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Bristow Lab


The Bristow Laboratory investigates chronic heart failure, specifically the molecular mechanisms involved in the genesis and progression of pathologic hypertrophy and contractile dysfunction that are hallmarks of this disease.  We measure myocardial gene expression in human clinical studies, and we also work with animal and cell models to gain an understanding of how gene expression changes relate to phenotypic changes and/or differences.

Our studies correlating expression and phenotype have also allowed us to determine some of the genetic basis for the variability in therapeutic responses routinely observed for most classes of drugs, and these observations have been useful in the development of new pharmaceutical and device-based approaches to treat heart failure and other cardiovascular diseases. Over a more than 30 year period we have collected and processed diseased and control human heart samples from transplant and organ donor programs to create what is likely the largest tissue bank of its kind in the world. This tissue bank has proved extremely helpful in generating key hypotheses about important pathophysiological mechanisms, as well as in the discovery of genetic variants important in therapeutic responses.

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2019

GENETIC-AF: Bucindolol for the Maintenance of Sinus Rhythm in a Genotype-Defined Heart Failure Population.

Piccini JP, Abraham WT, Dufton C, Carroll IA, Healey JS, van Veldhuisen DJ, Sauer WH, Anand IS, White M, Wilton SB, Aleong R, Rienstra M, Krueger SK, Ayala-Paredes F, Khaykin Y, Merkely B, Miloradović V, Wranicz JK, Ilkhanoff L, Ziegler PD, Davis G, Emery LL, Marshall D, Kao DP, Bristow MR, Connolly SJ; Genotype-Directed Comparative Effectiveness Trial of Bucindolol and Toprol-XL for Prevention of Atrial Fibrillation/Atrial Flutter in Patients with Heart Failure Trial Investigators. JACC Heart Fail. 2019 Apr 29. pii: S2213-1779(19)30253-7. doi: 10.1016/j.jchf.2019.04.004. [Epub ahead of print]  PMID: 31042551

A PDE3A Promoter Polymorphism Regulates cAMP-Induced Transcriptional Activity in Failing Human Myocardium.

Sucharov CC, Nakano SJ, Slavov D, Schwisow JA, Rodriguez E, Nunley K, Medway A, Stafford N, Nelson P, McKinsey TA, Movsesian M, Minobe W, Carroll IA, Taylor MRG, Bristow MR. J Am Coll Cardiol. 2019 Mar 19;73(10):1173-1184. doi: 10.1016/j.jacc.2018.12.053.
PMID: 30871701

Impact of Degree of Left Ventricular Remodeling on Clinical Outcomes From Cardiac Resynchronization Therapy.

Shamoun F, De Marco T, DeMets D, Mei C, Lindenfeld J, Saxon LA, Boehmer JP, Leigh J, Yong P, Feldman AM, Bristow MR. JACC Heart Fail. 2019 Apr;7(4):281-290. doi: 10.1016/j.jchf.2018.11.004. Epub 2019 Feb 6.  PMID: 30738980

2018

Transcriptome analysis of human heart failure reveals dysregulated cell adhesion in dilated cardiomyopathy and activated immune pathways in ischemic heart failure.

Sweet ME, Cocciolo A, Slavov D, Jones KL, Sweet JR, Graw SL, Reece TB, Ambardekar AV, Bristow MR, Mestroni L, Taylor MRG. BMC Genomics. 2018 Nov 12;19(1):812. doi: 10.1186/s12864-018-5213-9.
PMID: 30419824

Dose Response of β-Blockers in Adrenergic Receptor Polymorphism Genotypes.

Parikh KS, Fiuzat M, Davis G, Neely M, Blain-Nelson P, Whellan DJ, Abraham WT, Adams KF Jr, Felker GM, Liggett SB, O'Connor CM, Bristow MR. Circ Genom Precis Med. 2018 Aug;11(8):e002210. doi: 10.1161/CIRCGEN.117.002210.
PMID: 30354340

Association of Variants in BAG3 With Cardiomyopathy Outcomes in African American Individuals.

