OMB No. 0925-0001 and 0925-0002 (Rev. 09/17 Approved Through 03/31/2020) 

BIOGRAPHICAL SKETCH 

Provide the following information for the Senior/key personnel and other significant contributors.[Text Wrapping Break]Follow this format for each person.  DO NOT EXCEED FIVE PAGES. 

NAME: Oram, Richard Anthony 

eRA COMMONS USER NAME (credential, e.g., agency login):  

POSITION TITLE: Senior Lecturer in Diabetes and Nephrology 

EDUCATION/TRAINING  

INSTITUTION AND LOCATION	DEGREE  (if applicable)	Completion Date  MM/YYYY	FIELD OF STUDY
University of Oxford	BA	07/2001	Physiology
University of Oxford	BMBCh	07/2004	Medicine
University of Exeter	PhD	07/2014	Type 1 Diabetes

 

 

1. Personal Statement

 

My research interests and experience include the study of beta cell loss in type 1 diabetes, use of biomarkers, genetics and development of the type 1 diabetes genetic risk score (T1D GRS).  

 

During my Diabetes UK funded PhD in Exeter, I used a sensitive method of assessing beta cell function to demonstrate that most people with long duration T1D have residual beta cell function. This first analysis proved that very low concentration C-peptide in T1D represented functional beta cells and a subsequent population based assessment of endogenous insulin (UNITED) has allowed us to identify rare people with T1D with high levels of persistent beta cell function many years from diagnosis. The work has led to a $1.1m JDRF strategic research agreement (Dr Oram is Co-PI with 4 others) to study immune, genetic and clinical associations of preserved endogenous insulin in type 1 diabetes. Importantly we developed simple blood and urine methods to assess C-peptide that could easily be used to screen other cohorts.  

 

I have continued to show a career trajectory of original thinking with development of the type 1 diabetes genetic risk score (T1D GRS) as a method to easily and cheaply measure genetic risk as a single continuous variable that is composed of multiple measures of GWAS SNPs. A key finding in our original paper was that genetic risk can be combined with other factors to better classify diabetes. This work has rapidly been received with great enthusiasm with papers and accompanying editorials already published in Diabetes, Diabetes Care (2016, 2018, 2019, in press), the Lancet Diabetes and Endocrinology (2018), Plos Medicine (2018) and Nature Medicine (2020). This innovative approach of being able to easily and cheaply tag HLA and non-HLA risk has high translational impact as both a research tool to investigate and better understand the biology of T1D and as a future diagnostic test to predict T1D and discriminate T1D from T2D and MODY. 

 

I have continued to translate genetic risk scores for clinical use by developing a commercial biochip with a private company (Randox) with licensing agreement and launch of the first generation T1D GRS biochip in spring 2023.  

 

1. Positions and Honors

 

Positions 

2004-2005 House Officer Medicine, Royal Devon and Exeter Hospital, UK 

2005 House Officer Surgery, High Wycombe Hospital, UK 

2005-2008 SHO General internal medicine, Royal Devon and Exeter Hospital, UK 

2008-2011 NIHR Academic Clinical Fellow, Diabetes and Nephrology, University of Exeter, UK 

2011-2014 Diabetes UK Clinical Training Fellow, University of Exeter, UK 

2014-2015 Alberta Health Services Transplant Fellow, University of Alberta, Canada 

2015-2016 NIHR Clinical Lecturer, University of Exeter, UK 

2017- Diabetes UK Harry Keen Career Development Award, Senior Lecturer and Honorary Consultant, University of Exeter, UK 

 

Honors  

 

• 2023 St Geroge’s Clinical Neurscience Conference (best oral abstract P Loginovic) 

• 2022 University of Exeter Dean’s Individual Career Development Fund (for Masters student P Loginovic) 

• 2019 Alan Turing Institute Fellowship (for PhD student Seth Sharp*) 

