About

Graeme Bell is the Kovler Family Distinguished Service Professor of Medicine at the University of Chicago, where he is also a member of the Committee on Genetics, Genomics and Systems Biology and the Committee on Molecular Metabolism and Nutrition. His research program focuses on the genetics of diabetes and other metabolic disorders, with particular emphasis on insulin mutations and diabetes. Dr. Bell has contributed to understanding the genetics underlying diabetes through extensive research, including exome sequencing of large cohorts and studies on insulin gene mutations. His work has provided insights into diagnosis and treatment, exemplified by over a decade of research through the University of Chicago Monogenic Diabetes Registry. He has been recognized with numerous awards, including the Banting Medal for Scientific Achievement from the American Diabetes Association, the Manpei Suzuki International Prize for Diabetes Research, and election to prestigious organizations such as the American Academy of Arts and Sciences, the National Academy of Medicine, and the American Association for the Advancement of Science.

Research topics

• Endocrinology
• Medicine
• Internal medicine
• Biology
• Bioinformatics
• Genetics
• Pediatrics
• Family medicine
• Computational biology

Selected publications

• Microcephaly, epilepsy, and neonatal diabetes due to compound heterozygous mutations in IER3IP1: Insights into the natural history of a rare disorder

  UNC Libraries · 2024-03-19 · 4 citations

  articleOpen access

  Neonatal diabetes mellitus is known to have over 20 different monogenic causes. A syndrome of permanent neonatal diabetes along with primary microcephaly with simplified gyral pattern associated with severe infantile epileptic encephalopathy was recently described in two independent reports in which disease-causing homozygous mutations were identified in the immediate early response-3 interacting protein-1 (IER3IP1) gene. We report here an affected male born to a non-consanguineous couple who was noted to have insulin-requiring permanent neonatal diabetes, microcephaly, and generalized seizures. He was also found to have cortical blindness, severe developmental delay and numerous dysmorphic features. He experienced a slow improvement but not abrogation of seizure frequency and severity on numerous anti-epileptic agents. His clinical course was further complicated by recurrent respiratory tract infections and he died at 8years of age. Whole exome sequencing was performed on DNA from the proband and parents. He was found to be a compound heterozygote with two different mutations in IER3IP1: p.Val21Gly (V21G) and a novel frameshift mutation p.Phe27fsSer*25. IER3IP1 is a highly conserved protein with marked expression in the cerebral cortex and in beta cells. This is the first reported case of compound heterozygous mutations within IER3IP1 resulting in neonatal diabetes. The triad of microcephaly, generalized seizures, and permanent neonatal diabetes should prompt screening for mutations in IER3IP1. As mutations in genes such as NEUROD1 and PTF1A could cause a similar phenotype, next-generation sequencing approaches-such as exome sequencing reported here-may be an efficient means of uncovering a diagnosis in future cases.

  PublisherDOI

• Implementing genetic testing in diabetes: Knowledge, perceptions of healthcare professionals, and barriers in a developing country

  Population Medicine · 2024-03-15 · 1 citations

  articleOpen access

  INTRODUCTION: Maturity-Onset Diabetes of the Young (MODY) is an unusual type of diabetes often missed in clinical practice, especially in Africa. Treatment decisions for MODY depend on a precise diagnosis, only made by genetic testing. We aimed to determine MODY knowledge among Nigerian healthcare professionals (HCPs), their perceptions, and barriers to the implementation of genetic testing in diabetes patients. METHODS: A cross-sectional survey was conducted among doctors and nurses in three levels of public and private healthcare institutions in Ibadan, Nigeria, from December 2018 to June 2019. In all, 70% and 30% of a total 415 participants were recruited from public and private centers, respectively. HCPs were recruited in a 60:40% ratio, respectively. A 51-item instrument was used to assess MODY knowledge, perceptions of HCPs, and barriers to the implementation of genetic testing in diabetes patients. RESULTS: In the survey, 43.4% self-rated their current MODY knowledge to be at least moderate. About 68%, 73% and 86%, respectively, correctly answered 3 of 5 questions on basic genetics' knowledge. However, only 1 of 7 MODY-specific questions was answered correctly by 72.7% of the respondents. The mean basic genetics and MODY-specific knowledge scores were 2.6/5 (SD=1.0) and 1.8/9 (SD=1.3), respectively. Multiple linear regression showed higher mean scores among those aged 30-49 years, those with degrees and fellowships (except PhD), and general practitioners; 360 (80.0%) perceived that genetic testing plays a central role in diabetes care. Barriers to genetic testing were lack of access to testing facilities, guidance on the use of and updates/educational materials on genetic testing (82.7%, 62.1% and 50.3%, respectively). CONCLUSIONS: The level of MODY awareness and knowledge among Nigerian HCPs is unacceptably low with a lack of access to genetic testing facilities. These can hinder the implementation of precision diabetes medicine. Increased awareness, provision of decision support aids, and genetic testing facilities are urgently needed.

