World class research today, superior patient care tomorrow

World class research today, superior patient care tomorrow

Academic excellence

As recognized leaders in pharmacogenomics (PGx), Dr. Broeckel and the RPRD research team are known for their scientific rigor and academic excellence. We partner with the world’s leading medical institutions to advance PGx research and practice.

View our academic publications and scientific contributions listed below that highlight our academic excellence and commitments in scientific and clinical research.

Dr Broeckel Pharmacogenomics Researcher

Publications:

Charity, N. et al. PharmVar GeneReview: CYP2D6. Clin Pharmacol Ther. 2019 Sep [ePub ahead].

Hoshtsuki, K. et al. Challenges in Clinical Implementation of CYP2D6 Genotyping: Choice of Variants to Test Affects Phenotype Determination. Genetics in Medicine. 2020. 22 (1): 232.

Gaedigk, A. et al. Characterization of Reference Materials for Genetic Testing of CYP2D6 Alleles A GeT-RM Collaborative Project. The Journal of Molecular Diagnostics. 2019. 21 (6): P1034.

Yang JJ, et al. Pharmacogene Variation Consortium Gene Introduction: NUDT15. Clin Pharmacol Ther. 2019 May;105(5):1091-1094.

Bhatt DK, et al. Age- and Genotype-Dependent Variability in the Protein Abundance and Activity of Six Major Uridine Diphosphate-Glucuronosyltransferases in Human Liver. Clin Pharmacol Ther. 2019 Jan;105(1):131-41.

Bhatt DK, et al. Hepatic Abundance and Activity of Androgen and Drug Metabolizing Enzyme, UGT2B17, are Associated with Genotype, Age, and Sex. Drug Metab Dispos. 2018 Jun;46(6):888-96.

Pasternak AL, et al. The Impact of the UGT1A1*60 Allele on Bilirubin Serum Concentrations. Pharmacogenomics. 2017 Jan;18(1):5-16.

Gammal RS, et al. Pharmacogenetics for Safe Codeine Use in Sickle Cell Disease. Pediatrics. 2016 Jul;138(1).

Yang W, et al. Comparison of Genome Sequencing and Clinical Genotyping for Pharmacogenes. Clin Pharmacol Ther. 2016 Oct;100(4):380-8.

Pratt VM, et al. Characterization of 137 Genomic DNA Reference Materials for 28 Pharmacogenetic Genes: A GeT-RM Collaborative Project. J Mol Diagn. 2016 Jan;18(1):109-23.

Dunnenberger HM, et al. Preemptive Clinical Pharmacogenetics Implementation: Current Programs in Five US Medical Centers. Annu Rev Pharmacol Toxicol. 2015 Jan;55:89-106.

Thompson P, et al. Pharmacokinetics and Pharmacogenomics of Daunorubicin in Children: a Report From the Children’s Oncology Group. Cancer Chemother Pharmacol. 2014 Oct;74(4):831-8.

Hicks JK, et al. Voriconazole Plasma Concentrations in Immunocompromised Pediatric Patients Vary by CYP2C19 Diplotypes. Pharmacogenomics. 2014 Jun;15(8):1065-78.

Miller AW, et al. Development of Reusable Logic for Determination of Statin Exposure-time from Electronic Health Records. J Biomed Inform. 2014 Jun;49:206-12.

Hoffman JM, et al. PG4KDS: a Model for the Clinical Implementation of Pre-emptive Pharmacogenetics. Am J Med Genet C Semin Med Genet. 2014 Mar;166C(1):45-55.

Bell GC, et al. Development and Use of Active Clinical Decision Support for Preemptive Pharmacogenomics. J Am Med Inform Assoc. 2014 Feb;21(e1):e93-9.

Shuldiner AR, et al. The Pharmacogenomics Research Network Translational Pharmacogenetics Program: Overcoming Challenges of Real-world Implementation. Clin Pharmacol Ther. 2013 Aug;94(2):207-10.

Hicks JK, et al. A Clinician-Driven Automated System for Integration of Pharmacogenetic Interpretations into an Electric Medical Record. Clin Pharmacol Ther. 2012 Nov;92(5):563-6.

Fernandez CA, et al. Concordance of DMET Plus Genotyping Results With Those of Orthogonal Genotyping Methods. Clin Pharmacol Ther. 2012 Sep;92(3):360-5. 