• 2018 American society for human genetics “reviewer’s choice” abstract award (Seth Sharp*) 

• 2017 Diabetes UK Harry Keen Fellowship 

• 2016 Diabetes UK  in Lilly Clinical Science Poster Award(Runner up) 

• 2016 World Congress of Pediatric Gastroenterology “Poster of Distinction” (Justine Turner*) 

• 2015 European Diabetic Nephropathy Study Group best oral presentation  

• 2014 Diabetes UK Nick Hales Young Investigator award 

• 2011 Diabetes UK George Alberti Clinical Training Fellowship 

 

Invited Lectures: 

 

2023 

• Association of Clinical Pathologists (UK) “Screening for type 1 diabetes” 

• Xiangya International Diabetes and Immunology Forum 

• International genetics of Ankylosing Spondylitis meeting, “Predicting future autoimmune disease with genetic risk scores” 

• Finnish National Paediatric Diabetes meeting Keynote “Heterogeneity in type 1 diabetes” 

 

2022 

• ISPAD Abu Dhabi keynote debate “are genetic risk scores useful in type 1 diabetes” 

• Hong Kong National Diabetes meeting “Genetic risk scores in type 1 diabetes” 

• Finnish National Paediatric Diabetes meeting Keynote “Heterogeneity in type 1 diabetes” 

• Scottish Study Group for Diabetes “utility of T1D GRS for classification of diabetes” 

• EASD SGGD “Classification of Diabetes with genetic risk scores” 

• University of Alberta Grand Rounds “Can we predict the future?” 

• JDRF Canada population screening symposium/workshop: “use of genetic risk scores for T1D screening” 

2021 

• Qatar Precision Medicine and Functional Genomics conference “prediction of type 1 diabetes” 

• Danish Diabetes Foundation “use of T1D GRS in clinical care” 

• Australian Diabetes Association “T1D GRS for  prediction of type 1 diabetes” 

• Estonia gene forum “can we predict the future: genetic prediction of type 1 diabetes and celiac disease” 

• American Diabetes Association “the role of genetics in prediction of type 1 diabetes” 

• Broad institute MGH “genetic risk scores for disease classification and prediction” 

• Diabetes UK Annual professional conference “improved prediction and classification of type 1 diabetes using polygenic risk scores 

2020 

• Immunology of Diabetes Society Balloon Debate “in type 1 diabetes beta cells are dead”  

• Chinese University of Hong Kong research seminar “Genetic risk scores in type 1 diabetes; the impact of ethnicity on type 1 diabetes research” 

• Diabetes UK Annual Professional Conference “”What’s new in T1DM” in the ‘Genomics and precision medicine in diabetes’ session.  

2019 

• Sandford Health, Sioux Falls, South Dakota “Prediction of Type 1 diabetes” 

• International Congress of the European Society for Pharmacogenomics and Personalised Therapy, Seville, Faculty and invited speaker “Prediction and diagnosis of type 1 diabetes using genetic risk scores” 

• Wessex Endocrine and Diabetes Association Day, invited lecture “Prediction and diagnosis of T1D using genetic risk scores” 

• Levine-Riggs Diabetes Symposium, City of Hope Hospital, Pasadena, USA “Does the immune response against beta cells burnout with time? 

2018 

• SIDRA Medicine CUDOS Meeting, Qatar “Clinical and Research uses of Genetic risk scores” 

• Barbara Davis Centre, Denver, Colorado, USA “Big data to ask simple question in T1D research.”  