  PublisherOA PDFDOI

• Functionally oriented analysis of cardiometabolic traits in a trans-ethnic sample

  UNC Libraries · 2024-03-19

  articleOpen accessSenior author

  Interpretation of genetic association results is difficult because signals often lack biological context. To generate hypotheses of the functional genetic etiology of complex cardiometabolic traits, we estimated the genetically determined component of gene expression from common variants using PrediXcan (1) and determined genes with differential predicted expression by trait. PrediXcan imputes tissue-specific expression levels from genetic variation using variant-level effect on gene expression in transcriptome data. To explore the value of imputed genetically regulated gene expression (GReX) models across different ancestral populations, we evaluated imputed expression levels for predictive accuracy genome-wide in RNA sequence data in samples drawn from European-Ancestry and African-Ancestry populations and identified substantial predictive power using European-derived models in a non-European target population.We then tested the association of GReX on 15 cardiometabolic traits including blood lipid levels, body mass index, height, blood pressure, fasting glucose and insulin, RR interval, fibrinogen level, factor VII level and white blood cell and platelet counts in 15 755 individuals across three ancestry groups, resulting in 20 novel gene-phenotype associations reaching experiment-wide significance across ancestries. In addition, we identified 18 significant novel gene-phenotype associations in our ancestry-specific analyses. Top associations were assessed for additional support via query of S-PrediXcan (2) results derived from publicly available genome-wide association studies summary data. Collectively, these findings illustrate the utility of transcriptome-based imputation models for discovery of cardiometabolic effect genes in a diverse dataset.

  PublisherDOI

• The Rare and Atypical Diabetes Network (RADIANT) Study: Design and Early Results

  Diabetes Care · 2023 · 15 citations

  • Medicine
  • Genetics
  • Bioinformatics

  OBJECTIVE: The Rare and Atypical Diabetes Network (RADIANT) will perform a study of individuals and, if deemed informative, a study of their family members with uncharacterized forms of diabetes. RESEARCH DESIGN AND METHODS: The protocol includes genomic (whole-genome [WGS], RNA, and mitochondrial sequencing), phenotypic (vital signs, biometric measurements, questionnaires, and photography), metabolomics, and metabolic assessments. RESULTS: Among 122 with WGS results of 878 enrolled individuals, a likely pathogenic variant in a known diabetes monogenic gene was found in 3 (2.5%), and six new monogenic variants have been identified in the SMAD5, PTPMT1, INS, NFKB1, IGF1R, and PAX6 genes. Frequent phenotypic clusters are lean type 2 diabetes, autoantibody-negative and insulin-deficient diabetes, lipodystrophic diabetes, and new forms of possible monogenic or oligogenic diabetes. CONCLUSIONS: The analyses will lead to improved means of atypical diabetes identification. Genetic sequencing can identify new variants, and metabolomics and transcriptomics analysis can identify novel mechanisms and biomarkers for atypical disease.

  PublisherOA PDFDOI

• Susumu Seino, MD, DMSci (1948–2021): A Pioneer in the Biology of Insulin Secretion

  Diabetes · 2022-11-21

  articleOpen accessCorresponding
  PublisherOA PDFDOI

• In celebration of a century with insulin – Update of insulin gene mutations in diabetes

  Molecular Metabolism · 2021 · 51 citations

  • Genetics
  • Medicine
  • Biology

  BACKGROUND: While insulin has been central to the pathophysiology and treatment of patients with diabetes for the last 100 years, it has only been since 2007 that genetic variation in the INS gene has been recognised as a major cause of monogenic diabetes. Both dominant and recessive mutations in the INS gene are now recognised as important causes of neonatal diabetes and offer important insights into both the structure and function of insulin. It is also recognised that in rare cases, mutations in the INS gene can be found in patients with diabetes diagnosed outside the first year of life. SCOPE OF REVIEW: This review examines the genetics and clinical features of monogenic diabetes resulting from INS gene mutations from the first description in 2007 and includes information from 389 patients from 292 families diagnosed in Exeter with INS gene mutations. We discuss the implications for diagnosing and treating this subtype of monogenic diabetes. MAJOR CONCLUSIONS: The dominant mutations in the INS gene typically affect the secondary structure of the insulin protein, usually by disrupting the 3 disulfide bonds in mature insulin. The resulting misfolded protein results in ER stress and beta-cell destruction. In contrast, recessive INS gene mutations typically result in no functional protein being produced due to reduced insulin biosynthesis or loss-of-function mutations in the insulin protein. There are clinical differences between the two genetic aetiologies, between the specific mutations, and within patients with identical mutations.

