic Medicine.

Siddharth Banka (Rare Conditions - co-lead BRC theme)

Gareth Evans

Katherine Payne

Thomas Friedman (NIDCD, USA)

Ray O'Keefe

Rob Taylor (Newcastle)

Wyatt Yue (Newcastle)

David Long (UCL), Mel Chan (LMS, Imperial), Menna Clatworthy (Cambridge) Adrian Woolf & Neil Roberts (Manchester) - as pare of MRC-NIHR Rare Disease Node (REOLUT)

American Society of Human Genetics

European Society of Human Genetics

British Society of Genetic Medicine

Genetics Society

BSc (hons) Experimental Immunology and Oncology

MB ChB (hons)

MA Healthcare Ethics and Law

FRCP

PhD