• Immunology of Diabetes Society “The use of Big data in T1D research”, London  

• American Diabetes Association Scientific sessions “Beyond Single Nucleotide Polymorphisms―Building on Knowledge of the Genetic Architecture of Diabetes” 

• Oxford Centre for Diabetes and Metabolism, University of Oxford, “Clinical and research uses of Genetic risk scores in common disease” 

2017 

• Hebrew University of Jerusalem, Israel, Diabetes Special Seminar “What we can learn from persistent beta cells in long duration Type 1 Diabetes” 

• University of Indiana, USA Special Seminar “Genetics of Type 1 Diabetes” 

• University of Chicago, USA, Kovler Diabetes Centre Special Seminar “Type 1 Diabetes Genetic Risk Scores” 

• Massachusetts General Hospital, Endocrine Grand Rounds “Genetics of Type 1 diabetes” 

• Diabetes UK Annual Professional Conference, UK “Emerging Leaders session” 

• Texas City Wide Endocrine Rounds, Houston, USA “Heterogeneity of T1D” 

• Pacific North West Research Institute, Seattle, USA “Clinical and research uses of the T1D- GRS’ 

• Alberta Transplant Institute Seminar Series, Edmonton, Canada “Clinical and research uses of Genetic risk scores in autoimmune disease” 

• Toronto City Wide Endocrine rounds, Toronto, Canada “Novel approaches to genetic risk in T1D” 

2016 

• Benaroya Research Institute, Seattle, USA, “Type 1 Diabetes”  

• JDRF and Welcome Trust Diabetes and Inflammation Laboratory, Cambridge UK.  “C-peptide and Genetic risk score in Type 1 diabetes”  

• nPOD annual meeting, Miami, USA. Invited lecture “Heterogeneity of age of diagnosis in T1D” 

• Royal London Hospital “C-peptide in Type 1 Diabetes and Genetic Risk Scores” 

• Munich Octoberfest Type1 Diabetes Symposium “Genetic risk score and early type 1 diabetes” 

• University of Florida, USA. “Exploring heterogeneity in type 1 diabetes” 

• Alberta Transplant Institute Seminar Series, University of Alberta, Canada.  “Using genetics to answer simple clinical questions” 

• nPOD annual meeting Tampa, Miami, USA. “Clinical and scientific relevance of preserved C-peptide in long duration type 1 diabetes”  

• GTC Bio Diabetes Summit, Cambridge MA, USA. “Endogenous insulin production in type 1 diabetes”  

 

 

 

 

1. Contributions to Science

 

Most people with longstanding type 1 diabetes are insulin microsecretors 

Background: T1D was thought to progress to absolute insulin deficiency 

Central Finding: The majority of people with even long duration T1D have some residual beta cell function. During my PhD I proved, with 2 studies, that most people with T1D have measureable serum and urine C-peptide and that levels increment after a meal. This demonstrated that most people with T1D have a few remaining functional beta cells. This raises the ongoing question of whether longstanding beta cell function in T1D represents persistent beta cells that have evaded immune attack, or alternatively represents a consistent replenishment of beta cells that are constantly being regenerated and destroyed. 

Influence: These studies had a dramatic impact on the field, and raised that question of the clinical and scientific relevance of persistent beta cell function. They have changed the way we study beta cell function in Type 1 diabetes. The work has led to a $1.1m JDRF strategic research agreement (Dr Oram is Co-PI with 4 others) to study immune, genetic and clinical associations of preserved endogenous insulin in type 1 diabetes. Importantly we have developed simple blood and urine methods to assess C-peptide that could easily be used to screen other cohorts. UNITED has allowed us to develop reference ranges for blood and urine C-peptide that can be used to define clinical outliers by their residual C-peptide and will enable us to screen other large groups of patients.  

 

1. A large, population based study confirms most people with long duration type 1 diabetes are insulin microsecretors. RA Oram, TJ McDonald, BM Shields, MM Hudson, MH Shepherd, S Hammersley, ER Pearson, AT Hattersley on behalf of the UNITED Team. Diabetes Care. 2015 Feb;38(2):323-8. doi: 10.2337/dc14-0871. Epub 2014 Dec 17. PubMed PMID: 25519449. 

