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Dr Graham Heap

Academic Clinical Fellow and Honorary Clinical Research Fellow

01392 406852

RILD Building L3/06C

I work as an academic physician at the Royal Devon and Exeter NHS Trust and the University of Exeter. My primary research interest lies in multi-centre pharmacogenomic studies. These studies aim to characterise the clinical and genetic factors that predispose patients to the development of drug side effects and responses to medication. I am a co-investigator for six gastroenterology pharmacogenetic studies that investigate drug side effects (PRED6) and a co-investigator for the PANTS study, a large prospective observation trial investigating the response to anti-TNF agents in Crohn's disease in over 1000 patients. I lead the data analysis team for both studies. I am particularly interested in translating the results of these studies into clinical practice. I have experience working in diverse matrix teams in both a clinical and academic environment and have extensive experience interacting with the pharmaceutical industry as an investigator for both industry and investigator sponsored trials.

Qualifications

2015 - MRCP

2012 - MBBS Medicine

2009 - PhD Gastroenterology

2006 - BSc (Hons) Basic Medical Sciences with Physiology 

Links

Research

Research projects

Predicting Serious Drug Side Effects In Gastroenterology (PRED4) is a group of studies that aim to build up cohorts of pateints from around the world who have developed serious adverse reactions to drugs commonly used in gastroenterology. Once a cohort of pateints has been establiesh and a rigorous causality assessment has been undertaken, detailed genetic association tests are under taken with both exome sequencing and genome wide association study methodologies are undertaken. The identification of genetic associations with adverse drug side effects will enable targeted therapy for at risk pateints and novel insights into adverse drug reactions to aid furture molecule development. The adverse drug reactions currently under study include:

Personalised anti-TNF therapy in Crohn’s disease (PANTS) is a 3 year prospective uncontrolled cohort study investigating primary non-response (PNR), loss of response (LOR) and adverse drug reactions (ADRs) to Infliximab (IFX) and Adalimumab (ADA) in patients with severe active luminal Crohn’s disease. The primary objective of this study is to investigate the mechanisms that underlie PNR, LOR and ADRs. The secondary aims are to develop personalised anti-TNF treatment strategies, through the identification of clinically meaningful serological and genetic predictive markers.

This study builds on the achievements of the UK and international IBDGC in identifying IBD susceptibility genes. These discoveries have provided important insights into disease pathogenesis but are not expected to have an impact in the clinic for a number of years. This study aims to take genetics and biomarker discovery into the IBD clinic to address questions of immediate clinical importance.

The study utilises the network of 120 UK hospitals currently participating in the UK IBDGC pharmacogenetic programme (www.ibdresearch.co.uk) which includes PRED4, a pharmacogenetic study of serious drug side effects. The collection of clinical data is aligned with the data being collected by the Royal College of Physicians UK IBD Biologics Audit. In order to avoid duplicate data entry we will share relevant anonymised data with the UK IBD Biologics Audit (and in due course with the UK IBD registry). This study has been adopted by the UK NIHR CRN and patient recruitment, and data entry will be supported by CLRN nurses

Patients, starting anti-TNF therapy for the first time will be invited to participate by their gastroenterologist. Routine research visits are scheduled for weeks 0, 12, 14, 30 and 54, and additional visits scheduled if LOR occurs or the drug is stopped. For patients receiving IFX additional short visits are scheduled prior to infusions at week 2, 6, 22, 38, 46. To minimise inconvenience to patients all visits will be scheduled to coincide with routine outpatient or infusion clinic appointments.

This observational study is funded by CORE, the British Society of Gastroenterology research charity and by unrestricted educational grants from Merck Sharp & Dohme (MSD) and AbbVie. The sponsor of the study is the Royal Devon and Exeter NHS Foundation Trust.