Myers VD, Gerhard GS, McNamara DM, Tomar D, Madesh M, Kaniper S, Ramsey FV, Fisher SG, Ingersoll RG, Kasch-Semenza L, Wang J, Hanley-Yanez K, Lemster B, Schwisow JA, Ambardekar AV, Degann SH, Bristow MR, Sheppard R, Alexis JD, Tilley DG, Kontos CD, McClung JM, Taylor AL, Yancy CW, Khalili K, Seidman JG, Seidman CE, McTiernan CF, Cheung JY, Feldman AM.
JAMA Cardiol. 2018 Oct 1;3(10):929-938. doi: 10.1001/jamacardio.2018.2541.
PMID: 30140897

Filamin C Truncation Mutations Are Associated With Arrhythmogenic Dilated Cardiomyopathy and Changes in the Cell-Cell Adhesion Structures.

Begay RL, Graw SL, Sinagra G, Asimaki A, Rowland TJ, Slavov DB, Gowan K, Jones KL, Brun F, Merlo M, Miani D, Sweet M, Devaraj K, Wartchow EP, Gigli M, Puggia I, Salcedo EE, Garrity DM, Ambardekar AV, Buttrick P, Reece TB, Bristow MR, Saffitz JE, Mestroni L, Taylor MRG.
JACC Clin Electrophysiol. 2018 Apr;4(4):504-514. doi: 10.1016/j.jacep.2017.12.003. Epub 2018 Feb 2.
PMID: 30067491

Entrepreneurialism in the Translational Biologic Sciences: Why, How, and However.

Bristow MR, Leinwand LA, Olson EN. JACC Basic Transl Sci. 2018 Mar 1;3(1):1-8. doi: 10.1016/j.jacbts.2017.10.004. eCollection 2018 Feb.
PMID: 30062188

A genotype-directed comparative effectiveness trial of Bucindolol and metoprolol succinate for prevention of symptomatic atrial fibrillation/atrial flutter in patients with heart failure: Rationale and design of the GENETIC-AF trial.

Piccini JP, Connolly SJ, Abraham WT, Healey JS, Steinberg BA, Al-Khalidi HR, Dignacco P, van Veldhuisen DJ, Sauer WH, White M, Wilton SB, Anand IS, Dufton C, Marshall DA, Aleong RG, Davis GW, Clark RL, Emery LL, Bristow MR. Am Heart J. 2018 May;199:51-58. doi: 10.1016/j.ahj.2017.12.001. Epub 2017 Dec 6.
PMID: 29754666 

Changing the Research Culture in the United States.

O'Connor CM, Bristow MR. JACC Heart Fail. 2018 Apr;6(4):344-345. doi: 10.1016/j.jchf.2018.03.001. No abstract available.
PMID: 29598937

Improving Heart Failure Therapeutics Development in the United States: The Heart Failure Collaboratory.

O'Connor CM, Psotka MA, Fiuzat M, Lindenfeld J, Abraham WT, Bristow MR, Canos D, Harrington RA, Hillebrenner M, Jessup M, Malik FI, Solomon SD, Stockbridge N, Tcheng JE, Unger EF, Whellan DJ, Zuckerman B, Califf RM. J Am Coll Cardiol. 2018 Jan 30;71(4):443-453. doi: 10.1016/j.jacc.2017.11.048. Review. 
PMID: 29389362

Contractile reserve and the response to cardiac resynchronization therapy.

Bristow MR. Int J Cardiol. 2018 Feb 1;252:234-235. doi: 10.1016/j.ijcard.2017.11.014. No abstract available.
PMID: 29249434

Histamine H2 Receptor Polymorphisms, Myocardial Transcripts, and Heart Failure (from the Multi-Ethnic Study of Atherosclerosis and Beta-Blocker Effect on Remodeling and Gene Expression Trial).