1. The majority of patients with over 5 years of type 1 diabetes are insulin microsecretors and have functioning beta cells. RA Oram, AG Jones, REJ Besser, BA Knight, BM Shields, RJ Brown, AT Hattersley and TJ McDonald. Diabetologia. 2014 Jan;57(1):187-91. PMID 24248267. 

1. Meta-genome-wide association studies identify a locus on chromosome 1 and multiple variants in the MHC region for serum C-peptide in type 1 diabetes. Roshandel D, Gubitosi-Klug R, Bull SB, Canty AJ, Pezzolesi MG, King GL, Keenan HA, Snell-Bergeon JK, Maahs DM, Klein R, Klein BEK, Orchard TJ, Costacou T, Weedon MN; DCCT/EDIC Research Group, Oram RA, Paterson AD. Diabetologia. 2018 May;61(5):1098-1111. PubMed PMID: 29404672. 

1. Persistent C-peptide is associated with reduced hypoglycaemia but not HbA1c in adults with longstanding Type 1 diabetes: evidence for lack of intensive treatment in UK clinical practice?. Marren SM, Hammersley S, McDonald TJ, Shields BM, Knight BA, Hill A, Bolt R, Tree TI, Roep BO, Hattersley AT, Jones AG, Oram RA. Diabet Med. 2019 Apr 6;. doi: 10.1111/dme.13960. PubMed PMID: 30955221. 

 

 

 

A Type 1 Diabetes Genetic Risk Score (T1D GRS) can aid discrimination between type 1 and type 2 Diabetes, prediction of type 1 diabetes and investigation of etiology. 

Background: It is becoming increasingly difficult to distinguish between type 1 and type 2 diabetes, particularly because of the increasing amount of obesity in young people. It is important to get the right diagnosis because correct treatment is dependent on this (i.e. Type 1 patients require insulin injections whereas Type 2 diabetes patients are often best treated with tablets or diet). Additionally the autoimmune process in type 1 diabetes commonly starts many years before clinical presentation, and methods that use genetic risk and additional markers to identify people before diagnosis may enable early disease modifying intervention. 

Central Finding: A Type 1 diabetes genetic risk score provides a simple, cheap and accurate addition to discriminating between Type 1 and Type 2 diabetes and can be used for prediction of type 1 diabetes.  

Influence: This is an important addition to correctly classifying diabetes subtype. This work also led to subsequent work that has demonstrated T1D-GRS can also discriminate Type 1 diabetes from monogenic diabetes,  

Specific Role: I conceived the first key study, planned and performed analysis, and wrote the first paper with Mike Weedon. I have built on this work with ongoing funding to study rare groups identified by  

 

1. A Type 1 Diabetes Genetic Risk Score Can Aid Discrimination Between Type 1 and Type 2 Diabetes in Young Adults. RA Oram, K Patel, A Hill, B Shields, TJ McDonald, A Jones, AT Hattersley and MN Weedon. Diabetes Care. 2015 Nov 17. pii: dc151111 (epub ahead of print) PMID: 26577414. 

1. Analysing the frequency and phenotype of Type 1 diabetes throughout the first six decades of life: a cross-sectional analysis from the UK Biobank cohort study using an innovative genetic susceptibility-exclusion method. Thomas NJ, Jones SE, Weedon MN, Shields BM, Oram RA (joint senior), Hattersley AT. Lancet Diabetes Endocrinol. 2018 Feb;6(2):122-129. doi: 10.1016/S2213-8587(17)30362-5. Epub 2017 Nov 30. 

1. Development  and  standardization  of  an  improved  type 1  diabetes  genetic  risk  score  for  use  in  newborn  screening  and  incident  diagnosis  Sharp SA, Rich SS, Wood AR, Jones SE, Beaumont RN, Harrison JW, Schneider DA, Locke JM, Tyrrell J, Weedon MN, Hagopian WA*#, Oram RA*# Diabetes Care. 2019 Feb;42(2):200-207. doi: 10.2337/dc18-1785. PubMed PMID: 30655379; PubMed Central PMCID: PMC6341291. 

