Professor Andrew Crosby
Professor of Human Genetics
Neuroscience and Neurology
Wellcome Wolfson Centre, RILD Institute, University of Exeter Medical School
Skills Development Fellowship Vision
To provide the opportunity for an individual to further develop their research ideas, skills and portfolio, as well as their academic attributes and experiences, to enable them to establish an independent academic career in an area of clinically-impacting research. As sponsors our group would aim to support career development in the area of genomic medicine in which knowledge gleaned from genetic and molecular studies may be applied to drive effective diagnostic, and ultimately novel therapeutic, interventions. Developing meaningful and lasting interdisciplinary collaborative relationships is crucially important in modern academic life, and the candidate would be encouraged and supported in establishing such relationships nationally and internationally.
I have substantial experience in sponsoring career development and other fellowships, having personally supervised 46 Postgraduate level studentships (20 PhD/MD studentships – 9 of which involve clinical students – as well as 26 MSc/MRes/MByRes). Through this experience I have developed a deep understanding of how to support individuals in embarking on a successful academic career. The specific path each fellow may follow will depend upon the interests, motivations and experiences particular to the candidate involved. I and my colleagues will be very happy to meet with candidates to provide guidance and advice towards developing a successful fellowship.
Prior to my arrival in Exeter in 2013 I was Joint Departmental Head of the Genetics Research Centre at St. George’s University London (Oct 2010-June 2013), and prior to that Birth Defects Foundation Reader in Medical Genetics, St. George’s University London (Oct 2005-Oct 2010).
I work in close partnership with Dr Emma Baple as part of multiple international consortia whose overarching objectives are to utilise molecular and functional research studies, combined with clinical expertise, to identify novel molecular mechanisms of disease and provide crucial scientific insight into disease pathogenesis. This work involves in-depth molecular studies to define new genetic and molecular causes of inherited conditions, particularly inherited neurological and ocular disorders. We aim to translate findings from this work into improved diagnostic services, therapeutic interventions and healthcare outcomes alongside increased understanding and awareness of inherited disease within the community setting.
Our work primarily involves the investigation of rare inherited conditions which occur in founder communities such as the Amish, and in rural communities in Pakistan and Oman. In these communities, ancestral founder mutations typically accumulate due to regional marriage patterns and are associated with a high frequency of inherited conditions. This enables empowered genetic studies to define the molecular causes of these conditions, as well as expansive clinical evaluations to precisely define clinical outcomes.
- Choline transporter mutations in severe congenital myasthenic syndrome disrupt transporter localization. (2017) Wang H, Salter C, Refai S, Hardy H, Barwick KES, Akpulat U, Kvarnung M, Chioza BA, Harlalka G, Taylan F, Sejersen T, Wright J, Zimmerman HH, Karakaya M, Stüve B, Weis J, Schara U, Russell MA, Chilton J, Blakely RD , Baple EL, Cirak S,Crosby AH. Brain, in press
- A partially inactivating mutation in the sodium-dependent lysophosphatidylcholine transporter MFSD2A causes a non-lethal microcephaly syndrome (2015). Alakbarzade V, Hameed A, Quek DQY, Chioza BA, Baple EL, Cazenave-Gassiot A, Sreekantan-Nair A, Weedon MN, Rich P, Patton MA, Warner TT, Silver DL, Crosby AH. Nature Genetics, 138(Pt 8):2173-90.
- Hypomorphic PCNA mutation underlies a human DNA repair disorder. (2014) Baple EL, Chambers H, Cross HE, Fawcett H, Nakazawa Y, Chioza BA, Harlalka GV, Mansour S, Sreekantan-Nair A, Patton MA, Muggenthaler M, Rich P, Wagner K, Coblentz R, Stein CK, Last JI, Taylor AM, Jackson AP, Ogi T, Lehmann AR, Green CM, Crosby AH. J Clin Invest. 124(7):3137-46
Ongoing Projects & Grants
My main area of research focus involves defining the genetic and molecular basis of inherited neurological disease, in order to provide important mechanistic insight into the disease mechanism to develop therapeutic intervention. This work has a particular focus on neurodevelopmental disorders, as well as motor neurone disease(s).
My group’s studies utilise cutting edge genomic approaches to define new genes which, when mutated, may give rise to these conditions. Our genetic investigations to define new molecular causes of inherited disease are greatly empowered by our involvement in a series of long-running overseas community-based research programmes, such as the Amish. These research programmes further benefit from our established collaborative links with large-scale UK as well as international gene sequencing research programmes, with whom we routinely exchange information.
Further to our genetic studies we also undertake specialist functional studies stemming from our genetic discoveries to more deeply probe the molecular basis of each condition. These studies typically involve a wide range of established (cell and protein studies) methodologies as well as more advanced iPSC and animal models of disease.
This programme of research is supported by a wide body of active grants from Research Councils (MRC), Charities (MRF, Newlife, Fight for Sight, The Spastic Paraplegia Foundation), and the Wellcome Trust.
Key academic collaborators for genomic studies include Jim Lupski (Baylor College Medicine, USA), Fowzan Alkuraya (King Faisal Institute, Saudi Arabia) and Matt Hurles (Sanger Institute, UK) externally, and Sian Ellard and Caroline Wright in Exeter. In addition we collaborate extensively with national and international experts leading investigations into a range of cell, molecular and animal model functional studies. We also interface and work closely with a wide range of clinical colleagues who recruit families to our research programme and enable translation of the results directly back into improved patient care.
Research Group Connections