Leary PJ, Kronmal RA, Bluemke DA, Buttrick PM, Jones KL, Kao DP, Kawut SM, Krieger EV, Lima JA, Minobe W, Ralph DD, Tedford RJ, Weiss NS, Bristow MR. 
Am J Cardiol. 2018 Jan 15;121(2):256-261. doi: 10.1016/j.amjcard.201 7.10.016. Epub 2017 Oct 20.
PMID: 29191567

2017

Structural and Functional Phenotyping of the Failing Heart: Is the Left Ventricular Ejection Fraction Obsolete?

Bristow MR, Kao DP, Breathett KK, Altman NL, Gorcsan J 3rd, Gill EA, Lowes BD, Gilbert EM, Quaife RA, Mann DL. JACC Heart Fail. 2017 Nov;5(11):772-781. doi: 10.1016/j.jchf.2017.09.009. Review.
PMID: 29096787

Heart Rate in Preserved Ejection Fraction Heart Failure.

Bristow MR, Altman NL. JACC Heart Fail. 2017 Nov;5(11):792-794. doi: 10.1016/j.jchf.2017.09.004. Epub 2017 Oct 11. No abstract available. PMID: 29032133

MicroRNAs in Heart Failure, Cardiac Transplantation, and Myocardial Recovery: Biomarkers with Therapeutic Potential.

Shah P, Bristow MR, Port JD. Curr Heart Fail Rep. 2017 Dec;14(6):454-464. doi: 10.1007/s11897-017-0362-8. Review. PMID: 28940102

Outcomes of cardiac resynchronization therapy in patients with intermittent atrial fibrillation or atrial flutter in the COMPANION trial.

Kalscheur MM, Saxon LA, Lee BK, Steinberg JS, Mei C, Buhr KA, DeMets DL, Bristow MR, Singh SN.
Heart Rhythm. 2017 Jun;14(6):858-865. doi: 10.1016/j.hrthm.2017.03.024. Epub 2017 Mar 18.
PMID: 28323173

Genetic variation expressed in the brain may impact heart failure.

Bristow MR.Eur J Heart Fail. 2017 Mar;19(3):324-325. doi: 10.1002/ejhf.745. No abstract available.
PMID: 28251773

Myocardial microRNAs associated with reverse remodeling in human heart failure.

Sucharov CC, Kao DP, Port JD, Karimpour-Fard A, Quaife RA, Minobe W, Nunley K, Lowes BD, Gilbert EM, Bristow MR. JCI Insight. 2017 Jan 26;2(2):e89169. doi: 10.1172/jci.insight.89169.
PMID: 28138556

2016

Fine Tuning Adenylyl Cyclase as a (Gene) Therapy for Heart Failure.

Port JD, Bristow MR. JACC Basic Transl Sci. 2016 Dec 26;1(7):630-632. doi: 10.1016/j.jacbts.2016.10.005. eCollection 2016 Dec. No abstract available.
PMID: 30167546

Data and Safety Monitoring Board evaluation and management of a renal adverse event signal in TOPCAT.

Bristow MR, Sharma K, Assmann SF, Linas S, Gersh BJ, Grady C, Rice MM, Singh S, Boineau R, McKinlay SM, Greenberg BH. Eur J Heart Fail. 2017 Apr;19(4):457-465. doi: 10.1002/ejhf.686. Epub 2016 Nov 21. PMID: 27873428

Reply: Is Histamine H2 Receptor a Real Promising Target for Prevention or Treatment of Heart Failure?

Leary PJ, Bristow MR. J Am Coll Cardiol. 2016 Nov 1;68(18):2029-2030. doi: 10.1016/j.jacc.2016.07.774. No abstract available.
PMID: 27788859

Detection and Management of Geographic Disparities in the TOPCAT Trial: Lessons Learned and Derivative Recommendations.

Bristow MR, Enciso JS, Gersh BJ, Grady C, Rice MM, Singh S, Sopko G, Boineau R, Rosenberg Y, Greenberg BH. JACC Basic Transl Sci. 2016 Apr;1(3):180-189.
PMID: 27747305

Lessons Learned and Insights Gained in the Design, Analysis, and Outcomes of the COMPANION Trial.

Bristow MR, Saxon LA, Feldman AM, Mei C, Anderson SA, DeMets DL.