1. A Combined Risk Score Integrating Autoantibodies, a Genetic Risk Score and Family History Advances the Prediction of Type 1 Diabetes Among High-Risk Children. Lauric A. Ferrat, Kendra Vehik, Seth A. Sharp, Åke Lernmark, Marian J. Rewers, Jin-Xiong She, Anette-G. Ziegler, Jorma Toppari, Beena Akolkar, Jeffrey P. Krischer, Michael N. Weedon, Richard A. Oram* (joint senior), William A. Hagopian*, and the TEDDY Study Group**. Nature Medicine in press 2020 

 

 

Repeated measures such as home UCPCR and/or Beta2score are a novel method to assess Islet transplant function 

Background: Islet and pancreas transplant function is difficult to objectively measure and so it is hard to track when and why they are failing. 

Central Finding: A simple combined formula of fasting glucose, fasting C-peptide, HbA1c and insulin dose is a cheap simple, repeatable measure of beta cell function. 

Influence: This will change the way that islet transplants are monitored and may also improve monitoring post immunotherapy in intervention trails and in natural history studies of type 1 diabetes. 

Specific role: I designed and undertook a repeated home UCPCR study in UK islet transplant recipients. I jointly performed analysis in Beta2score study. 

 

1. Validation Of The BETA-2 Score: An Improved Tool To Estimate Beta-cell Function After Clinical Islet Transplantation Utilizing A Single Fasting Blood Sample. RA Oram* (joint first author), S Forbes*, A Smith, A Lam, T Olateju, S Imes, AJ Malcolm, AM James Shapiro, PA Senior. Am J Transplant. 2016 Mar 28. doi: 10.1111/ajt.13807. PMID: 27017888. 

1. Home Urine C-peptide Creatinine Ratio can be used to monitor islet transplant function. RA Oram, A Brooks, S Eckoldt, R Smith, P Choudary, P Johnson, M Rosenthal, M Rutter, S Forbes, TJ McDonald, JAM Shaw* and AT Hattersley*. Diabetes 2014 Jun;37(6):1737-40. doi: 10.2337/dc13-1266. Epub 2014 Mar 12. PMID: 24623023. 

 

 

Full publication list at:  

http://www.ncbi.nlm.nih.gov/sites/myncbi/149KdpZ_9njkL/bibliography/41298152/public/?sort=date&direction=ascending. 

 

 

1. Additional Information: Research Support and/or Scholastic Performance

 

>£5m in last 3 years as PI, and >£3m as CoI 

 

Ongoing Research Support 

1. 2023 Randox Clinical Training Fellowships in AKI and NAFLD CoI (~£600,000) 

1. 2023 MRC CiC Development of a coeliac prediction application PI (£25,000) 

1. 2022 NIHR programme development grant on screening for type 1 diabetes CoI 

1. 2022-2025 Randox R & D Improved Prediction of Autoimmuine disease with Genetic Risk Scores, PI, (£2.2m) 

1. 2022-2024 JDRF Clinical and Economic Optimization Platform for Type 1 Diabetes Screening ($538,011) 

1. 2022-2024 JDRF AL-DIAR1 “ROAD TO PREVENTION”: An Improved Combined Approach to Predict Type 1 Diabetes Risk in MENA Region through Scalable and Cost-effective Technologies, CoI ($300,000) 

1. JDRF 2022-2024 A Multi-task Learning Framework for Developing Genetic Risk Score (GRS) Models of T1D for Multi-Ethnic Population, Co, I ($300, 081) 

1. 2022-2025 JDRF Using genetics to better diagnose and treat adult onset T1D in multi ethnic USA population Co-I ($1.5m) 

1. 2021-2024 Helmsley Charitable Trust, Extreme Early Onset T1D, from observation to mechanism, PI ($1.6m) 