Key publications | Publications by category | Publications by year

Key publications


Ben-Horin S, Heap GA, Ahmad T, Kim H, Kwon T, Chowers Y (2015). The immunogenicity of biosimilar infliximab: can we extrapolate the data across indications?. Expert Rev Gastroenterol Hepatol, 9 Suppl 1, 27-34. Abstract.  Author URL.
Heap GA, Weedon MN, Bewshea CM, Singh A, Chen M, Satchwell JB, Vivian JP, So K, Dubois PC, Andrews JM, et al (2014). HLA-DQA1-HLA-DRB1 variants confer susceptibility to pancreatitis induced by thiopurine immunosuppressants. Nat Genet, 46(10), 1131-1134. Abstract.  Author URL.
Heap GA, Yang JHM, Downes K, Healy BC, Hunt KA, Bockett N, Franke L, Dubois PC, Mein CA, Dobson RJ, et al (2010). Genome-wide analysis of allelic expression imbalance in human primary cells by high-throughput transcriptome resequencing. Hum Mol Genet, 19(1), 122-134. Abstract.  Author URL.
Heap GA, Trynka G, Jansen RC, Bruinenberg M, Swertz MA, Dinesen LC, Hunt KA, Wijmenga C, Vanheel DA, Franke L, et al (2009). Complex nature of SNP genotype effects on gene expression in primary human leucocytes. BMC Med Genomics, 2 Abstract.  Author URL.  Full text.
Heap GA, van Heel DA (2009). Genetics and pathogenesis of coeliac disease. Semin Immunol, 21(6), 346-354. Abstract.  Author URL.
Heap GA, van Heel DA (2009). The genetics of chronic inflammatory diseases. Hum Mol Genet, 18(R1), R101-R106. Abstract.  Author URL.

Publications by category


Journal articles

Ben-Horin S, Heap GA, Ahmad T, Kim H, Kwon T, Chowers Y (2015). The immunogenicity of biosimilar infliximab: can we extrapolate the data across indications?. Expert Rev Gastroenterol Hepatol, 9 Suppl 1, 27-34. Abstract.  Author URL.
Heap GA, Weedon MN, Bewshea CM, Singh A, Chen M, Satchwell JB, Vivian JP, So K, Dubois PC, Andrews JM, et al (2014). HLA-DQA1-HLA-DRB1 variants confer susceptibility to pancreatitis induced by thiopurine immunosuppressants. Nat Genet, 46(10), 1131-1134. Abstract.  Author URL.
Hunt KA, Smyth DJ, Balschun T, Ban M, Mistry V, Ahmad T, Anand V, Barrett JC, Bhaw-Rosun L, Bockett NA, et al (2012). Rare and functional SIAE variants are not associated with autoimmune disease risk in up to 66,924 individuals of European ancestry. NATURE GENETICS, 44(1), 3-5. Author URL.
Nanty L, Carbajosa G, Heap GA, Ratnieks F, van Heel DA, Down TA, Rakyan VK (2011). Comparative methylomics reveals gene-body H3K36me3 in Drosophila predicts DNA methylation and CpG landscapes in other invertebrates. Genome Res, 21(11), 1841-1850. Abstract.  Author URL.
Trynka G, Hunt KA, Bockett NA, Romanos J, Mistry V, Szperl A, Bakker SF, Bardella MT, Bhaw-Rosun L, Castillejo G, et al (2011). Dense genotyping identifies and localizes multiple common and rare variant association signals in celiac disease. Nat Genet, 43(12), 1193-1201. Abstract.  Author URL.
Heap GA, Yang JHM, Downes K, Healy BC, Hunt KA, Bockett N, Franke L, Dubois PC, Mein CA, Dobson RJ, et al (2010). Genome-wide analysis of allelic expression imbalance in human primary cells by high-throughput transcriptome resequencing. Hum Mol Genet, 19(1), 122-134. Abstract.  Author URL.
Dubois PCA, Trynka G, Franke L, Hunt KA, Romanos J, Curtotti A, Zhernakova A, Heap GAR, Adány R, Aromaa A, et al (2010). Multiple common variants for celiac disease influencing immune gene expression. Nat Genet, 42(4), 295-302. Abstract.  Author URL.
Koskinen LLE, Einarsdottir E, Dukes E, Heap GAR, Dubois P, Korponay-Szabo IR, Kaukinen K, Kurppa K, Ziberna F, Vatta S, et al (2009). Association study of the IL18RAP locus in three European populations with coeliac disease. Hum Mol Genet, 18(6), 1148-1155. Abstract.  Author URL.
Trynka G, Zhernakova A, Romanos J, Franke L, Hunt KA, Turner G, Bruinenberg M, Heap GA, Platteel M, Ryan AW, et al (2009). Coeliac disease-associated risk variants in TNFAIP3 and REL implicate altered NF-kappaB signalling. Gut, 58(8), 1078-1083. Abstract.  Author URL.
Heap GA, Trynka G, Jansen RC, Bruinenberg M, Swertz MA, Dinesen LC, Hunt KA, Wijmenga C, Vanheel DA, Franke L, et al (2009). Complex nature of SNP genotype effects on gene expression in primary human leucocytes. BMC Med Genomics, 2 Abstract.  Author URL.  Full text.
Heap GA, van Heel DA (2009). Genetics and pathogenesis of coeliac disease. Semin Immunol, 21(6), 346-354. Abstract.  Author URL.
Heap GA, van Heel DA (2009). The genetics of chronic inflammatory diseases. Hum Mol Genet, 18(R1), R101-R106. Abstract.  Author URL.
Hunt KA, Zhernakova A, Turner G, Heap GAR, Franke L, Bruinenberg M, Romanos J, Dinesen LC, Ryan AW, Panesar D, et al (2008). Newly identified genetic risk variants for celiac disease related to the immune response. Nat Genet, 40(4), 395-402. Abstract.  Author URL.
Smyth DJ, Plagnol V, Walker NM, Cooper JD, Downes K, Yang JHM, Howson JMM, Stevens H, McManus R, Wijmenga C, et al (2008). Shared and distinct genetic variants in type 1 diabetes and celiac disease. N Engl J Med, 359(26), 2767-2777. Abstract.  Author URL.