Click here for selected publications utilizing Next Generation Sequencing.

Upcoming Conference Abstract

Performance Analysis of a Comprehensive Clinically Focused Pharmacogenetic Assay

Pharmacogenomics Research Network (PGRN) Meeting 2020

INTRODUCTION: Genotyping of relevant pharmacogenetic (PGx) genes and HLA typing for known  associations with drug metabolism and hypersensitivity allows for personalized drug selection and dosing prior to administration. The accuracy and reproducibility of testing methodologies are critical to ensure accurate phenotype assignment. We have previously demonstrated the quality and relevance of the PharmacoScan™ (pScan) assay for clinical PGx testing. While pScan offers the most comprehensive genotyping platform (4,627 ADME markers in 1,191 genes + copy number analysis) there continues to be a need for a more targeted, higher throughput and more cost-effective platforms. In this study we tested the PharmacoFocus™ (pFocus) assay, a targeted assay (2,000+ ADME markers in 150 genes + copy number analysis) that includes highly relevant PGx genes and markers and offers the potential for routine and reliable clinical PGx testing.

METHODS: Genomic DNA (gDNA) was acquired from Coriell (isolated from LCL cell lines) or isolated from Liver, blood, buccal and saliva. Samples were batched (including mixed sample types per plate) and run using the PharmacoScan™ Assay Kit (pScan), 24-Format or the PharmacoFocusTM Assay Kit (pFocus), 96-Format. Array analysis was done using the Axiom™ Analysis Suite and performance of each assay was determined by calculating both inter- and intra-run specificity, sensitivity, and concordance.

RESULTS: There are 8,416 probes that are used for genotyping on the pFocus assay. To test the quality of probes, the per sample genotypes were compared for all the probes. 99.6% of the probes showed high inter-run concordance. On a sample level, all samples genotyped on pFocus showed a passing QC call rate >98%. The intra- and inter-run concordance for all the samples run on pFocus was >99%. The intra-run concordance metrics include samples from different gDNA sources. When comparing the pScan and pFocus assays, >8,000 genotyping probes were used. On the probe level, all samples demonstrated >99.5% concordance between the two assays. The star allele haplotype concordance was >99.3% for the relevant PGx genes. All samples on both assays showed 100% concordance with copy number qPCR results for CYP2D6, including CYP2D6/CYP2D7 hybrids.

CONCLUSIONS: We evaluated the pFocus assay, a more targeted array-based platform derived from pScan. PharmacoFocus, includes the most clinically relevant and actionable PGx genes and markers. The intra- and inter-run results demonstrate that despite the reduced content on pFocus, the quality of the genotypes is highly accurate and reproducible. We also show that the assay performs well for gDNA samples derived from different source types. The more targeted scope of pFocus makes it a high throughput and cost-effective clinical testing platform to complement the strength of the pScan assay, which lies in a broader scope of clinical, research and in certain cases discovery-based testing.

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Conference abstracts:

Pharmacogenomic Genotyping Performance Across Biological Specimens

Presented at the University of Minnesota Biennial Pharmacogenomics Conference 2020

Turner, A., Aggarwal, P., Scharer, G., Derezenski, A., Gaedigk, A., Broeckel, U.

Click here to download the poster

Characterization of CYP2D6 Structural Variants Containing the CYP2D6 *68 Hybrid

Turner, A, Nofziger, C, Boone, E, Scantamburlo, G, Vanoni, S, Haidar, C, Relling, M, Broeckel, U, Gaedigk, A.

Presented at the American Society of Human Genetics (ASHG) annual conference 2019  

Click here to download poster

 

Identification of Novel CYP2D6 Haplotypes that Interfere with TaqMan Copy Number Analysis

Turner A, Aggarwal, P, Boone E, Haidar, C, Relling, M, Broeckel, U, Gaedigk, A.

Presented at the Clinical Pharmacogenetics Implementation Consortium (CPIC) meeting 2019

Click here to download poster

The PharmacoScanTM Array: Performance Across Biological Specimens

Turner, A, Aggarwal, P, Lorier, R, Gaedigk, A, Broeckel, U

Presented at the Clinical Pharmacogenetics Implementation Consortium (CPIC) meeting 2019

Click here to download poster

TPMT and NUDT15 Genotyping for Comprehensive Detection of Thiopurine Sensitivity in Multi-Ethnic Populations

Turner, A, Aggarwal, P, Lorier, R, Scharer, G, Broeckel, U.