JACC Heart Fail. 2016 Jul;4(7):521-535. doi: 10.1016/j.jchf.2016.02.019. Epub 2016 Jun 8. Review. Erratum in: JACC Heart Fail. 2017 Jan;5(1):75-79.
PMID: 27289408

Histamine H2 Receptor Antagonists, Left Ventricular Morphology, and Heart Failure Risk: The MESA Study.

Leary PJ, Tedford RJ, Bluemke DA, Bristow MR, Heckbert SR, Kawut SM, Krieger EV, Lima JA, Masri CS, Ralph DD, Shea S, Weiss NS, Kronmal RA. J Am Coll Cardiol. 2016 Apr 5;67(13):1544-1552. doi: 10.1016/j.jacc.2016.01.045.
PMID: 27150686

2015

Sex-related differences in age-associated downregulation of human ventricular myocardial β1-adrenergic receptors.

Lindenfeld J, Cleveland JC Jr, Kao DP, White M, Wichman S, Bristow JC, Peterson V, Rodegheri-Brito J, Korst A, Blain-Nelson P, Sederberg J, Hunt SA, Gilbert EM, Ambardekar AV, Minobe W, Port JD, Bristow MR. J Heart Lung Transplant. 2016 Mar;35(3):352-361. doi: 10.1016/j.healun.2015.10.021. Epub 2015 Oct 19.
PMID:26970472

The adrenergic system in pulmonary arterial hypertension: bench to bedside (2013 Grover Conference series).

Bristow MR, Quaife RA. Pulm Circ. 2015 Sep;5(3):415-23. doi: 10.1086/682223. Review.
PMID: 26401244

Visual analysis of biological data-knowledge networks.

Vehlow C, Kao DP, Bristow MR, Hunter LE, Weiskopf D, Görg C.
BMC Bioinformatics. 2015 Apr 29;16:135. doi: 10.1186/s12859-015-0550-z.
PMID: 25925016

Cardiovascular drug development: is it dead or just hibernating?

Fordyce CB, Roe MT, Ahmad T, Libby P, Borer JS, Hiatt WR, Bristow MR, Packer M, Wasserman SM, Braunstein N, Pitt B, DeMets DL, Cooper-Arnold K, Armstrong PW, Berkowitz SD, Scott R, Prats J, Galis ZS, Stockbridge N, Peterson ED, Califf RM. J Am Coll Cardiol. 2015 Apr 21;65(15):1567-82. doi: 10.1016/j.jacc.2015.03.016. Review.
PMID: 25881939

Therapeutic Molecular Phenotype of β-Blocker-Associated Reverse-Remodeling in Nonischemic Dilated Cardiomyopathy.

Kao DP, Lowes BD, Gilbert EM, Minobe W, Epperson LE, Meyer LK, Ferguson DA, Volkman AK, Zolty R, Borg CD, Quaife RA, Bristow MR. Circ Cardiovasc Genet. 2015 Apr;8(2):270-83. doi: 10.1161/CIRCGENETICS.114.000767. Epub 2015 Jan 30.
PMID: 25637602

Peax: interactive visual analysis and exploration of complex clinical phenotype and gene expression association.

Hinterberg MA, Kao DP, Bristow MR, Hunter LE, Port JD, Görg C. Pac Symp Biocomput. 2015:419-30.
PMID: 25592601

Genetic variants are not associated with outcome in patients with coronary artery disease and left ventricular dysfunction: results of the Genetic Substudy of the Surgical Treatment for Ischemic Heart Failure (STICH) trials.

Feldman AM, She L, McNamara DM, Mann DL, Bristow MR, Maisel AS, Wagner DR, Andersson B, Chiariello L, Hayward CS, Hendry P, Parker JD, Racine N, Selzman CH, Senni M, Stepinska J, Zembala M, Rouleau J, Velazquez EJ, Lee KL. Cardiology. 2015;130(2):69-81. doi: 10.1159/000368221. Epub 2015 Jan 13.
PMID: 25592552

 

 

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