Conferences

Heap GA, Singh A, Bewshea C, Weedon MN, Cole A, Creed T, Greig E, Irving P, Lindsay J, Mawdsley J, et al (2014). THIOPURINE INDUCED PANCREATITIS IN INFLAMMATORY BOWEL DISEASE: CLINICAL FEATURES AND GENETIC DETERMINANTS.  Author URL.
So K, Bewshea C, Heap GA, Muller AF, Daneshmend TK, Hart AL, Orchard TR, Irving PM, Russell RK, Wilson DC, et al (2013). 5-AMINOSALICYLATE (5-ASA) INDUCED NEPHROTOXICITY IN INFLAMMATORY BOWEL DISEASE.  Author URL.

Publications by year


2015

Ben-Horin S, Heap GA, Ahmad T, Kim H, Kwon T, Chowers Y (2015). The immunogenicity of biosimilar infliximab: can we extrapolate the data across indications?. Expert Rev Gastroenterol Hepatol, 9 Suppl 1, 27-34. Abstract.  Author URL.

2014

Heap GA, Weedon MN, Bewshea CM, Singh A, Chen M, Satchwell JB, Vivian JP, So K, Dubois PC, Andrews JM, et al (2014). HLA-DQA1-HLA-DRB1 variants confer susceptibility to pancreatitis induced by thiopurine immunosuppressants. Nat Genet, 46(10), 1131-1134. Abstract.  Author URL.
Heap GA, Singh A, Bewshea C, Weedon MN, Cole A, Creed T, Greig E, Irving P, Lindsay J, Mawdsley J, et al (2014). THIOPURINE INDUCED PANCREATITIS IN INFLAMMATORY BOWEL DISEASE: CLINICAL FEATURES AND GENETIC DETERMINANTS.  Author URL.