Presented at the Clinical Pharmacogenetics Implementation Consortium (CPIC) meeting 2019

Click here to download poster

Four Novel NUDT15 Haplotypes Relevant for Treatment of Acute Lymphoblastic Leukemia

Turner A, Aggarwal P, Scharer G, Broeckel U.

Presented at The American Society of Pediatric Hematology/Oncology (ASPHO) 2019.

Click here to download poster.

Identification of Novel CYP2D6 Haplotypes that Interfere with TaqMan Copy Number Analysis

Turner A, Aggarwal P, Boone EC, Haidar CE, Relling M., Broeckel U, Gaedig, A.

Presented at American Society of Human Genetics (ASHG) 2018. 

Click here to download poster.

Implementation of Affymetrix PharmacoScanTM for Comprehensive Preemptive Clinical Pharmacogenetic Testing

Turner A, Lorier R, Aggarwal, P Matter A, Broeckel U.

Presented at American Society of Human Genetics (ASHG) 2016. 

Click here to download poster.

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Our additional contributions to PGx development

Clinical Pharmacogenetics Implementation Consortium (CPIC):

Drs. Broeckel (CEO and founder) and Scharer (CMO) are both long-standing members of the CPIC® since its inception in 2009.  CPIC is a pioneering PGx consortium committed to facilitating the implementation of PGx testing in the clinic by providing actionable clinical guidelines to translate genetic tests results into customized patient-focused prescribing decisions by physicians for certain drugs. The detailed evidence-based, gene/drug clinical recommendations created by CPIC are peer-reviewed and are being increasingly used in the clinical practice. They are regarded as the standard guideline in PGx clinical implementation.

Read more about CPIC.

PharmVar

Amy Turner (Director of Research and Development) is a member of the Pharmacogene Variation (PharmVar) Consortium and serves as a gene expert for CYP2D6, NUDT15, and DPYD.

PharmVar was established in 2018 and funded by the Pharmacogenomics Research Network (PGRN) to serve as repository for PGx gene data and its nomenclature. PharmVar aims to facilitate and develop a standardized PGx gene nomenclature for the entire global PGx community.

Amy Turner’s contribution to the PharmVar NUDT15 gene introduction:

Yang JJ, et al. Pharmacogene Variation Consortium Gene Introduction: NUDT15. Clin Pharmacol Ther. 2018 Dec 4. doi: 10.1002/cpt.1268.

Amy Turner’s contribution to the PharmVar Gene Review CYP2D6

Charity, N. et al. PharmVar GeneReview: CYP2D6. Clin Pharmacol Ther. 2019 Sep [ePub ahead].

Read more about PharmVar.

Genetic Testing Reference Materials Coordination Program (GeT-RM)

Dr. Broeckel and his research team have been an important contributor to the GeT-RM since 2015. As part of the Clinical Laboratory Improvement Amendments (CLIA) regulations of 1988, the Get-RM program is supported by the Centers for Disease Control and Prevention (CDC). The goal of the GeT-RM is to establish a PGx community dedicated to creating reference materials, quality control measures, and proficiency testing for genetic testing.

Dr. Broeckel’s team has characterized the PGx impact of genomic DNA reference materials utilizing the PharmacoScanTM and its predecessor DMET platform.

Pratt VM, et al. Characterization of 137 Genomic DNA Reference Materials for 28 Pharmacogenetic Genes: A GeT-RM Collaborative Project. J Mol Diagn. 2016 Jan;18(1):109-23.PMID: 26621101 PMCID: 4695224.

Gaedigk, A. et al. Characterization of Reference Materials for Genetic Testing of CYP2D6 Alleles A GeT-RM Collaborative Project. The Journal of Molecular Diagnostics. 2019 Aug [ePub ahead].

Read more about Get-RM program.

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Collaborating Opportunities

As a team primarily driven by passion for science, we are excited to work with the bright minds in the precision medicine community. If you are interested in collaborating with RPRD, please contact us to discuss potential opportunities.

Improve Drug R&D

Pharmacogenetics testing is an increasingly important tool to mitigate risks for clinical trials, interpretation of clinical data and retrospective studies.

Improve Patient Outcomes

Through our continued research in advanced PGx technologies and solutions, we help clinicians practice personalized medicine to achieve better outcomes for their patients.