1. 2021-2026 NIH NIDDK APC Acute Pancreatitis Consortium, genetics lead for Indianapolis University subaward (CoI, as external collaborator) 

1. 2020-2023 Helmsley Charitable Trust “Stimulated glucagon as a novel biomarker of hypoglycemia in type 1 diabetes”, PI ($915k) 

1. 2020-2025 NIH R01 DK121843-01 Type 1 Diabetes Genetic Risk Score in TrialNet (CI Maria Redondo Baylor college of medicine, RO is Co-I and analysis lead, ($185 to Exeter) 

1. 2020 UK Medical Research Council Confidence in Concept University of Exeter, Development of a from blood T1D GRS biochip, PI (£40k) 

1. 2019-2022 JDRF Strategic Research agreement 3-SRA-2019-827-S-B Improved, cost effective prediction of type 1 diabetes in early life using combined prediction models ($530k) 

1. 2018-2022 Diabetes UK PhD Studentship, Prediction of T1D in early life using the T1D GRS, biomarkers, demographics and environmental exposures in a combined risk score. I designed the study and wrote the grant application. PI (£110k) 

1. 2018-2021 The Helmsley Charitable trust Breakthrough Grant, “Understanding beta-cell destruction through the study of EXtremely Early-Onset Autoimmune Diabetes (EXE-T1D, $750,000)”. Co-PI with Tim Tree Kings  

1. 2018-2022 BIRAX regenerative medicine initiative, “Do people with diabetes retain functioning beta cells and can they make more”. PI (joint with Yuval D’Or, Jerusalem, Total $400k, $100k to Exeter)  

1. 2017-2022 Diabetes UK Harry Keen Fellowship, Career Development award to study Extremely Early onset T1D. I wrote the grant and conceived of the study. ((£899k) 

1. 2015-2018 Diabetes UK “Developing a type 1 diabetes genetic risk score to get the right diagnosis and the right treatment for patients with diabetes.” I conceived of the study with Mike Weedon, was first author on the key paper leading to this grant, and helped write the UK-based grant whilst I was living in Canada. Co-I (with 7 others, 3 hours per week),  

 

Completed Research Support 

1. 2018-2019 UK Medical Research Council Confidence in Concept University of Exeter, “Towards better diagnosis of celiac disease using a Celiac Genetic Risk Score”. I have led the study design and analysis strategy for this project and developed the collaboration with both the University of Alberta (Prof Justine Turner) and Randox. Co-PI (with 2 others) 

1. 2017-2018 National Institute of Health, Administrative supplement to SEARCH study “use of the T1D-GRS to define diabetes subtype in young people with diabetes” (3UC4DK108173-01S1). I designed and wrote application for supplement with collaborators and SEARCH study committee. Exeter PI  

1. 2014-2017  JDRF Strategic Research Agreement, “Immune Predictors of preserved endogenous insulin secretion in type 1 diabetes”. I wrote the first draft of the application, and designed the strategy for defining extreme C-peptide. My original two high impact papers prompted the grant call and successful application. PI (with 4 others, 4 hours per week),  

1. 2016-2017 The Helmsley Foundation Breakthrough initiative grant, “Understanding beta-cell destruction through the study of Extremely Early-Onset Autoimmune Diabetes (EXE-T1D). I conceived the study, wrote the grant. PI with Tim Tree Kings (3 CoIs)  

1. 2015-2017 WCHRI Clinical Research Seed Grant (University of Alberta), “Toward novel diagnostic solutions for children with celiac disease, using common genetic variation”. I designed analysis strategy and study plan and have brought the Genomics collaboration with the University of Exeter to The University of Alberta. Co-I (with 3 others, PI Justine Turner, 1 hour per week)  

1. 2015-2016 MRC Proximity to Discover University of Exeter, “bringing new genotyping and sequencing technologies to the clinic”. I have led the study design and analysis strategy for this project and was first author on the first paper from our group with a second paper submitted for publication. Co-PI (with 2 others)