2013

So K, Bewshea C, Heap GA, Muller AF, Daneshmend TK, Hart AL, Orchard TR, Irving PM, Russell RK, Wilson DC, et al (2013). 5-AMINOSALICYLATE (5-ASA) INDUCED NEPHROTOXICITY IN INFLAMMATORY BOWEL DISEASE.  Author URL.

2012

Hunt KA, Smyth DJ, Balschun T, Ban M, Mistry V, Ahmad T, Anand V, Barrett JC, Bhaw-Rosun L, Bockett NA, et al (2012). Rare and functional SIAE variants are not associated with autoimmune disease risk in up to 66,924 individuals of European ancestry. NATURE GENETICS, 44(1), 3-5. Author URL.

2011

Nanty L, Carbajosa G, Heap GA, Ratnieks F, van Heel DA, Down TA, Rakyan VK (2011). Comparative methylomics reveals gene-body H3K36me3 in Drosophila predicts DNA methylation and CpG landscapes in other invertebrates. Genome Res, 21(11), 1841-1850. Abstract.  Author URL.
Trynka G, Hunt KA, Bockett NA, Romanos J, Mistry V, Szperl A, Bakker SF, Bardella MT, Bhaw-Rosun L, Castillejo G, et al (2011). Dense genotyping identifies and localizes multiple common and rare variant association signals in celiac disease. Nat Genet, 43(12), 1193-1201. Abstract.  Author URL.

2010

Heap GA, Yang JHM, Downes K, Healy BC, Hunt KA, Bockett N, Franke L, Dubois PC, Mein CA, Dobson RJ, et al (2010). Genome-wide analysis of allelic expression imbalance in human primary cells by high-throughput transcriptome resequencing. Hum Mol Genet, 19(1), 122-134. Abstract.  Author URL.
Dubois PCA, Trynka G, Franke L, Hunt KA, Romanos J, Curtotti A, Zhernakova A, Heap GAR, Adány R, Aromaa A, et al (2010). Multiple common variants for celiac disease influencing immune gene expression. Nat Genet, 42(4), 295-302. Abstract.  Author URL.

2009

Koskinen LLE, Einarsdottir E, Dukes E, Heap GAR, Dubois P, Korponay-Szabo IR, Kaukinen K, Kurppa K, Ziberna F, Vatta S, et al (2009). Association study of the IL18RAP locus in three European populations with coeliac disease. Hum Mol Genet, 18(6), 1148-1155. Abstract.  Author URL.
Trynka G, Zhernakova A, Romanos J, Franke L, Hunt KA, Turner G, Bruinenberg M, Heap GA, Platteel M, Ryan AW, et al (2009). Coeliac disease-associated risk variants in TNFAIP3 and REL implicate altered NF-kappaB signalling. Gut, 58(8), 1078-1083. Abstract.  Author URL.
Heap GA, Trynka G, Jansen RC, Bruinenberg M, Swertz MA, Dinesen LC, Hunt KA, Wijmenga C, Vanheel DA, Franke L, et al (2009). Complex nature of SNP genotype effects on gene expression in primary human leucocytes. BMC Med Genomics, 2 Abstract.  Author URL.  Full text.
Heap GA, van Heel DA (2009). Genetics and pathogenesis of coeliac disease. Semin Immunol, 21(6), 346-354. Abstract.  Author URL.
Heap GA, van Heel DA (2009). The genetics of chronic inflammatory diseases. Hum Mol Genet, 18(R1), R101-R106. Abstract.  Author URL.

2008

Hunt KA, Zhernakova A, Turner G, Heap GAR, Franke L, Bruinenberg M, Romanos J, Dinesen LC, Ryan AW, Panesar D, et al (2008). Newly identified genetic risk variants for celiac disease related to the immune response. Nat Genet, 40(4), 395-402. Abstract.  Author URL.
Smyth DJ, Plagnol V, Walker NM, Cooper JD, Downes K, Yang JHM, Howson JMM, Stevens H, McManus R, Wijmenga C, et al (2008). Shared and distinct genetic variants in type 1 diabetes and celiac disease. N Engl J Med, 359(26), 2767-2777. Abstract.  Author URL.

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