  PublisherDOI

• Insight on Diagnosis and Treatment From Over a Decade of Research Through the University of Chicago Monogenic Diabetes Registry

  Frontiers in Clinical Diabetes and Healthcare · 2021 · 18 citations

  • Medicine
  • Family medicine
  • Pediatrics

  (16%). Over the last decade, improvements in data collection for the University of Chicago Monogenic Diabetes Registry have resulted in increased knowledge of the natural history of monogenic diabetes, as well as a better understanding of the most effective treatments. The University of Chicago Monogenic Diabetes Registry serves as a valuable resource that will continue to provide evidence to support improved clinical care and patient outcomes in monogenic diabetes.

  PublisherOA PDFDOI

• Dyslipidemia : Classification, Screening

  2021-01-01

  article1st authorCorresponding

  Dyslipidemia is an abnormal amount of lipids (e.g., triglycerides, cholesterol and/or fat phospholipids) within the blood. Dyslipidemia may be a risk factor for the event of atherosclerotic disorder (ASCVD). ASCVD includes arteriacoronaria disease, cerbrovascular disease, and peripheral artery disease. Although dyslipidemia may be a risk factor for ASCVD, abnormal levels don’t suggest that lipid lowering agents got to be started. Other factors, like comorbid conditions and lifestyle additionally to dyslipidemia, is taken into account during a cardiovascular risk assessment. In developed countries, most dyslipidemias are hyperlipidemias; that’s , an elevation of lipids within the blood. this is often often thanks to diet and lifestyle. Prolonged elevation of insulin resistance also can cause dyslipidemia. Likewise, increased levels of O-GlcNAc transferase (OGT) may cause dyslipidemia.

  Publisher

• Building an integrated model that spans all aspects of ecosystem services

  Duo Research Archive (University of Oslo) · 2020-03-01

  articleOpen access1st authorCorresponding

  Denne rapporten beskriver utviklingen av en ny metode og en digital kartløsning for å visualisere ulike økosystemtjenester på nasjonal skala i Norge.

  Publisher

• Transancestral fine-mapping of four type 2 diabetes susceptibility loci highlights potential causal regulatory mechanisms

  UNC Libraries · 2020-04-18 · 1 citations

  articleOpen access

  To gain insight into potential regulatory mechanisms through which the effects of variants at four established type 2 diabetes (T2D) susceptibility loci (CDKAL1, CDKN2A-B, IGF2BP2 and KCNQ1) are mediated, we undertook transancestral fine-mapping in 22 086 cases and 42 539 controls of East Asian, European, South Asian, African American and Mexican American descent. Through high-density imputation and conditional analyses, we identified seven distinct association signals at these four loci, each with allelic effects on T2D susceptibility that were homogenous across ancestry groups. By leveraging differences in the structure of linkage disequilibrium between diverse populations, and increased sample size, we localised the variants most likely to drive each distinct association signal. We demonstrated that integration of these genetic fine-mapping data with genomic annotation can highlight potential causal regulatory elements in T2D-relevant tissues. These analyses provide insight into the mechanisms through which T2D association signals are mediated, and suggest future routes to understanding the biology of specific disease susceptibility loci.

  PublisherDOI

Recent grants

• Genetics and Genomics Core

  NIH · $38.6M · 1996–2028

• Integrated Clinical and Basic Endocrinology Research

  NIH · $8.1M · 1975–2026

• NIH Grant P01DK044840

  NIH · $4.8M · 2003

• NIH Grant R01DK047486

  NIH · $3.0M · 2006

• NIH Grant P60DK020595

  NIH · $60.7M · 2013

Frequent coauthors

• Nancy J. Cox

  227 shared

• Jun Takeda

  Juntendo University

  164 shared

• Markus Stoffel

  ETH Zurich

  135 shared

• James Scott

  113 shared

• Kazuya Yamagata

  Kumamoto University

  108 shared

• Susumu Seino

  Kobe University

  106 shared

• Donald F. Steiner

  University of Chicago

  104 shared

• Susan Colilla

  Teva Pharmaceuticals (Australia)

  101 shared

Labs

• Graeme Bell LabPI

Education

• Ph.D., Biochemistry

  University of California San Francisco

  1977

• M.S., Biology

  University of Calgary

  1971

• B.S., Zoology

  University of Calgary

  1968

Awards & honors

• The Banting Medal for Scientific Achievement of the American…
• Manpei Suzuki International Prize for Diabetes Research (201…
• Fellow of the American Association of the Advancement of Sci…
• American Academy of Arts and Sciences (2008)
• National Academy of Medicine (1998)