Overview
James joined the monogenic diabetes team at Exeter as a PhD student in December 2021. His interest in monogenic diabetes stemmed from studying the genetics of rare diseases during his MSc in bioinformatics, completed at Cardiff University. In his PhD he is studying monogenic diabetes genetics under the tutelage and supervision of Dr Elisa De Franco, Prof Sarah Flanagan, Dr Matthew Johnson and Dr Matthew Wakeling.
James’ background in bioinformatics also means he is proficient in the development of pipelines to process and analyse genomics data, with particular experience in working with next generation sequencing (NGS) data. For his MSc dissertation project, James developed two Nextflow single-cell RNA-seq (scRNA-seq) pipelines based on different scRNA-seq quantification tools.
Qualifications
- BSc (hons) Zoology (Cardiff University)
- MSc Bioinformatics (Cardiff University)
Research
Research interests
James’s research interests focus on the genetics of rare diseases. Currently on his PhD, he is studying the genetic causes of neonatal and early onset diabetes. Through the use of next generation sequencing and other genomic methods, he hopes to identify novel genetic causes of these monogenic forms of diabetes.
James is also fascinated by the mechanisms by which deleterious genetic variants manifest as a disease phenotype. In particular, he enjoys learning about the knock-on effects of deleterious variants on gene regulatory networks and chromatin accessibility.
Research projects
- Defining the genetic causes of neonatal and early onset diabetes.
Publications
Key publications | Publications by category | Publications by year
Publications by category
Journal articles
Russ-Silsby J, Patel KA, Laver TW, Hawkes G, Johnson MB, Wakeling MN, Patil PP, Hattersley AT, Flanagan SE, Weedon MN, et al (2023). The Role of ONECUT1 Variants in Monogenic and Type 2 Diabetes Mellitus.
DiabetesAbstract:
The Role of ONECUT1 Variants in Monogenic and Type 2 Diabetes Mellitus.
ONECUT1 (also known as HNF6) is a transcription factor involved in pancreatic development and beta-cell function. Recently, biallelic variants in ONECUT1 were reported as a cause of neonatal diabetes mellitus (NDM) in 2 subjects and missense monoallelic variants were associated with type 2 diabetes and possibly maturity-onset diabetes of the young (MODY). Here we examine the role of ONECUT1 variants in NDM, MODY and Type 2 diabetes in large international cohorts of subjects with monogenic diabetes and >400,000 subjects from UK Biobank. We identified a biallelic frameshift ONECUT1 variant as the cause of NDM in one individual. However, we found no enrichment of missense or null ONECUT1 variants among 484 individuals clinically suspected of MODY, in whom all known genes had been excluded. Finally, using a rare variant burden test in the UK Biobank European cohort, we identified a significant association between heterozygous ONECUT1 null variants and type 2 diabetes (P=0.006) but did not find association between missense variants and type 2 diabetes. Our results confirm biallelic ONECUT1 variants as a cause of NDM and highlight monoallelic null variants as a risk factor for type 2 diabetes. These findings confirm the critical role of ONECUT1 in human beta-cell function.
Abstract.
Author URL.
Publications by year
2023
Russ-Silsby J, Patel KA, Laver TW, Hawkes G, Johnson MB, Wakeling MN, Patil PP, Hattersley AT, Flanagan SE, Weedon MN, et al (2023). The Role of ONECUT1 Variants in Monogenic and Type 2 Diabetes Mellitus.
DiabetesAbstract:
The Role of ONECUT1 Variants in Monogenic and Type 2 Diabetes Mellitus.
ONECUT1 (also known as HNF6) is a transcription factor involved in pancreatic development and beta-cell function. Recently, biallelic variants in ONECUT1 were reported as a cause of neonatal diabetes mellitus (NDM) in 2 subjects and missense monoallelic variants were associated with type 2 diabetes and possibly maturity-onset diabetes of the young (MODY). Here we examine the role of ONECUT1 variants in NDM, MODY and Type 2 diabetes in large international cohorts of subjects with monogenic diabetes and >400,000 subjects from UK Biobank. We identified a biallelic frameshift ONECUT1 variant as the cause of NDM in one individual. However, we found no enrichment of missense or null ONECUT1 variants among 484 individuals clinically suspected of MODY, in whom all known genes had been excluded. Finally, using a rare variant burden test in the UK Biobank European cohort, we identified a significant association between heterozygous ONECUT1 null variants and type 2 diabetes (P=0.006) but did not find association between missense variants and type 2 diabetes. Our results confirm biallelic ONECUT1 variants as a cause of NDM and highlight monoallelic null variants as a risk factor for type 2 diabetes. These findings confirm the critical role of ONECUT1 in human beta-cell function.
Abstract.
Author URL.
James_Russ-Silsby Details from cache as at 2023-09-26 13:56:26
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